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Ethanol and Polyvinyl Alcohol Mixture for Transcatheter Embolization of Renal Angiomyolipoma

Uri Rimon, Mordechai Duvdevani, Alexander Garniek, Gil Golan, Paul Bensaid, Jacob Ramon and Benyamina Morag


Renal angiomyolipoma (AML) is a benign hamartomatous tumor that contains fat, smooth muscle, and abnormal blood vessels in varying proportions. Two types of AML are commonly recognized. The sporadic type, a single tumor, occurs mainly in the older population (50-80 years), is predominant among women, and constitutes 80% of all cases of AML. The second type of AML is associated with tuberous sclerosis (TS) and other types of phakomatosis and also is predominant among women. The TS type usually is symptomatic with multiple bilateral lesions and constitutes 20% of all cases of renal AML [1-3].

The main complication of AML is retroperitoneal bleeding, which can be life threatening [1, 3, 4]. The bleeding tendency originates from the irregular, aneurysmal, tortuous blood vessels that constitute the angiogenic component of the tumor [5-7]. The larger the tumor, the greater is the risk of bleeding; 4 cm is the usually accepted cutoff size [3, 8-10]. It is generally agreed that patients with asymptomatic AML larger than 4 cm should be treated, as should those with symptomatic lesions of any size [5, 11]. Nephron-sparing procedures such as tumorectomy and selective embolization are the procedures of choice for preserving the renal parenchyma [1]. Absolute ethanol with or without lipiodol [4, 7, 12-14], coils [6, 13], polyvinyl alcohol (PVA) [6, 13], or gelatin sponge (Gelfoam) [13] has been used successfully as an embolization material. Ethanol is superior to other materials because of its liquidity and high occlusion potential [4, 7, 15].

We made a mixture of the smallest PVA particles available and 96% ethanol to achieve better immediate and long-term occlusion. The purpose of this study was to show the immediate and midterm effects of embolization with a mixture of ethanol and PVA as a permanent obliterator of the angiogenic component of renal AML.

Fig. 1A.

35-year-old man with intrarenal bleeding in large angiomyolipoma of left kidney. Early phase anteroposterior digital subtraction angiogram before embolization shows hypervascular angiogenic component (short arrows) with 4-cm aneurysm (star) with single feeder vessels (long arrow).

Fig. 1B.

35-year-old man with intrarenal bleeding in large angiomyolipoma of left kidney. Late phase of A shows hypervascular angiogenic component (arrows) and 4-cm aneurysm (star). Complete embolization was achieved (not shown).

Fig. 1C.

35-year-old man with intrarenal bleeding in large angiomyolipoma of left kidney. Angiogram shows selective catheterization of aneurysm feeder. Minicoil embolization was performed (not shown).

Fig. 1D.

35-year-old man with intrarenal bleeding in large angiomyolipoma of left kidney. Anteroposterior angiogram 18 months after embolization shows new aneurysm (star) and recurrence of hypervascular but smaller angiogenic component (arrows). Second embolization was performed.

Fig. 1E.

35-year-old man with intrarenal bleeding in large angiomyolipoma of left kidney. Anteroposterior angiogram after third embolization (29 months after first embolization) shows marked reduction in angiogenic component.

Materials and Methods


Institutional review board approval was obtained, and informed consent was waived for this retrospective study, although informed consent had been obtained from each patient before the procedures. From January 1992 to December 2004, 29 patients were referred for angiography and possible embolization of symptomatic or large (> 4 cm) renal AML; there was only one patient from 1992-1996. After embolization, that patient had an elective nephrectomy of the treated kidney because the urologists did not trust the longevity of the embolization. As a result, the actual study follow-up period was 8 years. Among this group, 23 patients underwent therapeutic transcatheter embolization with the technique described later. Seventeen of these patients completed at least 10 months of CT or angiographic follow-up, and they constituted the study group.

Fig. 1F.

35-year-old man with intrarenal bleeding in large angiomyolipoma of left kidney. Contrast-enhanced axial CT scan shows large (largest diameter, 13 cm) angiomyolipoma (arrows) before embolization.

Fig. 1G.

35-year-old man with intrarenal bleeding in large angiomyolipoma of left kidney. Unenhanced axial CT scan at same level as F after three embolizations shows reduction in tumor size (arrows) and coil artifacts 41 months after first embolization.

