Treatment of angiomyolipoma at a tertiary care centre: the decision between surgery and angioembolization.
Abstract: Background:

Angiomyolipoma (AML) is a benign renal neoplasm. First-line therapy includes renal preserving surgery or angioembolization (RAE), both with good outcomes in isolated studies. However, there are no comparative randomized trials and no clinical guidelines to help clinicians decide between these treatment modalities. Our study examines the patterns of AML treatment at a tertiary care centre to evaluate how local urologists have been treating this disease.

Methods:

This is a retrospective study of all AMLs treated at the Vancouver General Hospital (Vancouver, BC, Canada) over the past 10 years with either RAE or surgical excision. Searches were performed of the radiology and pathology dictation systems, using the following keywords: AML, angiomyolipoma, angioembolization, embolization, surgery, partial nephrectomy and nephrectomy.

Results:

At our institution, more AMLs were treated by surgery than angioembolization (42 vs. 17 cases). Angioembolization was more often chosen for cases of multifocal AML (35% vs. 7%) and acute hemorrhage (50% vs. 14%). In the angioembolization cases, particles were the embolic agent of choice (used 40% of the time).

Conclusions:

Angioembolization allows rapid patient stabilization in cases of acute hemorrhage, and provides good renal preservation in cases of multifocal AML. It may also be preferred in large masses when partial nephrectomy is not feasible. Surgery should be performed in cases of diagnostic uncertainty or complex vascular anatomy not amenable to RAE. Prospective randomized studies are needed to compare RAE and surgery to better define their indications in sporadic AML.

Resume

Contexte :

Un angiomyolipome (AML) est une tumeur benigne du rein. Le traitement de premiere intention comprend une chirurgie de conservation renale ou une angioembolisation renale, qui ont toutes deux donne de bons resultats dans des etudes isolees. Cependant, aucun essai comparatif randomise n a ete mene et il n existe pas de lignes directrices pour aider les cliniciens a choisir entre ces modalites therapeutiques. Notre etude a examine les tendances dans le traitement de l AML a un centre de soins tertiaires pour evaluer comment les urologues y traitent cette maladie.

Methodologie :

Il s agit d une etude retrospective de tous les AML traites au Vancouver General Hospital (Vancouver, C.-B., Canada) au cours des 10 dernieres annees, soit par chirurgie de conservation renale ou par angioembolisation. Des recherches ont ete effectuees dans les systemes de dictee vocale de radiologie et de pathologie en utilisant les mots-cles anglais suivants : AML, angiomyolipoma, angioembolization, embolization, surgery, partial nephrectomy et nephrectomy.

Resultats :

Dans notre etablissement, plus de cas d AML ont ete traites par chirurgie que par angioembolisation (42 cas contre 17). L angioembolisation a ete plus souvent choisie dans les cas d AML multifocal (35 % contre 7 %) et d hemorragie aigue (50 % contre 14 %). Dans les cas traites par angioembolisation, les particules ont ete l agent embolique privilegie (utilisees dans 40 % des cas).

Conclusions :

L angioembolisation permet de stabiliser rapidement l etat du patient en cas d hemorragie aigue, et offre une bonne conservation renale en cas d AML multifocale. Elle peut aussi etre preferable en presence de larges masses quand la nephrectomie partielle n est pas possible. La chirurgie doit etre realisee en cas d incertitude diagnostique ou d anatomie vasculaire complexe ne se pretant pas a l angioembolisation renale. Des etudes prospectives randomisees sont necessaires pour comparer l angioembolisation renale et la chirurgie afin de mieux definir leurs indications dans les formes sporadiques d AML.
Article Type: Report
Subject: Connective tissue tumors (Care and treatment)
Connective tissue tumors (Diagnosis)
Connective tissue tumors (Research)
Excision (Surgery) (Health aspects)
Hormone therapy (Health aspects)
Authors: Faddegon, Stephen
So, Alan
Pub Date: 03/01/2011
Publication: Name: Canadian Urological Association Journal (CUAJ) Publisher: Canadian Urological Association Audience: Academic Format: Magazine/Journal Subject: Health Copyright: COPYRIGHT 2011 Canadian Urological Association ISSN: 1911-6470
Issue: Date: March 1, 2011 Source Volume: 5 Source Issue: 4 Pt 1
Topic: Event Code: 310 Science & research Canadian Subject Form: Connective tissue tumours; Connective tissue tumours; Connective tissue tumours
Geographic: Geographic Scope: Canada Geographic Code: 1CANA Canada
Accession Number: 250259964
Full Text: Author(s): Stephen Faddegon, MD, Alan So, MD, FRCSC

