Clinical Efficacy of Super-Selective Renal Artery Embolization for Rupture of Renal Angiomyolipoma ================================================================================================== * Xu-hua DUAN * Guo-feng ZHOU * Gan-sheng FENG * Chuan-sheng ZHENG * Hui-min LIANG * Song-lin SONG ## Abstract **OBJECTIVE** To evaluate the efficacy of selective transcatheter arterial embolization (TAE) in renal angiomyolipoma (AML) spontaneous ruptures with hemorrhage. **METHODS** A retrospective evaluation was carried out in 21 renal AML cases with acute bleeding confirmed by imaging. Selective renal arterial embolization was used to control bleeding. All the cases were detected by renal arteriography had abnormal vascular hyperplasia and enlarged blood vessels. **RESULTS** Initial renal arteriography for all the patients showed that tortuous, hypervascular, and aneurysm-forming angiogenic components with aneurysm formation occurred in 13 cases (61.9%) and extravasation of the contrast agent was found in 8 cases (38.1%). Immediate complete obliteration was technically successful in 19 (90.5%) of the 21 patients. To prevent uncontrollable complications, 3 patients received nephron-sparing surgery after hemodynamic status was stabilized with TAE a week later. Two days and 3 days after the embolizations, 2 patients presented with incomplete embolizations and then underwent nephrectomy when they were in a stable condition. There were no significant differences in the plasma creatinine levels before and after the treatment. All the patients were followed up for 6 months to 6 years (median, 45 months). The largest tumor diameter was reduced from (11.57±4.28) cm to (9.57±2.28) cm. The tumor had no blood supply and no relapses have occurred. **CONCLUSION** TAE is a technically feasible and minimally invasive procedure for ruptured renal angiomyolipoma. The aneurysms were a predictor of renal AML spontaneous rupture and detection of such aneurysms by CT may help to determine the timing of embolization. In patients who still need surgical treatment, TAE can make tumor resection easier to perform and reduce blood loss during the operation. KEY WORDS: * renal angiomyolipoma * hemorrhage * artery embolization * therapy ## Introduction Renal angiomyolipoma (AML) is a benign hamartomatous tumor that contains adipose tissue, smooth muscle, and vascular tissue[1]. Renal AML has no clear boundaries, and the blood vessels in the tumor differ in size, and present with unusual tortuosity. Some small vessels which have insufficient elastic layer and muscle wall, leading to the formation of aneurysms, are prone to rupture, resulting in hemorrhage[2]. This spontaneous rupture may cause life-threatening hypovolemic shock, which requires nephrectomy or nephron-sparing surgery. Technical improvements in transcatheter arterial embolization (TAE) and increased skill in its use have led to it being widely used to treat acute hemorrhage caused by ruptured renal AML. This study selected 21 patients who were diagnosed as renal AML and underwent emergency super-selective renal artery embolization in our hospital from February 2003 to September 2009. In the study, a mixture of polyvinyl alcohol (PVA) particles and coils of multiple sizes were used to embolize the spontaneous ruptures of the renal AML in order to stop the hemorrhage. The present study describes the effects and patient outcomes after application of arterial embolotherapy. ## Materials and Methods ### Materials The subjects included 15 female and 6 male patients aged 31–59 years (mean 48 years). One (4.8%) patient was diagnosed as having a tuberous sclerosis complex based on criteria that included specifc clinical features determined during a 1998 consensus conference[3]. Renal AML are recognized as hamartomatous lesions composed of heterogeneous tissue components including blood vessels, smooth muscles, and fat. An unenhanced abdominal CT image revealed that the kidney had lost its normal morphological structure. CT imaging showed that the density of the internal structure of the renal AML was heterogeneous, including multiple low-density (fatty tissue) areas. Intratumoral hemorrhage of the renal AML presented as a sheet or map-like high-density area. Renal subcapsular hemorrhage demonstrated crescentic or sickle-shaped high density around the kidney edge. Perirenal hematoma presented strip-like high density around the kidney and the perirenal fat area presented higher density. Retroperitoneal hemorrhage was shown as inhomogeneous fluid density in the perirenal space and around large blood vessels. An enhanced CT scan showed augmented images of some parts of the tumor; the high-density area visible in the unenhanced CT image did not show significant enhancement on the enhanced CT image. The