BRIEF REPORT

Prophylactic Topically Applied Ice to PreventCutaneous Complications of Nontarget

Chemoembolization and Radioembolization

David S. Wang, MD, John D. Louie, MD, Nishita Kothary, MD,Rajesh P. Shah, MD, and Daniel Y. Sze, MD, PhD

ABSTRACT

Cutaneous complications can result from nontarget deposition during transcatheter arterial chemoembolization or radioembolization.

Liver tumors may receive blood supply from parasitized extrahepatic arteries (EHAs) that also perfuse skin or from hepatic arteries

located near the origin of the falciform artery (FA), which perfuses the anterior abdominal wall. To vasoconstrict cutaneous

vasculature and prevent nontarget deposition, ice packs were topically applied to at-risk skin in nine chemoembolization treatments

performed via 14 parasitized EHAs, seven chemoembolization treatments near the FA origin, and five radioembolization treatments in

cases in which the FA could not be prophylactically coil-embolized. No postprocedural cutaneous complications were encountered.

ABBREVIATIONS

EHA = extrahepatic artery, FA = falciform artery, HCC = hepatocellular carcinoma, ICA = intercostal artery, IMA = internalmammary artery, IPA = inferior phrenic artery

Transcatheter arterial chemoembolization and radioemboliza-

tion are technically demanding locoregional palliative treat-

ment options for primary liver tumors and liver-dominant

metastatic disease. Although uncommon, cutaneous complica-

tions from chemoembolization or radioembolization include

rash, pain, induration, ulceration, and necrosis caused by

nontarget delivery of chemoembolic agents or yttrium-90

(90Y) microspheres to terminal arterial branches supplying

skin (1,2).

Skin complications from transcatheter arterial therapies

are of particular concern in two scenarios. First, liver

tumors, especially if peripherally located or large, can

develop collateral blood supply parasitized from extrahepa-

tic arteries (EHAs) in 17%–27% of patients (3,4). Trans-

catheter arterial chemoembolization through parasitized

EHAs has been demonstrated to be an effective treatment

to control hepatic tumors (3–6), but may result in cutaneous

& SIR, 2013

J Vasc Interv Radiol 2013; 24:596–600

http://dx.doi.org/10.1016/j.jvir.2012.12.020

From the SIR 2012 Annual Meeting.

None of the authors have identified a conflict of interest.

From the Division of Interventional Radiology, Department of Radiology,

Stanford University Medical Center, 300 Pasteur Drive, H3630, Stanford, CA

94305-5642. Received November 12, 2012; final revision received and

accepted December 21, 2012. Address correspondence to D.S.W.; E-mail:

dwang@stanfordmed.org

complications when involving the intercostal artery (ICA)

(1,5), internal mammary artery (IMA) (1,4,6), or inferior

phrenic artery (IPA) (7). Second, the falciform artery (FA),

which is visualized in 2%–25% of angiographic studies,

arises as a branch of the left or middle hepatic artery,

courses through the falciform ligament, and provides blood

supply to the anterior abdominal wall between the xiphoid

process and umbilicus (8). Administration of chemoembolic

agents (8,9) or 90Y microspheres (2,10) proximal to or in

proximity to the FA can result in skin complications. If the

FA is identified prospectively, prophylactic coil emboliza-

tion can be performed before chemoembolization (11) or

radioembolization (2,10), but this may not be possible if the

FA is diminutive or tortuous.

In such situations in which there was a recognized risk

for cutaneous complications, we applied topical ice packs

to the skin region susceptible to nontarget deposition to

induce vasoconstriction of the cutaneous vasculature (12)

and to limit dermal injury. We retrospectively studied the

outcomes after use of this simple adjunctive maneuver.

MATERIALS AND METHODS

Institutional review board approval was granted for this

retrospective study. All data were managed in accordance

with the Health Insurance Portability and Accountability

Act. A keyword database search of the radiology informatics

system was performed to identify chemoembolization and

Figure 1. Images from a 65-year-old patient with HCC andresidual viable tumor in the anterolateral right hepatic lobe afterprevious transcatheter arterial chemoembolization. (a) Arterio-gram of the right 10th ICA revealed parasitized EHAs supplyinghypervascular tumor in the liver (arrows). Chemoembolizationwas performed via a microcatheter positioned near the origin ofthese parasitized branches, without topical application of icepacks. (b) Postembolization arteriogram showed stasis in theparasitized EHAs and avid uptake of chemoembolic emulsion(asterisk) and marked increase in prominence of musculocuta-neous chest wall branches (arrows), the normal and onlyresidual outflow of the ICA. This patient developed a painfulskin rash along the lateral right chest wall 2 days after theprocedure.