Introduction

Angiomyolipoma (AML) is a benign renal neoplasm composed of fat, vascular and smooth muscle elements. The indications for treatment, though somewhat controversial, relate to the inherent risk of spontaneous hemorrhage and include bleeding, pain, large tumour size (often quoted as >4 cm), females of childbearing age and inadequate emergency or follow-up care. Since so many AMLs are small and asymptomatic, over 50% of cases are managed by observation alone.[sup.1]

Fortunately, modern imaging techniques allow for high accuracy of AML diagnosis. Almost all renal masses containing macroscopic fat are AMLs.[sup.2] Fat-containing renal cell carcinomas (RCCs) are so rare, they are only described in case reports. Moreover, all of these lesions contained calcifications,[sup.3]-[sup.7] a finding extremely rare in AMLs.[sup.2] Thus, a renal mass with fat and no calcium is almost certainly AML and, in the absence of other concerning features, can be treated as a benign lesion with angioembolization and simple enucleation. The diagnostic dilemma is the 5% of AMLs that do not contain fat. These lesions are typically identified as RCC and these patients proceed to the appropriate surgical management. Newer imaging techniques, particularly in magnetic resonance imaging, may provide better capability to diagnosis fat-poor AMLs in the future.[sup.2]

The 2 mainstays of treatment for AML are surgery and renal angioembolization (RAE). Other management strategies include surveillance, total nephrectomy and investigational medical management, such as hormonal therapy or use of mammalian target of rapamycin (mTOR) inhibitiors, such as sirolimus.[sup.8] The optimal modality of treatment is still unclear. There are no prospective or randomized studies comparing RAE and surgery, and no treatment guidelines. Instead, urologists must consider several factors including treatment efficacy and morbidity, patient renal function, individual tumour characteristics, operative time and patient/surgeon preference.

As expected, recurrence rates after surgery are extremely rare.[sup.9]-[sup.11] However, in a review of 14 series, RAE required repeat procedures in 14% of cases after a median follow-up of 23 months; these were usually for recurrent symptoms or bleeding.[sup.1] On follow-up imaging after RAE, the decrease in tumour size is variable, but typically averages only 50% to 60%.[sup.12] Although complete eradication is expected after surgery, the risk of bleeding and neoplastic progression remains after RAE, due to the persistence of the disease that is common after treatment.[sup.12]

Renal angioembolization offers the least invasive treatment option. Hospital stay is typically less than 24 hours compared to at least 2 days for surgery.[sup.9] Blood loss associated with RAE is negligible. The most familiar complication is the postembolization syndrome, characterized by symptoms of pain, fever and nausea, reported in up to 85% of cases;[sup.1,13,14] the severity of these symptoms may be proportional to the size of the infarct.[sup.14] Complications from surgery, including hemorrhage, urinary leak/fistula, tend to be more significant but are also rare. Overall, there is a 12% rate of complication for partial nephrectomy, including a 5% risk of urinary fistula.[sup.9]

Unfortunately, there are no randomized studies comparing renal function after partial nephrectomy and RAE, although case series have demonstrated the preservation of renal function with both treatments with median follow-up as long as 8 years.[sup.9,11,12,15,16]

The characteristics of an AML are also likely to influence the decision between surgery and RAE. Some authors suggest that larger AMLs are more often amenable to RAE than partial nephrectomy.[sup.15] Cases presenting with acute hemorrhage are best managed with RAE as it allows more rapid stabilization and avoids total nephrectomy in the emergent scenario.[sup.17,18] Difficult tumour locations (i.e., hilar) can influence the choice of treatment, and in some cases necessitate nephrectomy. Angiomyolipomas can also be mistaken for RCC on imaging, particularly in tumours with low fat content.[sup.19] These suspicious tumours should undergo surgery for definitive diagnosis and management.