The subjects were 13 women and four men 24-82 years old (mean age, 55 years). Twelve (71%) of the patients (eight women and four men; age range, 35-82 years; mean age, 61 years) had the sporadic form of AML. Five (29%) of the patients (all women; age range, 24-59 years; mean age, 41 years) had the TS form. One of these patients also had pulmonary lymphangiomatosis. The 17 patients had 18 AML tumors. In one patient with TS, two tumors were found in the same kidney. Symptoms were present in 13 patients and included retroperitoneal hemorrhage (n = 8), hematuria, (n = 1), and flank pain (n = 4). The other four patients had no symptoms, and the tumors were incidental findings. All five patients with TS presented with retroperitoneal bleeding. Only three of the eight patients with retroperitoneal bleeding were treated during the acute bleeding phase. They were inpatients at our hospital. The other five patients were treated on an ambulatory basis several weeks to months after the hemorrhagic episode. These patients were referred from other institutions after they had been given supportive treatment and the diagnosis had been made.

In all patients, the diagnosis was made with unenhanced and enhanced CT on the basis of the presence of lipomatous components in the tumor [1, 16]. Tumor size ranged from 5.5 to 20 cm (mean, 10 cm) measured in the largest of the x-, y-, or z-axis diameter on CT scans obtained before angiography. Tumor size was 5-18 cm (mean, 11.7 cm) in the group with the TS type of AML and 5.5-20 cm (mean, 9.3) in the group with the sporadic type.

Embolization Technique

Two interventional radiologists performed all procedures. One of them participated in all procedures. Transarterial catheter embolization was performed through the common femoral artery with 5-French angiographic catheters. All diagnostic digital subtraction angiographic examinations started with a flush aortogram for evaluation of extrarenal arterial feeders to the tumor. After aortography, selective renal artery catheterization was performed. After careful review of the arteries feeding the tumor, small coaxial catheters (2.5 French, Tracker, Boston Scientific, or 2.7 French, Leggiero, Terumo) were used for selective catheterization of each feeding artery as far distally as possible to prevent arterial spasm and reflux of the embolization material to normal parenchymal arteries. With this superselective injection, arteriovenous shunting and the amount of embolization mixture were evaluated. Embolization was performed with a mixture containing 20 mL of absolute ethanol and 1 mL (1 bottle) of 45- to 150-µm (Contour, Target) or 47- to 90-µm (Cook) PVA particles. To prevent dilution of the ethanol, no opacifying agent was added. Balloon occlusion was not used.

The embolization mixture was carefully injected with a 1-mL syringe in 0.3- to 0.5-mL doses, which were gently pushed with 1 mL of contrast material for verification of arterial occlusion. When embolization neared the occlusion point, the radiologist obtained a selective control angiogram. If reflux to normal arteries was seen, the radiologist considered, according to his experience, whether to continue or to stop embolizing the vessel. Once complete occlusion of one feeder artery was achieved, another feeding branch was catheterized, investigated for shunting and amount of contrast material, and embolized in the same manner as the first until all arterial feeders were occluded. An effort was made to achieve complete tumor devascularization. Control renal or segmental angiograms were obtained during the procedure for evaluation of changes in tumor vascularity during the embolization procedure, especially to find extrarenal feeder vessels and arteriovenous shunts. Control renal angiography was performed at the end of each procedure.

Minicoils with a diameter range of 2-5 mm (Tracker, Boston Scientific) were used in two situations, either to occlude single aneurysm feeders (two aneurysms in one patient [Fig. 1C]), or in follow-up embolizations, to occlude hypertrophic capsular arterial feeders that had been of normal size on the previous angiogram and only after the ethanol-PVA mixture was used and stasis achieved.

The mean embolization procedure time was 70 minutes (range, 45-160 minutes). Conscious sedation with midazolam and meperidine was administered on an individual basis according to the decision of the radiologist in charge. Antibiotic prophylaxis was not given.

After groin hemostasis was achieved, patients were transferred to the urology department for an overnight stay and were usually discharged the day after the procedure. Patients with postembolization syndrome were given supportive treatment until symptoms resolved.


The patients underwent outpatient follow-up examinations by the urology team 3-6 months after the procedure and once a year thereafter. Follow-up CT was performed 10-66 months (mean, 23 months) after the procedure on all patients, including the patients who were later lost to follow-up. Conventional unenhanced and enhanced axial scans were obtained at different institutions with different equipment and protocols. The interventional radiologists reviewed for tumor size the CT scans obtained before the procedure as well as the follow-up CT scans.

Fig. 2A.

44-year-old woman with bleeding angiomyolipoma of upper pole of left kidney. Anteroposterior digital subtraction angiogram obtained before embolization shows moderate tumor vascularity (arrows).

Fig. 2B.

