embolizare splenica partiala

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AJR:195 , November 2010 1241

persists for more than 1 week [1]. This report

describes the hematologic response and clini-

cal outcome of use of the Onyx liquid embo-

lization system (ev3) for partial splenic embo-

lization to increase the platelet counts of three

oncology patients before administration of

systemic chemotherapy.

Subjects and Methods

Approval for this report was obtained from our

institutional review board. Between December

2008 and February 2009, we performed partial

splenic embolization with the Onyx-18 liquid em-

bolization system to treat three oncology patients

with cirrhosis and hypersplenism. This emboliza-

tion agent is made of 6% ethylene vinyl alcohol

copolymer dissolved in dimethyl sulfoxide, which

is suspended in a micronized tantalum powder to

provide contrast for visualization under fluorosco-

py. The off-label use of the agent was discussed

with all patients at initial consultation. All three

patients had thrombocytopenia (Table 1) prevent-

ing the initiation or continuation of systemic che-motherapy treatments. The three patients were a

61-year-old woman with stage IV rectal carcino-

ma in whom sinusoidal obstruction syndrome de-

veloped after oxaliplatin therapy and 46-year-old

and 64-year-old men with multifocal metastatic

hepatocellular carcinoma due to cirrhosis second-

ary to hepatitis C infection.

All patients underwent contrast-enhanced ab-

dominal CT before partial splenic embolization

and underwent follow-up CT 13 months after the

Management of Hypersplenism byPartial Splenic Embolization WithEthylene Vinyl Alcohol Copolymer

Carin F. Gonsalves1

Edith P. Mitchell2

Daniel B. Brown1

Gonsalves CF, Mitchell EP, Brown DB

1Department of Radiology, Division of Interventional

Radiology, Thomas Jefferson University Hospital, 132 S10th St., Main Bldg., Ste. 766, Philadelphia, PA 19107.

Address correspondence to C. F. Gonsalves

([email protected]).

2Department of Medical Oncology, Thomas Jefferson

University Hospital, Philadelphia, PA.

Vascular and Interventional Radiolog y Technical Innovation

AJR2010; 195:12411244

0361803X/10/19551241

American Roentgen Ray Society

Thrombocytopenia related to hy-

persplenism is seen in a variety of

clinical settings, the most com-

mon being portal hypertension

due to cirrhosis [1]. For oncology patients,

thrombocytopenia can preclude or limit ad-

ministration of systemic chemotherapy. Al-

though hematopoietic growth factors such as

erythropoietin and granulocyte colony-stimu-

lating factor can be used to increase RBC and

granulocyte production, respectively, platelet

transfusion continues to be the most effective

method of correcting thrombocytopenia. An

increase in platelet sequestration and destruc-

tion, however, renders platelet transfusion a

temporary and impractical solution for pa-

tients with hypersplenism.

For more than 20 years, partial splenic em-

bolization has been used to treat patients with

hypersplenism. Although the efficacy of par-

tial splenic embolization for relieving throm-

bocytopenia is well-established, a review of

the literature from 1973 to 2005 showed thatan optimal embolic agent had not been de-

fined [13]. Various embolic materials have

been used for partial splenic embolization, in-

cluding temporary agents such as absorbable

gelatin sponge (Gelfoam, Pfizer) and perma-

nent agents such as polyvinyl alcohol (PVA)

particles and stainless steel coils. All of these

agents, however, are associated with a postem-

bolization syndrome characterized by a com-

bination of pain, fever, and pleurisy that often

Keywords:Onyx liquid embolization system, partial

splenic embolization, thrombocytopenia

DOI:10.2214/AJR.10.4401

Received February 5, 2010; accepted after revision

March 26, 2010.

OBJECTIVE.Partial splenic embolization has been used for more than 20 years to manage

thrombocytopenia secondary to hypersplenism. Both temporary and permanent embolic agents

have been used without definition of an optimal agent. The purposes of this report are to de-

scribe the use of the Onyx nonadhesive liquid embolization system to treat three patients with

severe hypersplenism precluding administration of systemic chemotherapy and to report on the

hematologic response and clinical outcome after partial splenic embolization with this agent.