Since there are no randomized trials or guidelines to support the use of surgery or embolization, we reviewed our own experience to evaluate how these decisions have been made over the past 10 years.

Methods

This is a retrospective study of all AMLs treated with either RAE or surgery at the Vancouver General Hospital (Vancouver, BC, Canada) over the past 10 years. Subjects were identified by searching the local "Sunset" databases, comprehensive dictation records of all AMLs treated by RAE and all AML-pathology specimens removed surgically.

The Sunset Radiology Intranet Database was searched with the following keywords: AML, angiomyolipoma, TSC (tuberous sclerosis complex), tuberous sclerosis, angioembolization and embolization. The RAE dictated reports were evaluated for patient characteristics, embolic agent used, features of the AML tumour (i.e., size, location) and the treatment indication.

The Sunset Pathology Intranet Database was then searched for following keywords: AML, angiomyolipoma, TSC, tuberous sclerosis, nephrectomy and partial nephrectomy. Pathology reports were evaluated for tumour characteristics, unique pathology (no fat, cystic, epitheliod) and patient characteristics. Patient charts were reviewed for patient characteristics, imaging features (size, location), and the indication for treatment. We excluded all autopsy specimens and patients in whom the AML was not the primary indication for treatment (i.e., patients with coexistant malignancies, trauma nephrectomies).

Results

We report on a total of 59 patients who underwent treatment for AML with RAE or surgery. Both treatment groups displayed the classic over-representation of middle-aged females between 24 and 76 years old. Three patients with multifocal AML underwent multiple RAE procedures to treat different tumours at different times. One RAE patient required a repeat procedure for persistent bleeding. One RAE case was unsuccessful due to the inability to accurately map the tumour because of insufficient vascular aneurysm formation.

Surgical management included 25 (60%) undergoing radical nephrectomy and 17 (40%) undergoing partial nephrectomy. During this time period, all partial procedures were performed through an open procedure, while most complete resections were performed by laparoscopy. No surgical cases required re-operation for any reason. No urinary leakage was reported postoperatively.

At our institution, more AMLs were treated by surgery than RAE (42 vs. 17 cases). Renal angioembolization was more often chosen for cases of multifocal AML (35% vs. 7%) and acute hemorrhage (50% vs. 14%). For RAE cases, particles (most commonly polyvinyl alcohol) were used in 40% of cases, making them the agent of choice, followed by coils (25%), multiple agents (20%) and alcohol (15%) (Table 3).

Within the surgical population, more AMLs were removed via radical nephrectomy than partial nephrectomy (60% vs. 40%). The mean AML size was 5.85 cm (standard deviation 4.4, range 1-15 cm), and the median size was 4 cm (Table 2).

Discussion

Renal angioembolization and surgery are both efficacious treatments for AML. In past series, surgery has been more prevalent,[sup.1,20,21] although there is a trend towards using more angioembolization at our centre and at other centres around the world.[sup.20] This trend most likely reflects improved angiography techniques and the desire to maintain maximal renal function. No study clearly demonstrates the superiority of one embolic agent. The agents appear to have similar rates of success, complications and postinfarction syndrome.[sup.22] With new materials, such as acrylic embospheres and hepaspheres continuously, emerging the preferred agents are likely to change over time.[sup.23]

The advantage of a surgical approach includes complete resection of the disease and pathologic analysis of the specimen to confirm the diagnosis. Where imaging strongly supports a diagnosis of AML, surgical treatment with simple enucleation is feasible and may reduce nephron loss. Angiomyolipoma is surrounded by a distinct pseudocapsule that permits enucleation through an avascular plane. One study reported 34 cases of successful enucleation for AML, although 3 cases required some sharp dissection due to difficulty in identifying the correct plane of enucleation. There was no evidence of recurrence after a median follow-up of 56 months, and no cases of urine leak as entry into the collecting system was largely avoided.[sup.24]

The advantages of RAE include preservation of renal function, minimal invasiveness of the procedure and rapid stabilization in cases of acute hemmhorage. Patients with AMLs that are fed by a distinct arterial branch are optimal candidates for RAE, as multiple branches are more technically difficult and increase the risk of embolizing normal renal tissue.[sup.24] Apart from this, there are no specific radiologic features that strongly support the use of RAE over surgery. Tumours with complex vascular anatomy or close proximity to the hilum may require discussion between the urologist and interventional radiologist to determine the optimal approach.