diagnosis of rupture was based on findings of the CT scan[4–6], on the symptoms, such as abdominal or back pain, and on the laboratory findings, such as a 30% decrease in hematocrit. ### Methods Endovascular treatment was applied immediately or 1 day after the rupture for the patients with hemorrhagic renal angiomyolipoma. The endovascular treatment plan used was based on the proposals of the urologists and interventional radiologists in the hospital. Abdominal aortography was performed to locate bilateral renal arteries and to obtain the number and morphology of the renal arteries. Then selective renal angiography was performed to determine the number and size of the arteries that supplied blood to the tumor and to find out whether the accessory renal arteries, lumbar artery or other arteries supplied the blood to the renal AML. Selective embolization of the renal AML was achieved using a 5F catheter to access the main renal artery, and then super-selective catheterization into the vessels of the tumor was performed using a 2.7 F coaxial catheter system (Terumo, Tokyo, Japan) in order to spare as much renal parenchyma as possible. By observing the aneurysm and the number of tumor blood vessels, ethanol and/or PVA particles (Cook, Bloomington, IN, USA) were carefully injected into the selected vessels of the tumor to embolize the distal small branches of the bleeding arteries through the catheter. For patients with aneurysms, PVA was used to embolize bleeding arteries and the feeding vessels of the aneurysms, and then coils were used to embolize the proximal artery trunk which supplied the blood to the aneurysms. Patients with a large tumor, rich in angiogenic component, and without aneurysms underwent embolization using PVA and ethanol. Contrast medium was injected through the catheter to detect the progress of the embolization at intervals. Coils were used to embolize the main feeding arteries supplying the blood to the tumor. Complete embolization was defned as complete obliteration of tumor vessels and lack of opacifcation of the tumor itself according to post-TAE images. After groin hemostasis was achieved, patients were transferred to the interventional ward and their vital signs, urine color, and urine output were observed. Patients with postembolization syndrome were given supportive and anti-infective treatments until the symptoms disappeared. The routine tests for blood, urine, and renal function were conducted within 5–7 days after TAE. As a preoperative adjuvant treatment to reduce blood loss during surgery[7,8], TAE can be used for prophylaxis of high-risk tumors, for acute management of tumor bleeding. After emergency TAE, which was minimally invasive, the patients who were unsuitable candidates for surgery owing to their hemodynamic instability and medical comorbidities were able to undergo further surgery, such as nephrectomy or nephron-sparing surgery. Operating procedures were planned based on proposals raised by the hospital urologists and interventional radiologists. The indications for surgery included the need to decrease the risk of developing complications induced by retained blood clots and by necrotic tumors in the retroperitoneal space, and the need to obtain biopsy specimens for pathological diagnosis. Follow-up CT was performed 6 months after TAE and repeated at intervals in the following 72 months for all the patients, including those patients who were later lost to follow-up. Enhanced CT was carried out systematically every 6 months or yearly after the embolization to assess the changes in aneurysms, tumor enhancement, and tumor volume. ## Results In this study, all cases were diagnosed as renal AML leading to spontaneous rupture based on the CT examination. The mean size of the renal AML was (11.57 ± 4.28) cm (range 7.3–15.9 cm) measured in the largest of the x-, y-, or z-axis diameter on CT scans before TAE was performed. Aneurysms were visible on contrast-enhanced CT images of 9 (42.9%) patients (Figs.1,2). ![Fig. 1.](http://www.cancerbiomed.org/https://www.cancerbiomed.org/content/cbm/8/3/163/F1.medium.gif) [Fig. 1.](http://www.cancerbiomed.org/content/8/3/163/F1) Fig. 1. A 72-year-old woman with a single kidney had a right renal angiomyolipoma (AML), accompanied by acute fank pain and hematuria. (A) CT showed a renal AML in the right renal lower regions with a capsule-like pseudoaneurysm (long arrow). (B) Superselective angiography showed a right renal tumor with multiple tumor vessels (short arrows) and pseudoaneurysm (long arrow). (C) Right renal angiography after embolization showed complete occlusion of all tumor vessels, no obvious tumor staining, and signs of contrast medium overflow. (D). Follow-up CT showed tumor shrinkage from 6.5 cm × 12 cm to 5.1 cm × 7.6 cm with no