Table 1 . Demographic and Treatment Details of ProceduresPerformed with Topical Ice Packs Applied to At-risk SkinTerritories

Characteristic Value

Per patient (N ¼ 19)

Age (y)

Volume 24 ’ Number 4 ’ April ’ 2013 597

radioembolization procedures performed from October 2000

to October 2012 in which ice was topically applied.

Procedural digital subtraction angiography and cone-beam

C-arm computed tomography (CT) images and medical

records were retrospectively reviewed. Transcatheter arterial

chemoembolization and radioembolization techniques have

been previously described (13,14). Cone-beam C-arm CT

has been used routinely in these procedures since

March 2007.

In patients with parasitized EHAs, tumors were treated

with only chemoembolization, whereby chemoembolic mate-

rials were superselectively delivered directly into the EHAs

via a microcatheter. Chemoembolic materials consisted of

doxorubicin and/or cisplatinum solutions emulsified with

ethiodized oil (Ethiodol; Savage Laboratories, Melville,

New York; or Lipiodol; Guerbet, Villepinte, France), with

gelatin foam slurry or particulate embolic agents added when

arterioportal or arteriovenous shunting was detected; or drug-

eluting beads (100–300-mm LC Bead loaded with doxorubi-

cin; Biocompatibles, Oxford, Connecticut). The suspected

parasitized EHA was first evaluated by digital subtraction

angiography and/or contrast-enhanced cone-beam C-arm CT

imaging. If cutaneous branches originating from the EHA

were identified and the best achieved microcatheter position

for planned delivery was still deemed to present high risk

for nontarget embolization (Fig 1), plastic bags of crushed

or small cubed ice were topically applied to the skin in

the distribution of the identified cutaneous branches at least

10 minutes before and during transcatheter administration of

the chemoembolic materials. Arteriography was repeated

after topical application of ice and before chemoembolization

to assess for vasoconstriction.

In chemoembolization and radioembolization procedures

in which the FA was visualized angiographically and

susceptible to nontarget delivery but could not be prophy-

lactically coil-embolized, ice packs were applied to the

supraumbilical anterior abdominal wall in an identical

fashion before administration of chemoembolic materials

or 90Y microspheres (SIR-Sphere; Sirtex Medical, Lane

Cove, Australia; or TheraSphere; Nordion, Ottawa, Ontario,

Canada).

Mean 58.7

Range 41–79

Sex

Male 13 (68.4)

Female 6 (31.6)

Liver tumor type

Hepatocellular carcinoma 15 (82.4)

Metastases (colorectal, thyroid, renal carcinoma) 4 (17.6)

Per procedure (N ¼ 21)

Chemoembolization

Parasitized extrahepatic arteries 9 (47.4)

Segment 4 arteryn 7 (31.6)

Radioembolization of LHA/segmental branchn 5 (21.1)

Values in parentheses are percentages.LHA ¼ left hepatic artery.n Falciform artery not prophylactically embolized.

RESULTS

Prophylactic topical application of ice packs was used to

prevent cutaneous complications in 16 transcatheter arterial

chemoembolization and five radioembolization procedures

in 19 patients (two underwent chemoembolization with

topical ice packs twice; Table 1). Mean patient age was

58.7 years (range, 41–79 y); 13 (68%) were men. Fifteen

patients (79%) were treated for hepatocellular carcinoma

(HCC) and the remaining four were treated for hepatic

metastases.

Nine procedures were transcatheter arterial chemoembo-

lization treatments delivered through 14 parasitized EHAs.

Parasitized EHAs included the right ICA (n ¼ 8; T8 to

Figure 2. Images from a 51-year-old patient with HCC andresidual viable tumor along the lateral aspect of a segment6 lesion previously treated with transcatheter arterial chemoem-bolization. (a) Arteriogram of the right 11th ICA demonstrateda parasitized EHA supplying hypervascular tumor (arrow).(b) Fluoroscopic image after chemoembolization performedwith topical application of ice packs (note diffuse artifact) andthe microcatheter advanced into the parasitized branch vesselshowed uptake by the lesion (arrow). A static column ofcontrast medium was seen within a superficial side-branchvessel (arrowhead), reflecting hypothermia-induced vasocon-striction. This patient experienced no cutaneous complications.

