Experience of Renal Artery Embolization Prior to Nephrectomy

Original article

Diego Alejandro Arboleda-Gómez1 Johan Sebastián Lopera-Valle2 Luisa Fernanda Rueda-Cárdenas3 Juliana Andrea Vergara-Cadavid4 José Miguel Hidalgo-Oviedo5

1 Radiologist, Hospital Universitario San Vicente Fundación, Medellín, Colombia. 2 Radiology Resident, Universidad de Antioquía, Medellín, Colombia. 3 Clinical Neurology Resident, Universidad CES, Medellín, Colombia. 4 Physician, University of Antioquía, Medellín, Colombia. 5 Interventional Radiologist, University Hospital San Vicente fundación, Medellín, Colombia

Abstract Aim To describe the perioperative progress of patients undergoing nephrectomy with and without preoperative Renal Artery Embolization (RAE) in a high-complexity hospital in Medellín, Colombia. Materials and Methods. Retrospective, descriptive and observational study. Patients aged 18–90 years old with a diagnosis of renal tumor and who underwent nephrectomy with and without preoperative RAE were included. Qualita- tive variables were expressed as rates and proportions, and quantitative variables were expressed by measures of central tendency and dispersion. Results Seventy-one patients with a mean age of 58.1 (SD: 10.6) years were included; 41 were women and 69% were diagnosed with clear-cell carcinoma. The mean intraoperative blood loss was 540.8 cc, and 19.7% required transfusion. The average operative time was 2.6 hours and 38% had complications, with a total mortality of 4.2%. When comparing patients with RAE (15 patients) versus patients without RAE (56 patients), higher intraoperative blood loss and transfusion requirements were identified in the former. Conclusion Patients undergoing RAE had greater blood loss, transfusion rates and postoperative complications. Thus, a consensus is needed on the actual therapeutic relevance of this procedure. Keywords therapeutic embolization, nephrectomy, kidney neoplasms, renal artery

Introduction of renal angiomyolipoma.4 Benefits warranting the use of this technique include a decrease in perioperative blood loss, cre- The 5-year survival rate for kidney cancer has increased over ation of a tissue plane of edema facilitating dissection, reduc- time both for localized disease (from 88.4% during 1992- tion in tumor bulk and extent of vascular thrombus, when 1995 to 91.8% during 2004-2010) and advanced disease present.5-7 (from 7.3% during 1992-1995 to 12.3% during 2004-2010), Even if RAE prior to nephrectomy has been described in which might be attributed to recent advances in minimally the literature as a safe procedure with potential periopera- invasive treatment options.1 Thus, renal artery embolization tive benefits, to date there is no consensus to promote the (RAE), first described in 1969 by Lalli and Peterson, initially routine use of this procedure. 6-8 It is noteworthy that in our indicated in the symptomatic treatment of hematuria and in setting RAE is no longer being used for kidney tumor man- palliation of metastatic renal cancer2, had its use broadened agement, probably because of the discrepancy found in some in the 1970s, and initial interest in the technique resulted in series and the consequent debate over its actual impact on multiple published series in 1980 and 1990.3 clinical outcome. The aim of this study is to describe the peri- At present, indications for RAE for the management of re- operative progress of patients undergoing nephrectomy with nal masses include preoperative adjunctive treatment before and without a preoperative RAE and who received medical nephrectomy for primary masses, palliation of symptoms re- care at our institution between 2009 and 2016. lated to advanced renal cell carcinoma and primary treatment