remaining pseudoaneurysm after 14 months. ![Fig. 2.](http://www.cancerbiomed.org/https://www.cancerbiomed.org/content/cbm/8/3/163/F2.medium.gif) [Fig. 2.](http://www.cancerbiomed.org/content/8/3/163/F2) Fig. 2. A 60-year-old woman had a right renal angiomyolipoma (AML), accompanied by hematuria and shock. (A) Abdominal enhanced CT demonstrated a large renal AML, largest diameter 15 cm, with fat content over the anterolateral area of the right kidney. A mixed low-density area, including adipose tissue, smooth muscle, and vascular tissue, was surrounded by high-density hemorrhage (arrowheads). An aneurysm, with largest diameter 0.8 cm, can be seen in the renal AML (long arrow). (B) The arterial nephrographic phase revealed tortuous and spiral vessels in the hilar region (long arrow) due to a tumor, with abnormal pooling of contrast at the end of a tumor vessel (short arrow), corresponding to the aneurysm in (A). (C) The lesion was embolized with polyvinyl alcohol and coils. Angiography after embolization showed complete devascularization of the tumor. Renal angiography showed the renal artery and its branches; no thicker, abnormal tumor vessels or multiple aneurysm formation in the tumor were found. In the tumor, blood flow was seen to be slow, and there was a clear delineation between tumor blood vessels and normal blood vessels in the renal tissue. An onion-skin-like appearance was shown in the venous phase. During angiography, aneurysms were seen in 13 (61.9%) cases (Figs 1–4), aneurysm rupture in 1 case (4.8%) (Fig.3) and extravasation of contrast in 8 (38.1%) cases (Figs. 1, 3, 4). Evident arteriovenous fistulas were undetected. The size of the largest aneurysm was measured on the angiographic images and the mean size found to be (2.57 ± 1.12) cm (range 0.6–3.6 cm). ![Fig. 3.](http://www.cancerbiomed.org/https://www.cancerbiomed.org/content/cbm/8/3/163/F3.medium.gif) [Fig. 3.](http://www.cancerbiomed.org/content/8/3/163/F3) Fig. 3. A 36-year-old man with a right renal angiomyolipoma (AML) with high adipose component, presented with fever, hematuria, and right flank pain. (A) Right renal angiography showed a spherical-like renal AML in the right renal lower regions. The arterial nephrographic phase revealed a capsule-like pseudoaneurysm which had complete, smooth edges, with largest diameter 3.5 cm. (B) During manipulation of the catheter, renal angiography showed aneurysm rupture with pooling of contrast at the bottom of the aneurysm. (C) An angiogram showed superselective catheterization of the aneurysm feeder. Postembolization arteriography found no aneurysm imaging after coil embolization performed with renal artery trunk spasm owing to improper operation. ![Fig. 4.](http://www.cancerbiomed.org/https://www.cancerbiomed.org/content/cbm/8/3/163/F4.medium.gif) [Fig. 4.](http://www.cancerbiomed.org/content/8/3/163/F4) Fig. 4. A 38-year-old woman had a left renal angiomyolipoma (AML) with acute abdominal pain, nausea, vomiting, and incoagulable blood drawn by abdominal paracentesis. (A) Angiography showed abundant, messy and tortuous vessels supplying the tumor, which had several aneurysms of different diameters. There was no clear delineation between tumor and normal tissue. (B) Upper renal regions revealed renal AML, with largest diameter 14 cm, and delayed emptying of contrast agent in the aneurysms. (C). After embolization left renal angiography showed occlusion of most tumor vessels of the right AML and no extravasation of the contrast agent. TAE was performed once for all the patients. In the 13 patients with aneurysms, 9 underwent embolization using PVA and coils or minicoils of different sizes (Fig.1). After embolization, angiography of the 9 cases showed occlusion of all the vessels in the tumor and in the aneurysms. For the other 4 patients, after embolization using PVA and ethanol, angiography showed occlusion of most vessels in the renal AML but not for the vessels in the aneurysms. Target arteries were successfully embolized with coils, and no remaining aneurysms were found during the follow-up angiography check-up (Fig.4). Nine coils and 5 minicoils were used in these 13 cases. Eight patients underwent embolization using PVA and ethanol. The amount of ethanol used for each procedure was 3–15 mL (mean 6.5 mL). Three of the 21 patients had bilateral renal AML, and they received nephron-sparing surgery for the bleeding kidney a week after the successful embolization. In the 4 patients for whom PVA, ethanol and coils were used in the embolization, 2 of them had nephrectomy after the embolization, 1 had hematuria and 1 was still bleeding, confirming incomplete embolization in these last 2 cases. In one case (Fig.3), TAE was incomplete owing to a spasm occurring because of tortuous arterial supply. Three days