Wang et al ’ JVIR598 ’ Ice to Prevent Cutaneous Complications of Nontarget Embolization

T11; Fig 2), right IMA (n ¼ 3; Fig 3), right IPA (n ¼ 2),

and left IMA (n ¼ 1; Table 2). These patients had

undergone an average of 3.6 previous chemoemboliza-

tions (range, two to six). Two patients exhibited occlusion

or severe attenuation of the hepatic arteries from previous

treatments.

Of the 12 cases in which the FA was visualized (Fig 4) but

prophylactic coil embolization was not feasible, seven were

chemoembolization procedures in which chemoembolic

agents were delivered in close proximity to the FA origin

and five were radioembolization administrations (SIR-

Sphere, n ¼ 3; TheraSphere, n ¼ 2) via the left hepatic

artery or a segmental branch proximal to the FA. As

comparison, prophylactic embolization of the FA was

successful in 20 chemoembolization or radioembolization

procedures performed during the same period of review.

Median follow-up was 5.7 months (range, 1.7–20.9 mo).

A minimum of 6 weeks follow-up—the period during

which cutaneous complications would be expected to

manifest—was obtained for all patients. Review of medical

records revealed no cutaneous complications in any patient.

All patients tolerated topical application of ice, but a few

required additional intravenous sedative medications

because of the discomfort caused by the cold ice. There

were no hypothermia-related adverse reactions, and

patients were kept warm and sedated enough to avoid

shivering and motion degradation of intraprocedural

imaging.

In the nine chemoembolization treatments of parasitized

EHAs in which skin-supplying vessels were identified,

arteriography performed after topical application of ice

demonstrated slower flow or stasis in superficial cutaneous

vessels and decreased body wall enhancement, with pre-

servation of flow into deeper parasitized arteries supplying

tumor (Fig 2b). Completion unenhanced cone-beam C-arm

CT was performed in 13 of the 16 chemoembolization

procedures; none showed evidence of nontarget uptake in

the at-risk skin or subcutaneous tissues (Fig 3c).

DISCUSSION

The principal technical objective of transcatheter arterial

interventions for hepatic malignancies is to deliver cyto-

toxic or radioactive agents selectively to tumors while

minimizing deposition in adjacent nonmalignant hepatic

and extrahepatic tissues. Safe and complete treatment

typically requires detailed angiographic evaluation of the

arterial pathways, use of microcatheters for superselective

catheterization of specific tumor-feeding arteries, and care-

ful administration of the therapeutic agents under vigilant

fluoroscopic monitoring to detect and prevent reflux.

Cutaneous complications can occur when the therapeutic

agents are delivered through or in proximity to an artery

that normally provides branches supplying skin and there is

inadvertent deposition in the terminal cutaneous branches

(1,2). Skin injury is thought to be caused by direct dermal

exposure to chemotherapeutic drugs or to b-irradiation,

possibly exacerbated by ischemia (1,9,10). Most skin

complications are mild and transient, and can be treated

with topical agents such as silver-containing ointments or

local corticosteroid injections. More severe complications

may present as fat and dermal necrosis and ulceration,

which may be complicated by infection. These severe cases

may require surgical debridement and/or skin grafting

(1,4,10).

Cutaneous complications can occur following trans-

catheter arterial chemoembolization of parasitized EHAs

originating from the ICA (1,5), IMA (1,4,6), and IPA (7),

as well as transcatheter arterial chemoembolization (8,9)

and radioembolization procedures (2,10) in which delivery

is performed proximal or in proximity to a patent FA. We

have described a simple, safe, and inexpensive method that

may reduce the risk of cutaneous nontarget chemoembo-

lization and radioembolization by using local hypothermia

to induce vasoconstriction of the superficial cutaneous

vasculature (12). Angiography confirmed decreased flow

into the at-risk skin, and completion cone-beam C-arm CT

showed no deposition of radiopaque agents in the at-risk

territories. On follow-up, there were no cutaneous compli-

cations following these high-risk procedures.