Five of the 11 surgical cases that had complete data underwent surgery for suspicion of malignancy. These were all relatively small neoplasms, averaging 3 to 4 cm in size, with no fatty component. Although it seems as if there are many misdiagnoses on imaging, it is a relatively small number considering the 10 years of renal mass presentations at a tertiary care centre. In fact, large series have shown that 5% of all AMLs do not contain fat.[sup.2] The remaining 6 AMLs underwent surgery for reasons including large tumours (total nephrectomy), failure of RAE and surgeon/patient preference.

Interestingly, more patients underwent radical nephrectomy than partial nephrectomy. This is far more than we would expect for a benign neoplasm, given the morbidity from potential renal insufficiency. In fact, there are very limited indications for nephrectomy for AML. These include AMLs that have replaced most renal parenchyma, cases with a strong suspicion of malignancy or cases in which renal-preserving treatment is not technically possible. The latter 2 indications for nephrectomy should be relatively rare. For instance, AMLs that are confused with RCCs are usually small lesions, as they are more likely to have minimal fat on imaging. These tumours are more likely amenable to a partial nephrectomy, thus avoiding radical nephrectomy. Secondly, AMLs not amenable to partial nephrectomy should first be considered for RAE. Total nephrectomy should only be considered if both options have been exhausted.

The disproportionately high number of surgical cases compared to RAE cases in this study partly reflects the retrospective nature of the study and the inherent selection bias. The surgical cohort was recruited based on postoperative AML pathology (several of whom had surgery for preoperative concerns of malignancy). Thus, many of these patients were not presenting for management of AML, but rather for management of a suspected malignancy, resulting in an overestimation of the role of surgery for AML.

There are no guidelines regarding follow-up after AML treatment. Our centre does not have a standardized protocol, but most practitioners obtain a single computed tomography (CT) scan or ultrasound 6 months after treatment. The RAE cases performed for acute hemmorhage have a follow-up CT scan within 24 to 48 hours, but subsequent follow-up is variable. Angiomyolipomas undergoing RAE may require more long-term follow-up as they typically diminish in size, but do not disappear.[sup.12]

Ideally, prospective studies comparing angiography and partial nephrectomy would help to better define the specific roles of surgery and RAE. Series with longer follow-up would also help assess rates of recurrence and re-treatment, as the current case series in the literature have follow-ups of less than 10 years.

Conclusion

Angioembolization allows rapid patient stabilization in cases of acute hemorrhage and good renal preservation in cases of multifocal AML. Renal angioembolization may also be preferred in masses >15 cm if partial nephrectomy is not feasible. Surgery should be performed in cases of diagnostic uncertainty. The less invasive nature of angioembolization has been a primary driving force of its increasing usage over the past 10 years, but the role of surgery is undeniable, if as yet not fully defined. Prospective randomized studies are needed to compare angioembolization and surgery to better define their indications in sporadic AML.

Competing interests: None declared.

This paper has been peer-reviewed.

References

1.. Nelson CP, Sanda MG. Contemporary diagnosis and management of renal angiomyolipoma. J Urol 2002;1684 Pt 1:1315-25.

2.. Willatt J, Francis IR. Imaging and management of the incidentally discovered renal mass. Cancer Imaging 2009;9Spec No A:S30-37.

3.. Castoldi MC, Dellafiore L, Renne G, et al. CT demonstration of liquid intratumoural fat layering in a necrotic renal cell carcinoma. Abdom Imaging 1995;20:483-5.

4.. Garin JM, Marco I, Salva A, et al. CT and MRI in fat-containing papillary renal cell carcinoma. Br J Radiol 2007;80:e193-5.

5.. Helenon O, Chretien Y, Paraf F, et al. Renal cell carcinoma containing fat: demonstration with CT. Radiology 1993;188:429-30.

6.. Lesavre A, Correas JM, Merran S, et al. CT of papillary renal cell carcinomas with cholesterol necrosis mimicking angiomyolipomas. AJR Am J Roentgenol 2003;181:143-5.