after the embolization, this patient continued to have hematuria, but it was effectively controlled, as was the back pain of this patient. Symptoms of shock faded after TAE, and after resection of the dysplastic kidney, hematuria disappeared in this patient. In another case (Fig.4), the day after the embolization, the patient suddenly presented tachycardia, decreased blood pressure, abdominal distension but without increased tension. Ultrasound showed a large amount of ascites in the abdomen of the patient. A tube was inserted into the peritoneal cavity and 1000 mL of incoagulable bloody ascites was drained. Fifteen days after the emergency nephrectomy, the patient was discharged. For the 2 patients with renal AML with a tumor diameter > 10 cm, fewer normal renal units remaining, and more blood clots and necrotic tumor tissues, re-embolization was less clinically effective. These 2 patients underwent nephrectomy 1 week after TAE. In this study, all patients survived after receiving TAE. Technically successful outcomes which achieved an immediate complete obliteration of the tumour occurred in 19 (90.5%) of the patients. The frequency of recurrent bleeding was 9.5% after the 1st TAE. The surgery rate among the patients was 23.8%, including 14.3% who underwent nephron-sparing surgery and 9.5% nephrectomy. The demographic and clinical characteristics of the patients in this study and the syndrome they developed after embolization are shown in Table 1. After embolization, 3 patients’ blood pressure rose as the shock symptoms were removed. Hematuria occurring in 8 cases disappeared after 24 h. The body temperature of 3 patients returned to normal after 3 days. None of the patients had significant changes in creatinine level before or after embolization. All patients had postembolization syndrome, presenting with fank pain (*n* = 19), fever (*n* = 10) or vomiting (*n* = 5), which were easily managed with conservative treatment, and within 1 week, the patients had recovered. View this table: [Table 1.](http://www.cancerbiomed.org/content/8/3/163/T1) Table 1. Demographics and clinical characteristics of patients. After embolization, none of the patients had further ruptures of the tumor or retroperitoneal hemorrhage during the follow-up. The patient whose left kidney was removed was lost to the follow-up 6 months after TAE. The remaining patients were followed up for 9 months to 6 years. The tumor size was observed during the follow-up, using CT in 15 cases and CT together with US in 5. The mean size of the renal AML was reduced to (9.57 ± 2.28) cm (range 7.3–11.9 cm). Images of the kidney of the 3 patients undergoing nephron-sparing surgery were normal. ## Discussion Renal AML grows slowly and patients’ clinical symptoms are associated with tumor size and tumor location. Therefore, patients with smaller renal AML have no apparent clinical symptoms. As a renal AML enlarges, it usually becomes more vascular, and then develops tortuous vessels and aneurysms that are prone to rupture[9]. The most serious complication of renal AML is spontaneous rupture of the tumor. Patients may have sudden low back pain due to bleeding of the renal AML tumor vessels, resulting in dramatically increased tumor volume. When the tumor growth reaches the renal capsule, the patients may have an acute abdomen or hemorrhagic shock caused by retroperitoneal hemorrhage arising from the tumor bleeding. As renal AML is a benign tumor, radical nephrectomy and nephron-sparing surgery have been the traditionally used treatments. Currently, TAE has become increasingly popular in the management of renal AML, sparing the normal renal parenchyma, managing acute tumor bleeding, and being used as a preoperative adjuvant treatment to reduce blood loss during surgery[7, 8,10]. For patients with multiple renal AML, undergoing the high risk of surgery or with acute bleeding, embolization should be actively applied[11]. The tendency for bleeding originates from the irregular, tortuous, aneurysmal blood vessels that constitute the angiogenic component of the tumor[12]. The larger the tumor size, the greater the risk of bleeding[13]. Nelson[7] and Dickinson[14] observed that an asymptomatic renal AML > 8 cm had a high risk of bleeding, therefore, they suggested that such a tumor should be treated. In this study, the diameters of all the bleeding renal AML were >8 cm and every patient had different degrees of clinical symptoms before the tumor ruptured. Small renal AML can also cause clinical symptoms or bleeding following trauma. Jou et al.[15] reported that 50%–60% of patients might have a spontaneous hemorrhage when tumors were > 4 cm. Soulen et al.