Although the present study did not have a control arm,

historical published data show that skin necrosis or

erythema occurred in 16.7% of patients who underwent

chemoembolization via parasitized ICAs (5) and in 8.9% of

patients who underwent chemoembolization via parasitized

IMAs (6). Although the right IPA is the most common

Figure 3. Images from a 54-year-old patient with medullary thyroid carcinoma and hepatic metastases supplied by parasitized EHAs.(a) Arteriogram of right IMA revealed multiple parasitized EHAs supplying several intrahepatic hypervascular tumors (arrows).(b) Maximum-intensity projection image reconstructed from cone-beam C-arm CT with contrast medium administered via the rightIMA demonstrated arterial supply to hypervascular lesions in the anterior right lobe (asterisk) and prominent branches supplying theright breast (arrow). Superselective transcatheter arterial chemoembolization was performed with topical ice packs applied to the rightbreast and anterior chest wall. (c) Maximum-intensity projection image reconstructed from completion unenhanced cone-beam C-armCT showed no uptake of the ethiodized oil emulsion in the right breast and overlying skin. This patient showed no symptoms ofcutaneous or chest wall deposition.

Volume 24 ’ Number 4 ’ April ’ 2013 599

source of parasitized collateral vessels to supply liver

tumors (3), to our knowledge, only one case of skin

complication following chemoembolization has been

reported (7). Although the IPA predominantly supplies

the diaphragm, it also provides branches that anastomose

with the ICA and IMA, which may allow for inadvertent

shunting of chemoembolic agents to the skin.

Just as individual parasitized branches supplying tumors

may be too small to select with microcatheters for

superselective treatment, cutaneous branches may also be

too numerous or small to coil or bland embolize for

prophylaxis. Some authors advocate for bland embolization

of parasitized EHAs as a safer alternative to chemoembo-

lization (4,6), particularly when superselective catheteriza-

tion of the tumor-supplying collateral vessels is not

possible. Our method of using topical ice packs to prevent

cutaneous complications may allow for safer use of

cytotoxic agents to exploit their possible improved efficacy.

Table 2 . Distribution of Parasitized EHAs Treated withChemoembolization with Ice Packs Applied (n ¼ 14)

Parasitized EHA Treated Arteries

Right intercostal artery 8 (57.1)

T8 2

T9 3

T10 1

T11 2

Right IMA 3 (21.4)

Right IPA 2 (14.3)

Left IMA 1 (7.1)

Values in parentheses are percentages.EHA ¼ extrahepatic artery, IMA ¼ internal mammary artery,IPA ¼ inferior phrenic artery.

Wang et al ’ JVIR600 ’ Ice to Prevent Cutaneous Complications of Nontarget Embolization

Another potential indication for the topical application

of ice is during chemoembolization or radioembolization

administration when there is a patent FA that cannot be

prophylactically embolized, which may result in nontarget

deposition in the anterior abdominal wall. The FA origin

may be tortuous, diminutive, duplicated, or even a diffuse

network, precluding selective catheterization and prophy-

lactic embolization. Although there is near-consensus in

favor of prophylactic microcoil embolization of a visua-

lized FA before radioembolization (2), prophylactic

embolization of a patent FA before chemoembolization

remains controversial because severe complications are

uncommon (15).

Limitations of the present retrospective study include

the small sample size and absence of a control group

Figure 4. Image from a 60-year-old patient with focal HCC inthe dome of segment 4a. Three-dimensional volume surfacerendering of cone-beam C-arm CT with contrast mediuminjected into the proper hepatic artery showed the segment 4atumor (arrowhead). The FA originated from the segment 4aartery and coursed toward the midline anterior abdomen(arrow). Its origin was extremely tortuous in this patient withcirrhosis and could not be catheterized for prophylactic coilembolization. Ice packs were topically applied as a chemother-apy–ethiodized oil emulsion was delivered just distal to the FAorigin. No cutaneous complications resulted.

for comparison. In addition, criteria for when to apply

ice and what was considered to represent high risk

for cutaneous complications were not prospectively or

strictly defined.

In conclusion, topical application of ice packs to

vasoconstrict superficial arterial branches when the skin

is susceptible to nontarget deposition of chemoembolic

agents or 90Y microspheres may provide an additional

measure of safety in the prevention of cutaneous complica-

tions. It should be considered specifically when transcath-

eter arterial chemoembolization is performed through

parasitized EHAs involving the ICA, IMA, and IPA, and

in chemoembolization and radioembolization administra-

tions in which a patent FA is visualized and cannot be

prophylactically embolized.

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