Efficacy of iodized oil in emergency ultraselective arterial embolization for fatal massive hemorrhage due to renal angiomyolipoma: a single-center retrospective cohort study

Introduction

Background

Renal angiomyolipoma (RAML), a benign tumor of the kidney, is often diagnosed incidentally during physical examination or when the lesion is enlarged and compressed and other symptoms manifest. It typically has a slow-growing, insidious occurrence, originating from the perivascular epithelium. RAMLs, although generally asymptomatic, can cause life-threatening bleeding (1,2). Wunderlich syndrome, an acute nontraumatic spontaneous perirenal hemorrhage, can manifest as large angiomyolipoma (3).

Study rationale

The symptoms of RAML are not specific, and the clinical presentation is of limited value in diagnosing RAML. Ultrasonography, with its excellent accuracy for both computed tomography (CT) and magnetic resonance imaging (MRI), is a screening technique for newly diagnosed patients. Of all the diagnostic methods, CT and MRI have become the most commonly used and essential for diagnosing RAML, which is composed of varying amounts of abnormal neovascularization, immature smooth muscle cells, and adipocytes. If a kidney mass contains fat, RAML is often suspected first. Due to its distinct appearance, CT and MRI or sonography is typically used to diagnose RAML (4).

Rupture of RAML induces macroscopic hematuria or intratumor/retroperitoneal hematoma, destabilizing hemodynamics in turn. For such urgent cases, emergency renal artery embolization is typically performed. In this procedure, the tip of a microcatheter is inserted into an area adjacent as close as possible to the source of hemorrhage (i.e., a ruptured renal aneurysm), and this site is occluded with embolic agent. In many patients, renal dysfunction is present, in which case minimization of embolization-related damage to the peripheral normal renal parenchyma should be prioritized (5). Fat and angiomyogenic components may be significantly reduced after embolization (6).

Objective

We aimed to investigate the efficacy of emergency ultraselective arterial embolization for the treatment of fatal massive bleeding caused by RAML and to clarify the effect of iodized oil in emergency ultraselective arterial embolization in fatal massive hemorrhage due to RAML.

In this study, the onset of RAML and other factors were not considered, for example, whether there has been a combination of other treatment regimens beforehand, only the diagnosis of fatal hemorrhage due to RAML and the treatment of emergency vascular embolization were examined. We present this article in accordance with the STROBE reporting checklist (available at https://tau.amegroups.com/article/view/10.21037/tau-24-473/rc).

Methods

A retrospective study was conducted from January 1, 2019 to March 1, 2024, at The First Hospital of Jilin University. The included patients had severe flank pain, were diagnosed with RAML and hemorrhagic bleeding by CT or MRI in the emergency department, and renal arteriography and vascular ultraselective embolization are performed within 40–60 minutes. Patient information, including age, sex, tumor size, embolic material, several blood laboratory parameters, hospital stay, and postembolization syndrome (PES) occurrence were retrospectively obtained. PES was defined as the presence of fever, pain, nausea, or vomiting.

Throughout the study, two specialists from our department conducted quality control and supervision, which could exclude the influence of operator experience and subjective factors.

Within 5 days after ultraselective embolization treatment, all patients were followed up for changes in blood indexes and postoperative subjective and objective symptoms. Three months after ultraselective embolization, we followed up with patients for further treatment of their choice.

This study was conducted in accordance with the Declaration of Helsinki (as revised in 2013) and approved by the ethics committee of The First Hospital of Jilin University (approval No. 2024-681). The clinical data were analyzed retrospectively and anonymously, and thus the local ethics committee waived the need for informed consent.

With the direction of a digital subtraction angiography (DSA) imaging apparatus, the operator punctured the femoral or radial artery under local anesthesia. An aortogram was obtained first through a 5-F guiding sheath to locate the renal arteries and to identify any accessory renal arteries or extrarenal feeding arteries. Selective renal angiography was conducted to evaluate the vascularization of the RAML, tumor vessel extension beyond the normal nephrogram, vessel displacement by the tumor, and any aneurysms (Figure 1) in patients with severe bleeding, active extravasation, and retroperitoneal blood. Ultraselective catheterization of the RAML feeding vessels was conducted with a microcatheter to ensure maximal sparing of the renal parenchyma (Figure 2). If check angiography identified other feeding vessels, further ultraselective catheterization and embolization were performed (Figure 3). The injection was continued and repeated until the distal end of the feeding arteries of the RAML and their dysplastic portions were completely occluded. The endpoint of the procedure was complete devascularization of the tumor. According to the abnormal vascular structure and shape of renal hamartoma, iodized oil, embolic particles of different diameters, coils, or tissue glue were selected, the embolic agent was injected into the supporting vascular bed of the lesion through the catheter, and all abnormal vascular beds were embolized (Figure 4). Liquid embolic agents allow for complete vascular filling from the proximal trunks to the capillary bed, as well as aneurysms (Figure 5). Postembolization angiography was performed through a 5-F catheter to confirm successful occlusion of the artery and the patency of the branches of other renal arteries. For patients with multiple lesions, the donor arteries could be embolized separately, and for patients with lesions in both kidneys, pathological vascular embolization of both kidneys could be completed at one time. Embolizing the vascular bed of the renal hamartomas was implemented to maximally preserve the normal renal vascular bed. Interventional embolization therapy can achieve treatment, preserve normal kidney tissue, and be conducted in conjunction with surgery so that patients can recover and be discharged from the hospital 5 days after surgery.