CONCLUSION.The platelet counts of three patients treated by partial splenic emboliza-tion with the Onyx agent improved sufficiently for administration of systemic chemotherapy.

In addition, severe postembolization syndrome, a common occurrence after partial splenic em-

bolization, did not occur in our patient population.

Gonsalves et al.Partial Splenic Embolization for Hypersplenism

Vascular and Interventional RadiologyTechnical Innovation


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1242 AJR:195 , November 2010

Gonsalves et al.

procedure (Fig. 1). Splenic volumes were deter-

mined with National Institutes of Health public

domain image processing and analysis software.

The percentage of splenic infarction was calcu-

lated as infarcted volume divided by total splenic

volume and multiplied by 100 [1].

Platelet counts were performed the morning of

the procedure and weekly until chemotherapy was

initiated (Table 1). Platelet counts after completion

of chemotherapy were recorded when available

(Table 1). Clinical success was defined as an in-crease in platelet count that allowed administration

of chemotherapy. Initiation of systemic chemother-

apy was determined by the treating medical oncol-

ogist and based on platelet count and urgency.

The technique used for partial splenic emboliza-

tion was similar for all three patients. The patient

was given pneumococcal vaccine (Pneumovax,

Merck) and 1 g of cefazolin IV before the proce-

dure. The femoral approach was used for arterial

access to select the splenic artery and perform dig-

ital subtraction angiography to define the splenic

arterial anatomy (Fig. 2A). A 2.7-French dimeth-

yl sulfoxidecompatible microcatheter (Progreat,

Terumo Medical Corporation) was used to select a

branch of the splenic artery, and arteriography was

repeated (Fig. 2B). In two patients (the 46-year-

old man and the 61-year-old woman), the splenic

artery divided into superior and inferior terminal

branches before further dividing into intrasplenic

segmental arterial branches. Partial splenic embo-

lization was accomplished by selection of a termi-nal branch and slow (?0.1 mL/s) injection of the

embolization agent while the catheter was with-

drawn. In the third patient, complex splenic arterial

anatomy necessitated embolization of two splenic

artery branches with a similar technique. Postem-

bolization arteriography was performed from the

main splenic artery (Figs. 2C and 2D). The proce-

dure was terminated when angiography showed an

estimated 4060% of the splenic parenchyma was

successfully embolized.

After partial splenic embolization, initial pain

control was achieved overnight with either a patient-

controlled analgesia pump (hydromorphone hydro-

chloride, Dilaudid, Hospira) (one patient) or oral

analgesics (oxycodone) (two patients). Information

on length of hospital stay after the procedure, hos-

pital readmissions, and complications was obtained

by review of the hospital and outpatient medical re-

cords after revisits to the oncology and intervention-

al radiology clinics. Complications were classified

according to the Society of Interventional Radiology

classification system of complications by outcome.

Results

Partial splenic embolization was techni-

cally and clinically successful in all three pa-

tients. There were no procedural complica-

tions. All three patients were discharged from

the hospital the day after the procedure afe-

brile with normal WBC counts. None of the

three patients reported marked abdominal

pain after t reatment, and none needed narcot-

ic prescriptions at discharge. All patients were

telephoned 57 days after the procedure to

ensure that their condition remained asymp-

tomatic before the 1-month follow-up appoint-

ment in the clinic.

On the basis of the CT findings after em-

bolization, the splenic infarction percentag-

es were 77% in the 61-year-old woman with

rectal carcinoma and 51% and 32% in the 46-

and 64-year-old men with metastatic hepa-

tocellular carcinoma. Thrombocytopenia re-

solved in all three patients, and chemotherapy

was initiated on day 38 for the woman, on day18 for the 46-year-old man, and day 60 for the

64-year-old man. The platelet responses are

shown in Table 1. Sustained platelet counts

were observed in the 61-year-old woman 9

months and the 64-year-old man 16 months

after partial splenic embolization (Table 1).

Discussion

Absorbable gelatin sponge (Gelfoam, Pfiz-

er) is the most commonly described embolic

A

Fig. 161-year-old woman with sinusoidal obstruction syndrome after chemotherapy for stage IV rectalcarcinoma.A,Contrast-enhanced abdominal CT scan shows appearance before partial splenic embolization.