7.. Strotzer M, Lehner KB, Becker K. Detection of fat in a renal cell carcinoma mimicking angiomyolipoma. Radiology 1993;188:427-8.

8.. Bissler JJ, McCormack FX, Young LR, et al. Sirolimus for angiomyolipoma in tuberous sclerosis complex or lymphangioleiomyomatosis. N Engl J Med 2008;358:140-51.

9.. Boorjian SA, Frank I, Inman B, et al. The role of partial nephrectomy for the management of sporadic renal angiomyolipoma. Urology 2007;70:1064-8.

10.. Fazeli-Matin S, Novick AC. Nephron-sparing surgery for renal angiomyolipoma. Urology 1998;52:577-83.

11.. Heidenreich A, Hegele A, Varga Z, et al. Nephron-sparing surgery for renal angiomyolipoma. Eur Urol 2002;41:267-73.

12.. Williams JM, Racadio JM, Johnson ND, et al. Embolization of renal angiomyolipomata in patients with tuberous sclerosis complex. Am J Kidney Dis 2006;47:95-102.

13.. Bissler JJ, Racadio J, Donnelly LF, et al. Reduction of postembolization syndrome after ablation of renal angiomyolipoma. Am J Kidney Dis 2002;39:966-71.

14.. Jacobson AI, Amukele SA, Marcovich R, et al. Efficacy and morbidity of therapeutic renal embolization in the spectrum of urologic disease. J Endourol 2003;17:385-91.

15.. Kennelly MJ, Grossman HB, Cho KJ. Outcome analysis of 42 cases of renal angiomyolipoma. J Urol 1994;1526 Pt 1:1988-91.

16.. Lee SY, Hsu HH, Chen YC, et al. Evaluation of renal function of angiomyolipoma patients after selective transcatheter arterial embolization. Am J Med Sci 2009;337:103-8.

17.. Lenton J, Kessel D, Watkinson AF. Embolization of renal angiomyolipoma: immediate complications and long-term outcomes. Clin Radiol 2008;63:864-70.

18.. Hamlin JA, Smith DC, Taylor FC, et al. Renal angiomyolipomas: long-term follow-up of embolization for acute hemorrhage. Can Assoc Radiol J 1997;48:191-8.

19.. Kim JK, Park SY, Shon JH, et al. Angiomyolipoma with minimal fat: differentiation from renal cell carcinoma at biphasic helical CT. Radiology 2004;230:677-84.

20.. Seyam RM, Bissada NK, Kattan SA, et al. Changing trends in presentation, diagnosis and management of renal angiomyolipoma: comparison of sporadic and tuberous sclerosis complex-associated forms. Urology 2008;72:1077-82.

21.. Tsai HN, Chou YH, Shen JT, et al. The management strategy of renal angiomyolipoma. Kaohsiung J Med Sci 2002;18:340-6.

22.. Schwartz MJ, Smith EB, Trost DW, et al. Renal artery embolization: clinical indications and experience from over 100 cases. BJU Int 2007;99:881-6.

23.. Bilbao JI, de Luis E, Garcia de Jalon JA, et al. Comparative study of four different spherical embolic particles in an animal model: a morphologic and histologic evaluation. J Vasc Interv Radiol 2008;19:1625-38.

24.. Minervini A, Giubilei G, Masieri L, et al. Simple enucleation for the treatment of renal angiomyolipoma. BJU Int 2007;99:887-91.

Tables

Table 1.: Case characteristics of angiomyolipoma treated at Vancouver General Hospital (1999-2009) [Table omitted]

Table 2.: Characteristics of angiomyolipoma surgical specimens [Table omitted]

Table 3.: Embolic agents used for renal angioembolization [Table omitted]

Author Affiliation(s):

[1] Department of Urologic Sciences, University of British Columbia, Vancouver, BC

Correspondence: Dr. Alan So, Department of Urologic Sciences, University of British Columbia, Level 6 Urology, 2775 Laurel St., Vancouver, BC V6Z 1M5; dralanso@interchange.ubc.ca
Gale Copyright: Copyright 2011 Gale, Cengage Learning. All rights reserved.