Figure 1 Selective imaging of the renal arteries. A left renal giant angiomyolipoma was revealed by imaging, with the two branches of the left renal artery (marked by orange arrows) providing blood to the tumor. Estimated size =9 cm.

Figure 2 Ultraselective cannulation and imaging are performed to confirm the supplying vessel. Ultraselective access to an artery supplying blood to the renal angiomyolipoma as confirmed by angiography, with injection of iodized oil and embolic particle spheres.

Figure 3 Ultraselective hemangioma blood supply branch, complete embolization of the hemangioma was performed after confirmation. Ultraselective access to an artery supplying blood to the angiomyolipoma as confirmed by contrast, with continued injection of iodized oil and embolic particle spheres.

Figure 4 Postembolization imaging review. After ultraselective embolization of the two vessels, angiography was repeated, the staining of angiomyolipoma disappeared (area circled in orange), and the supplying artery was occluded.

Figure 5 Postembolization of iodized oil deposition. Staining of angiomyolipoma is absent (area circled in orange), and iodine oil deposition is good in the previously stained area.

Statistical analysis

Statistical analysis of categorical variables, expressed as frequencies and proportions, and of continuous variables, expressed as the median with interquartile range (IQR) or as the mean with standard deviation (SD), was conducted using SPSS 26 (IBM Corp., Armonk, NY, USA). The Clopper-Pearson method was employed to estimate the 95% confidence interval (CI) of categorical variables.

Results

Three patients were excluded from this study because of irreversible hypovolemic shock at the time of arrival to the emergency department.

Ultimately, 27 patients with severe low back pain who were admitted the emergency department were enrolled in this study. Table 1 details the patients’ clinical characteristics. Upon CT enhancement examination, RAML was identified as being accompanied by perirenal hematoma or hemorrhage, with the formation of aneurysms being observed in some patients. Emergency selective renal angiography was then performed to assess vascularization of RAML, and ultraselective embolization of the vessels supplying RAML was completed to minimize the impact on normal renal arteries.

After emergency ultraselective embolization, the data during patients’ stay at hospital were summarized. After 5 days of observation and monitoring and symptomatic treatment, the changes of the patient’s blood indexes before and after ultraselective embolization were recorded and compared, and the PES of the patients after ultraselective embolization was statistically analyzed.

Red blood cells and hemoglobin stabilized in all patients and began to rise gradually on the third day after ultraselective embolization. Additionally, 27 patients had 100% stable red blood cells and hemoglobin. After emergency ultraselective embolization, 22 patients experienced relief of low back pain compared to pretreatment, and the rate of lower back pain relief was 81.48%. Significantly higher creatinine and urea nitrogen levels were observed in three patients prior to the operation, and these levels reverted to normal following renal function protection therapy. The rate of renal impairment was 11.11%.

The patients had different degrees of PES, but all cases were resolved after symptomatic treatment, and this did not significantly affect the quality of life or recovery period of patients. On the second day after ultraselective embolization, 27 patients began to experience fever, and after anti-infection and symptomatic treatment, their body temperature reverted to normal levels. Severe lumbar pain was completely relieved after ultraselective embolization, and 21 patients had tolerable lumbar pain and lumbar contractures. There were four patients with nausea or vomiting after surgery, who were treated with intramuscular metoclopramide injected and put on a restricted diet, with the symptoms being relieved after intravenous nutrition.

Three months after ultraselective embolization, the patients were followed up in regard to their treatment of choice. Among the patients, seven had a single lesion and underwent surgical resection after the bleeding was stabilized, four patients did not receive follow-up treatment due to personal and medical reasons, and 16 patients continued to be regularly reviewed and monitored. A list of outcomes for all patients is available in Table 2.

Discussion

Key findings

At present, there is no unified standard for the indication of interventional treatment of RAML. However, in the setting of life-threatening bleeding, the consensus is that emergency action and embolism should be initiated. Hemorrhaging caused by RAML can be life-threatening, so it is common practice to treat patients who display symptoms or have tumors greater than 4 cm (7). A previous study found that elective arterial embolization of RAML greater than 4 cm may reduce the risk of hemorrhaging (8). Selective arterial embolization (SAE) has become the preferred management option for RAML in both prophylactic and emergency cases due to the recent technological advances in microcatheters and diagnostic imaging equipment. Now all vascular embolization advocates ultraselection and refinement. In our study, the size of an RAML decreased significantly after ultraselective arterial embolization, but renal function exhibited no obvious change.