[16] estimated that there was a risk of one episode of bleeding for every 3.4 patient-years in patients with a tumor > 4 cm. TAE causes fewer postoperative complications and as a result, hospitalization is shorter than with nephrectomy or nephron-sparing surgery. Therefore, preventive embolization applied to patients with a tumor size > 4 cm has gained increasing acceptance[16,17]. In this study, we used preventive embolization for asymptomatic patients whose tumor size ranged from 4 to 8 cm to stop tumor growth and to avoid spontaneous bleeding or traumatic intratumoral hemorrhage. The abnormal vessels in the renal AML are usually bent into a spiral-shaped kink or sinusoidal vascular network, and the wall of these abnormal vessels becomes glass-like allowing an aneurysm to form easily[2]. Several authors found that the presence of aneurysms > 5 mm had greater specificity for predicting bleeding than lesion size[6,18]. In our cases, aneurysm formation was detected in 13 (61.9%) patients, and the diameters of the aneurysms were > 5 mm as shown during angiography. Furthermore, when prophylactic embolization was used for one of the patients whose aneurysm was about 2 cm, the aneurysm ruptured during the angiography. Although the number of the patients in this study is too small to allow us to reach a definite conclusion, the findings support our hypothesis that there is a significant relationship between tumor size, aneurysm formation, and spontaneous rupture. The presence of aneurysms appears to be a predictor of spontaneous rupture[6]. The detection rate of aneurysm formation by angiography was higher than that by enhanced CT scan in our patients. Advances in CT diagnostic technology may improve the detection of aneurysm formation in renal AML. As aneurysms may be a predictor of spontaneous rupture, their detection by CT would help to determine the timing of treatment. Therefore, prophylactic embolization should be applied to those cases which showed no bleeding of the aneurysm by renoarteriography, irrespective of the size of the aneurysm diameter. Lenton et al.[19] advocated using a combination of PVA and coils in treating renal AML and revealed that PVA used alone in the embolization might induce acute haemorrhage occurring during or after embolization. In our study, we used PVA combined with coils in the embolization for 13 cases. For patients with aneurysms, we used PVA to embolize the bleeding arteries and feeding vessels of the aneurysms, and then used coils to embolize the proximal artery trunk which fed the aneurysms. PVA 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, and the combination of PVA and ethanol may augment the influence of one on the other[20]. A renal AML with rich angiogenic component but without aneurysms, may benefit from embolization using PVA combined with ethanol; we used this combination in 8 patients with large tumor size and rich angogenic component. This approach is not only less expensive but also increases the outcome of embolization. Further surgical intervention is usually carried out for recurrent bleeding or persistent symptoms[7]. Adhesion forms 72 h after renal AML tissue injury and becomes more intensive at about 10 days to 2 weeks[21]. Jou et al.[15] recommended performing nephron-sparing surgery 1 week after embolization. In our study, the surgery rate (23.8%) was higher than that reported in other studies, probably because our patients had large bleeding renal AML. That owing to ruptured renal AML with considerable bleeding in the 3 patients with bilateral renal AML, the hematoma wrapped around and pushed the kidney. A week after TAE, nephron-sparing surgery was given, reducing the blood loss. Embolization with hemostasis made it possible to halt the hemorrhage and to avoid radical nephrectomy in these 3 patients. During the course of their nephron-sparing surgery, the surgical areas were clear without severe adhesion. In the 2 nephrectomy operations, blod loss was less than that in the nephrectomy operations without TAE, and renal pedicle control was not necessary as the feeding arteries had been obliterated by TAE. Owing to the small number of cases in our study, more data are needed to confirm the safety and efficacy of this method of treating ruptured renal AML. The follow-up CT images of 9 patients and US images of 2 patients were obtained from other hospitals with different equipment than available in our hospital. Accurate measurement of the tumor size at follow-up may be difficult. The small number of the patients and the relatively short follow-up made it difficult to obtain better data for analysis and determine statistical significance. ## Conclusion This study indicates that the aneurysms are a predictor of renal AML spontaneous rupture, and detection of such aneurysms by CT may help to determine the timing of embolization. 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