44-year-old woman with bleeding angiomyolipoma of upper pole of left kidney. Follow-up anteroposterior angiogram 16 months after embolization shows obliteration of angiogenic component.

Fig. 2C.

44-year-old woman with bleeding angiomyolipoma of upper pole of left kidney. Contrast-enhanced axial CT scan in acute bleeding phase shows tumor (arrows) with maximum diameter of 12 cm.

Fig. 2D.

44-year-old woman with bleeding angiomyolipoma of upper pole of left kidney. Contrast-enhanced axial CT scan 37 months after embolization shows mainly lipomatous well-defined tumor (arrows). Maximum diameter decreased to 6.5 cm.

Follow-up angiograms were obtained for evaluation of the durability of embolization and for embolization of recurrent angiogenic components. This follow-up angiographic examination was part of a continuous treatment strategy to show that planned-interval embolization is successful in obliteration of the angiogenic component and prevention of bleeding and rupture. The end point of this treatment strategy was obliteration of the vascular component as seen on digital subtraction angiograms 12 months after the last embolization.

Fig. 3A.

24-year-old woman with tuberous sclerosis who had undergone right nephrectomy because of uncontrolled bleeding angiomyolipoma. Preventive embolization of angiomyolipoma in left kidney was performed. Angiogram before embolization.

Fig. 3B.

24-year-old woman with tuberous sclerosis who had undergone right nephrectomy because of uncontrolled bleeding angiomyolipoma. Preventive embolization of angiomyolipoma in left kidney was performed. Angiogram after embolization.

Fig. 3C.

24-year-old woman with tuberous sclerosis who had undergone right nephrectomy because of uncontrolled bleeding angiomyolipoma. Preventive embolization of angiomyolipoma in left kidney was performed. Follow-up angiogram 60 months after first embolization shows hypertrophic capsular artery (arrow) supplying angiomyolipoma. Lesion was embolized with ethanol-polyvinyl alcohol mixture and minicoil.

Fig. 3D.

24-year-old woman with tuberous sclerosis who had undergone right nephrectomy because of uncontrolled bleeding angiomyolipoma. Preventive embolization of angiomyolipoma in left kidney was performed. Angiogram after second embolization.

Fourteen patients with 15 tumors underwent one follow-up angiographic examination 9-60 months (mean, 12 months) after the first embolization and after clinical evaluation. Four patients underwent a second follow-up angiographic examination 22-29 months (mean, 27 months) after the first embolization.

One TS patient with bilateral tumors underwent embolization of the left kidney and 9 months later underwent embolization of the right kidney. At the second embolization, follow-up digital subtraction angiography was performed on the left kidney. The patient was lost to further follow-up, so there was follow-up on one kidney only. The patient later was found to have died of gastric carcinoma 5 years after embolization.


Aortography revealed only one extrarenal feeder from a right intercostal artery in a huge right renal tumor (20 x 18 x 12 cm). Angiography showed the tumors had the characteristic features of AML [17]: large tortuous vessels with aneurysm formation of different sizes (largest, 4 cm) (Figs. 1A, 1B, 1C, 2A, and 3A). These vessels were easily differentiated from the normal renal vasculature. No arteriovenous shunting was found in any tumor. Vascular fragility was seen in four cases: During manipulation of the coaxial catheter, rupture of small vessels occurred with stable contrast extravasation without pain or signs of acute hemorrhage. The amount of ethanol used was 0.5-35 mL (mean, 7.5 mL per procedure). Five minicoils (one 5 mm/3 cm and four 3 mm/3 cm) were used in two tumors for embolization of aneurysm feeder vessels. Complete immediate devascularization of the angiogenic components was achieved in 17 tumors, a 94.4% technical success rate. The one technical failure was incomplete tumor embolization due to the presence of a small difficult-to-catheterize, tortuous arterial feeder. The patient later underwent two successful embolization procedures 22 months apart (the second procedure was performed 9 months after the first and the third procedure, 13 months after the second), and reduction of the tumor size and the angiogenic component was achieved.

Follow-up CT scans obtained 10-66 months (mean, 22.4 months) after treatment were available for all 17 patients. No tumor had grown; two had not changed in size; and 16 were smaller. The largest diameter of the tumors had decreased to 1.5-8 cm (mean, 7.6 cm; mean reduction, 24%) (Figs. 1F, 1G, 2C, and 2D). In the TS group, follow-up CT was performed a mean of 24.7 months (range, 10-66 months) after treatment, and tumor size was 1.5-18 cm (mean, 9.2 cm; mean reduction, 21.4%). In the sporadic group, follow-up CT was performed a mean of 21.3 months (range, 10-41 months) after treatment, and tumor size was 2.8-13 cm (mean, 6.9 cm; mean reduction, 25.8%).