In recent years, ultraselective arterial embolization has also become increasingly popular among urologists. In particular, in cases where hemodynamic instability is extremely high due to tumor rupture and hemorrhage, ultraselective arterial embolization has even become the treatment of choice. The recurrence rate in patients who undergone ultraselective arterial embolization is higher than that in patients who undergo excisional surgery and ranges from 30% to 37% in the literature (9,10). However, patients treated with ultraselective arterial embolization have a shorter hospital stay and less blood loss than do those treated with surgery. Common complications include PES, vascular injury, abscess or even renal infarction, and nontargeted vessel embolism. PES involves fever, lower back pain, and leukocytosis and occurs in about 80% of patients but can be resolved with conservative treatment.

Strengths and limitations

The main issue with embolization therapy lies in the balance between the complete occlusion of the blood supply to the RAML and the preservation of the blood supply to normal kidney tissue. At present, the embolic agents mainly used in ultraselective arterial embolization include ethanol, iodized oil, polyvinyl alcohol embolic microspheres, and coils, but there is a lack of comparative data on the safety of these embolic agents in the treatment of RAML.

Comparison with similar studies

In this study, iodized oil and polyvinyl alcohol embolic microspheres were successfully used as primary embolic agents for ultraselective arterial embolization. Iodized oil is a liquid embolizing agent that permanently occludes arteries and capillaries at the distal level of collateral inflow and accelerates necrosis of tumor tissue. The use of iodized oil has not been reported in the literature, and we believe that the use of iodized oil can not only exert an embolic effect but also provide a tracer effect in subsequent reexamination.

Particulate agents, such as polyvinyl alcohol embolic microspheres, are the most common type of embolic materials used for the treatment of RAML and have been classified as permanent embolic agents (11). With a size of 100–300 or 300–500 µm, polyvinyl alcohol embolic microspheres particles facilitate distal vascular occlusion of a tumor. Particulate agents cannot be readily eliminated from target lesions following embolization, which leads to a prolonged delay in the recanalization of tumor-feeding vessels.

Explanation of findings

Typically, we perform embolization using a combination of iodized oil and polyvinyl alcohol embolization microspheres, which block the distal vascular bed of the target lesion. Coils are then used to occlude the arterial inflow and halt the retrograde filling of the aneurysm and the reforming of abnormal tumor vessels (12). The use of coils alone should be avoided, as they only provide proximal blood vessel occlusion, which may lead to the formation of collateral rami around or distal levels of the obstruction and make embolization more difficult or impossible. In our study, 10 patients underwent ultraselective arterial embolization with a combination of iodized oil and 100–300 µm polyvinyl alcohol embolic microspheres, seven patients underwent ultraselective arterial embolization with a combination of iodized oil and 300–500 µm polyvinyl alcohol embolic microspheres, and 10 patients underwent ultraselective arterial embolization with a combination of iodized oil and 300–500 µm polyvinyl alcohol embolic microspheres and coils. There were no obvious differences between the tumor shrinkage rates, and all patients received effective bleeding control after ultraselective embolization.

Limitations

The small sample size and the single-center design of the study may reduce the validity of the results.

Conclusions

Our study demonstrated that ultraselective arterial embolization is a safe and efficient management option for controlling hemorrhage and preventing the progression of RAML. Using iodized oil and polyvinyl alcohol embolic microspheres as embolic agent in ultraselective arterial embolization for RAML can drastically reduce the tumor size and preserve renal function. The use of iodized oil can exert an embolic role while also acting as a tracer for subsequent reexamination.

Further large-scale, prospective studies with extensive follow-up periods will aid in ascertaining the value of ultraselective arterial embolization in the treatment of RAML and in informing the selection of embolic agents.

Acknowledgments

We would like to thank Yang Wang (a medical writer from Suzhou Suncadia Biopharmaceuticals Co., Ltd.) for writing assistance and technical editing.

Funding: This work was supported by the Beijing Dadi Medical Charity Foundation-Efficacy Evaluation Project of Emergency Ultraselective Arterial Embolization in the Treatment of Fatal Hemorrhage Caused by Renal Angiomyolipoma.

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://tau.amegroups.com/article/view/10.21037/tau-24-473/rc

Data Sharing Statement: Available at https://tau.amegroups.com/article/view/10.21037/tau-24-473/dss

Peer Review File: Available at https://tau.amegroups.com/article/view/10.21037/tau-24-473/prf

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tau.amegroups.com/article/view/10.21037/tau-24-473/coif). The authors report that this work was supported by the Beijing Dadi Medical Charity Foundation-Efficacy Evaluation Project of Emergency Ultraselective Arterial Embolization in the Treatment of Fatal Hemorrhage Caused by Renal Angiomyolipoma. The authors have no other conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. This study was conducted in accordance with the Declaration of Helsinki (as revised in 2013) and was approved by The First Hospital of Jilin University (approval No. 2024-681). The clinical data were analyzed retrospectively and anonymously, and thus the local ethics committee waived the need for informed consent.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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(English Language Editor: J. Gray)