B,Contrast-enhanced abdominal CT scan 1 month after partial splenic embolization shows heterogeneouslyenhancing spleen with areas of infarction (arrow). High-attenuation material (arrowhead) near splenic hilumrepresents liquid embolization agent within splenic artery branches.

B

TABLE 1: Platelet Counts Before and After Partial Splenic Embolization and Percentage of Splenic InfarctionAfter Treatment

Patient

Platelet Count ( 103/L) Splenic Infarction

BeforeEmbolization

1 wk AfterEmbolization

2 wk AfterEmbolization

Immediately BeforeChemotherapy Longest Follow-Up Period %

Time AfterEmbolization (mo)

61-year-old woman 66 98 451 252 (38 d) 313 (9 mo) 77 1

46-year-old man 58 91 112 92 (18 d) Died of tumor progression 38 dafter embolization

51 3

64-year-old man 42 46 77 98 (60 d) 191 (16 mo) 32 1

NoteValues in parentheses are time af ter partial splenic embolization.
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AJR:195 , November 2010 1243

Partial Splenic Embolization for Hypersplenism

material for partial splenic embolization, but

it has been cr iticized, predominantly because

of its temporary nature [2]. In a prospective

randomized comparison of PVA and Gelfoamabsorbable sponge, both embolic agents were

useful for resolving thrombocytopenia [2].

Patients treated with PVA had a significant-

ly better platelet count response after partial

splenic embolization than did those treated

with Gelfoam pledgets. The authors attribut-

ed this difference to more durable and distal

embolization with permanent small PVA par-

ticles (300500 m) than with the temporary

and more proximal occlusion achieved with

Gelfoam pledgets [2]. The same study, how-

ever, showed a significantly larger percent-

age of patients treated with PVA (85.7%) thanthose treated with Gelfoam absorbable sponge

(62.5%) had prolonged and intense abdomi-

nal pain [2]. This finding was attributed to a

greater degree of infarction with the smaller

PVA particles (300500 m) than with the

larger Gelfoam pledgets (typically 12 mm).

Coils also have been used for partial splenic

embolization and are usually positioned in the

proximal aspect of the distal main splenic ar-

tery or within proximal splenic artery branch-

es. This technique has been criticized for the

potential for arterial recanalization beyond

the proximally placed coils, which limits the

long-term effectiveness of partial splenic em-

bolization [2].

Postembolization syndrome consisting of

fever, abdominal pain, nausea, and anorexiaoccurs in most patients who undergo partial

splenic embolization with any of the previ-

ously described embolic agents. NKontchou

et al. [3] reported that 25 of 32 patients expe-

rienced postembolization syndrome lasting

a median of 3 days (range, 140 days) with

use of either PVA or calibrated microspheres

(Embosphere, BioSphere Medical). The me-

dian hospital stay was 14 days (range, 554

days). Kauffman et al. [4] reported that 28

patients underwent partial splenic emboliza-

tion with gelatin sponge material (n= 24) or

a particulate agent (n = 4). All 28 patients

experienced postembolization syndrome af-

ter the procedure and had a median hospital

stay of 4 days (range, 123 days).

Even though our sample size was small,

all three patients reported essentially no

postembolization syndrome, a finding al-

most unheard of in partial splenic emboliza-

tion. Katsanos et al. [5] described a similar

absence of postembolization syndrome af-

ter embolization of a renal angiomyolipoma

with the Onyx liquid embolization system.

The perivascular response to the Onyx ethyl-

ene vinyl alcohol copolymer has been histo-

logically evaluated in resected arteriovenousmalformations. In comparison with cyano-

acrylates [6], the Onyx copolymer was as-

sociated with less severity of inflammatory

change within the vessel wall and no signifi-

cant reaction in the surrounding interstitium.

In a study of swine [7], the perivascular in-

flammatory response after Onyx emboliza-

tion was related to speed of injection. Fast-

er injection was associated with endothelial

necrosis and vascular inflammation, but no

inflammatory changes were found after slow

injection. Our standard practice with the

Onyx system is to slowly inject the emboliza-

tion agent at 0.1 mL/s or less.The ideal extent of splenic parenchymal in-

farction for improvement in hematologic val-

ues remains unknown [13, 8]. Sangro et al.