Fourteen patients with 15 tumors underwent their first angiographic follow-up examination 9-60 months (mean, 14 months) after treatment. No new or recurrent angiogenic component was seen in four patients (Figs. 2A and 2B), one of them with TS. These patients thus had reached the treatment end point. In 11 tumors (five TS type, six sporadic type), the vascular component was smaller than before the first embolization, and embolization was repeated (Fig. 1D). In three of these patients a hypertrophied renal capsular artery supplying the tumor was found. These capsular arteries were embolized with the ethanol-PVA mixture, and after complete stasis was achieved, one 2 mm/3 cm minicoil was placed to prevent recurrence in each of these vessels (Figs. 3A, 3B, 3C, and 3D).

Four patients underwent a second angiographic follow-up examination 22-29 months (mean, 27 months) after treatment. One of these patients had TS; two had large masses occupying most of the kidney (Figs. 1A, 1B, and 1F), and one had evidence of partial failure of the first embolization. In the patient with TS, no recurrence of the angiogenic component was seen, so she had reached the treatment end point. In the other three patients, vascularity was reduced, and embolization was repeated (Fig. 1E). Follow-up angiography and embolization were performed in the same manner as the first procedures with the ethanol-PVA mixture and minicoils as deemed necessary.

Five patients (two with TS), who had five (33.3%) of the tumors, arrived at the treatment goal, which was absence of angiogenic components at digital subtraction angiography, 12 months after the last embolization. In 10 (66.6%) of the tumors, the angiogenic component had become smaller, and further digital subtraction angiography was planned. Three patients did not undergo follow-up angiography. One patient, who had no symptoms, refused further intervention. The other two (one with bleeding in the renal sinus and one with pain) did not undergo further treatment because of advanced age and poor general health and after a thorough discussion with the urologist. All three of these patients underwent follow-up CT.

No complications occurred during or after the procedures, and there was no rupture of a tumor or retroperitoneal hemorrhage after embolization or during the follow-up period. No nontargeted embolization was documented. One tumor had liquefied 1 month after embolization. The patient had no symptoms, so intervention was not needed. Two patients had postembolization syndrome of nausea, low-grade fever, headache, and flank pain on the treated side. These patients were treated with IV fluids and nonsteroidal antiinflammatory medication until symptoms subsided, and they were discharged from the hospital after 3 and 4 days. All other patients were discharged 24 hours after the procedure. Of the four patients with flank pain, in three, the pain resolved during the first year of clinical follow-up. In one patient, the pain did not resolve despite successful embolization.


Treatment of patients with symptomatic renal AML is definitely indicated, but there is debate regarding the size criteria for treatment of patients with asymptomatic AML. Most published data indicate that asymptomatic tumors larger than 8 cm should be treated because of high bleeding risk [1, 2, 5, 6, 8, 18]. Some clinicians favor treatment even for asymptomatic tumors when they are larger than 4 cm [5, 8, 14]. At our institution, we offer embolization to every patient with an asymptomatic tumor larger than 4 cm and to all patients with symptomatic tumors [4, 5, 9].

With conventional unenhanced and enhanced CT in the follow-up period after embolization, we found only 24% mean reduction in tumor size, as have other investigators [4, 11, 12]. We did not wait for clinical recurrence. We performed the first diagnostic angiographic examination a mean of 14 months and a second examination a mean of 27 months after embolization to evaluate the remains of the angiogenic component and to look for regrowth, which is the source of renewed bleeding in these tumors [5-7]. Embolization was repeated when growth of new vessels was seen. That reduction or obliteration of the angiogenic component occurred even without marked change in tumor size showed that size should not be considered a risk factor for bleeding after embolization and that surgical removal is not necessary (as it would be with the size criterion).

Transarterial catheter embolization of renal AML is a documented treatment option [3, 4, 6, 10, 12-14]. Most investigators use absolute ethanol as the main embolization material, with or without iodized oil [4, 12, 13, 14, 19] because it is easily administered, diffuses through the entire tumor vasculature, permanently occludes the arteries at the capillary level, and causes tumor infarction and necrosis [7, 15]. Han et al. [13], Lee et al. [12], and Kothary et al. [14] reported their experience with a mixture of ethanol and iodized oil in relatively large patient series. Han et al. treated five patients with this mixture and another nine patients with different embolic material. After imaging follow-up examinations at least 12 months after embolization, the 14 patients had a mean reduction in tumor size of 70.2%, and no vascularity seen on CT or sonography. The investigators did not perform digital subtraction angiography to evaluate the angiogenic components, and they did not report separately on follow-up of the patients who underwent ethanol and iodized-oil embolization. Lee et al. treated 15 patients with 21 tumors, all with a mixture of ethanol and iodized-oil. The mean follow-up period was 35.6 months. These investigators reported decreased size in 12 tumors and no change in eight. Two of the patients had bleeding during the follow-up period. Lee et al. also did not perform follow-up digital subtraction angiography. Kothary et al. treated 19 patients with 30 tumors with a mixture of ethanol and iodized-oil. The mean follow-up period was 51.5 months. The recurrence rate was 42.9% with recurrence only in the TS group of nine tumors. Recurrence manifested as tumor growth, pain, and bleeding. The authors treated the recurrence by the same method of embolization as the first procedure.

We used an approach different from that of the foregoing investigators. First, we added the smallest PVA particles available (45-150 µm) to ethanol, surmising that the particles would augment the effect of ethanol on the vascular bed by producing stasis in the small arteriolar bed and prolonging the effect on the arterioles. This mixture may not directly affect the tumor capillary bed, but it has the advantage of being a combination of two permanently occlusive materials, each of which may augment the influence of the other. Because no intratumoral arteriovenous shunting was seen, it was deemed safe to use small particles without allowing embolization through the lesions to nontargeted areas. We used coaxial systems and superselective catheterization of all tumor feeders, as did Lee et al. [12] in most of their cases. We also embolized the feeding vessels with a very small amount of ethanol-PVA mixture in each injection (0.3-0.5 mL) to avoid reflux to normal renal parenchyma. By using this technique we did not find it necessary to opacify the ethanol-PVA mixture as other investigators have [4, 12, 14, 19], allowing us to introduce more ethanol to a given vessel. Other authors have used occlusion balloons with ethanol embolization [4, 7, 12, 13, 14], but these balloons can be used only in fairly large feeders, and not as precisely as with the coaxial technique.

Second, we made an effort to perform follow-up digital subtraction angiography 1 year after embolization to evaluate and, if needed, to repeat embolization of the angiogenic component of the tumor. We assumed that if no vascularity was seen after 1 year, the possibility of future bleeding was very low, an assumption proved with continuous follow-up.

In this series, our treatment goal of complete obliteration of the angiogenic component was met in five (33.3%) of 15 tumors. The vascular component was reduced in 10 (66.6%) of the tumors, and follow-up was continued for these patients. These results suggest that embolization with the ethanol-PVA mixture has a durable midterm effect. It is significant that we did not see retroperitoneal hemorrhage or tumor growth in any of the treated patients during the 8 years of the study, which is a better result than that reported by others [12, 14].

Four patients were treated for flank pain. This symptom is not specific and was not the indication for treatment but only for further investigation with CT, which showed tumors of the size that is an indication for treatment. Nevertheless, in three patients the pain resolved during the first year after embolization, which may suggest the AML was the cause of the pain. One patient continued to have abdominal pain of unknown cause after successful embolization.

The most important limitation of our study was the small series of patients with relatively short follow-up, which made statistical analysis impossible. The small size of the study group was due to the rarity of the lesions; unless a worldwide registry is formed, this limitation will not be solved. For the same reason, it was impossible to conduct a comparative prospective study, the results of which may have been statistically significant. The follow-up period in this study, although fairly long, must be lengthened to obtain further confirmation of the results. Another limitation was that we did not use CT angiography protocols for all patients, and the findings may have been predictive of the angiogenic component of the tumors. Most of the follow-up CT scans were obtained at institutions other than ours with CT equipment different from ours, and we did not have control over the protocols. That is why we used CT to evaluate the size and general structure of the tumors and not for evaluation of the angiogenic component. Fast acquisition helical CT and power Doppler sonography may obviate the use of angiography as the follow-up technique. This issue can be addressed in future studies comparing CT angiography and conventional angiography in the evaluation of renal AML.

In conclusion, on the basis of these results we favor embolization with an ethanol-PVA mixture as the primary treatment to obliterate or reduce the angiogenic component of renal AML, minimizing the risk of bleeding, even without reduction in tumor size. Tumors with a rich angiogenic component should be managed with several embolization procedures.


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Autor: Uri Rimon, Mordechai Duvdevani, Alexander Garniek, Gil Golan, Paul Bensaid, Jacob Ramon and Benyamina Morag

Fuente: American Journal of Roentgenology. 2006; 187:762-768

Ultima actualizacion: 1 DE AGOSTO DE 2007

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