[8] noted that less than 50% splenic infarction

was associated with a poor hematologic re-

sponse but that 6070% infarction was asso-

ciated with more durable and substantial im-

provement in hematologic values after partial

splenic embolization. Harned et al. [9], how-

A

Fig. 246-year-old man with multifocal metastatic hepatocellular carcinoma resulting from cirrhosissecondary to hepatitis C infection.A,Preembolization arteriogram obtained with 5-French catheter in main splenic artery shows splenic arterydividing into superior (toparrow) and inferior (bottom arrow) terminal branches near splenic hilum.B,Selective arteriogram obtained with 3-French microcatheter positioned in superior terminal branch ofsplenic artery shows appearance before embolization.C, Digital subtraction splenic arteriogram obtained after embolization of approximately 50% of spleen showscast of liquid embolization agent within branches of superior terminal branches (white arrow) of splenic artery.Areas of infarction (blackarrow), evidenced as lack of parenchymal blush, are present in superior aspect ofspleen.D,Nonsubtraction arteriogram of splenic artery shows cast of liquid embolization agent in branches of superior

terminal branch of splenic artery (arrow).

C

B

D
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1244 AJR:195 , November 2010

Gonsalves et al.

ever, observed a hematologic response after

embolization of 3040% of the splenic paren-

chyma, two of five patients maintaining higher

platelet counts for longer than 6 months.

NKontchou et al. [3] evaluated clinical out-

come based on percentage of splenic infarction

after partial splenic embolization and found

that splenic abscess formation and septicemiaresulted in two deaths after embolization of a

large percentage (> 70%) of the splenic paren-

chyma. Therefore, the recommendation in the

literature for extent of splenic embolization

for improvement in hematologic values ranges

from 30% to 70%. However, determination of

the true target volume of embolized spleen

with single planar angiography remains a

challenge for interventional radiologists, and

the situation is no different for partial splenic

embolization with the Onyx liquid embolization

system. Use of C-arm CT angiography to ac-

quire multiplanar information on the soft-tis-

sue parenchyma may facilitate estimation of tar-

get volume during partial splenic embolization.

Improvement in platelet count after par-

tial splenic embolization may be seen within

1224 hours after the procedure but usually

reaches a peak value 12 weeks after treat-

ment [1]. After partial splenic embolization,

the platelet count typically stabilizes within

2 months at a level twofold higher than the

preprocedure value [1]. Our three patients

achieved adequate platelet counts after par-

tial splenic embolization and underwent sys-

temic chemotherapy within 60 days after the

procedure. Platelet counts were sustained in

the two patients who survived to participate

in long-term follow-up (Table 1).

Partial splenic embolization with the Onyx-

18 liquid embolization system resulted in suffi-cient improvement in the platelet count for ad-

ministration of systemic chemotherapy to the

three patients in our sample. Platelet counts

also were normal in long-term follow-up. The

most promising outcome we encountered, how-

ever, was the lack of severe postembolization

syndrome after partial splenic embolization.

Further investigation is warranted to determine

whether our results are reproducible in a larger

group of patients. If so, Onyx copolymer may

prove to be the preferable agent for partial

splenic embolization.

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1. Amr A. Nassef, Ayman A. Zakaria, Mohamed S. Abd ElBary. 2013. Partial splenic artery embolization in portal hypertensionpatients with hypersplenism: Two interval-spaced sessions technique. The Egyptian Journal of Radiology and Nuclear Medicine

44:3, 531-537. [CrossRef]

2. Ming-Ching Ou, Ming-Tsung Chuang, Xi-Zhang Lin, Hong-Ming Tsai, Shu-Yuan Chen, Yi-Sheng Liu. 2013. A novelmethod for the angiographic estimation of the percentage of spleen volume embolized during partial splenic embolization.

European Journal of Radiology82:8, 1260-1265. [CrossRef]3. W.A. Wohlgemuth, W. Uller, R. Mller-Wille. 2013. Flssigembolisate Onyx als Problemlser. Der Radiologe53:3, 223-229.

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embolizare splenica partiala