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Materials and methods medical records were collected in the forms and stored in a da- tabase previously designed by the team conducting the study. A retrospective, descriptive and observational study was per- The plan of analysis was based on the objectives of the study. formed. The study included all patients aged 18 to 90 years Qualitative variables were expressed as rates and proportions, old with a diagnosis of renal tumor by computed tomography and quantitative variables were expressed as means and stan- or histology who had undergone radical nephrectomy with dard deviation (SD), or median (Mdn) and interquartile range or without complete preoperative embolization of the renal (IQR) according to their distribution. Data collected were ana- artery in a high-complexity hospital in the city of Medellín, lyzed using SPSS Statistics 20.0. Colombia between 2009 and 2016. The indication for RAE This research study was approved by the Institutional Ethics was considered as preoperative adjunctive treatment before Committee and conducted in accordance with the ethical nephrectomy for primary kidney masses and there were no principles for research, in compliance with the Declaration of exclusion criteria. Helsinki and with resolution No. 008430 issued in 1993 by The technique employed was percutaneous transcatheter the Ministry of Health of Colombia. embolization by ultrasound-guided femoral artery access via a vascular sheath (5Fr x 11 cm) with Seldinger’s technique and a micropuncture set, using a hydrophilic guidewire Results (0.035” x 150 cm) and Cobra catheter (5Fr). Thus, mechani- cal occlusion of the vascular territory of interest was achieved The study included a total of 71 patients with a mean age of (complete renal embolization) with 2-3 vials of polyvinyl al- 58.1 years old (SD: 10.6), of which 41 were females (57.7%). cohol microparticles with a particle size of 300-500 microns Only 15 of these patients underwent RAE prior to nephrec- or 700-1000 microns (Fig. 1). In addition, non-ionic water- tomy within the period considered for this study, with a time soluble iodinated contrast medium at 300 mg/ml and Philips no longer than 72 hours between embolization and surgery. Allura Xper FD10 angiographic equipment were used. Table 1 shows the baseline characteristics of patients, with a Radical nephrectomy was performed by the group of sur- higher proportion of clear-cell carcinoma in patients not un- geons of the institution, who also recorded intraoperative dergoing preoperative RAE. All patients had a platelet count variables such as blood loss on the surgery report. above 100,000/ml and an INR less than 1.5 before undergo- Socio-demographic, clinical and surgical characteristics were ing surgery. recorded on a data collection form designed by the investi- As regards the oncologic features of the 71 patients as a gators for this specific purpose. Relevant data obtained from whole, 69% (n = 49) had a histologic diagnosis of clear-cell

Fig. 1 Coronal arterial phase computed tomography (CT) reconstruction (A) and pre- (B) and post- (C) RAE images in a patient with clear-cell renal carcinoma of the right kidney upper pole (arrow in A) employing a percutaneous transcatheter embolization technique via femoral access with PVA microparticles. Angiographically, the tumor mass has newly formed vessels with increased blood supply (arrow in B). The post-embolization follow-up image shows satisfactory results with occlusion of the vascular territory of interest and absence of intra-parenchymal contrast (arrow in C).

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Table 1: Baseline characteristics of the patients undergoing Table 2: Oncologic characteristics of all 71 patients. nephrectomy with and without preoperative RAE.

Variable WITH RAE WITHOUT RAE Type of renal tumor % (n) (n = 15) (n = 56) Clear-cell carcinoma 69 (49) Chromophobic carcinoma 9.9 (7) Age [X (SD)] 58.3 (10.4) 59.2 (9.6) Collecting duct tumor 2.8 (2) Female gender [% (n)] 73.3 (11) 53.5 (30) Sarcomatoid tumor 2.8 (2) Angiomyolipoma 2.8 (2) Type of renal tumor Other 12.7 (9) Clear-cell carcinoma [% (n)] 33.3 (5) 78.5 (44) Chromophobic carcinoma [% (n)] 13.3 (2) 8.9 (5) Tumor stage % (n) Collecting duct tumor [% (n)] 6.6 (1) 1.7 (1) Size Sarcomatoid tumor [% (n)] 6.6 (1) 1.7 (1) T1 43.7 (31) Angiomyolipoma [% (n)] 6.6 (1) 1.7 (1) T2 19.7 (14) Others [% (n)] 20 (3) 10.7 (6) T3 26.8 (19) Tumor stage T4 9.9 (7) Stage T3-4 [% (n)] 53.3 (8) 32.1 (18) Nodule/Lymph node Stage N2-3 [% (n)] 26.6 (4) 14.2 (8) Nx 59.2 (42) Stage M1 [% (n)] 33.3 (5) 17.8 (10) N0 23.9 (17) N1 16.9 (12) Abbreviations: SD, Standard deviation; X, Mean. Metastasis Mx 25.4 (18) M0 53.5 (38) M1 21.1 (15) carcinoma, in over half of the patients (63.4%) the tumor Discussion was limited to the kidney (T1 and T2). Only 12 patients had confirmed spread into regional lymph nodes (N1), and 15 had In the United States, renal cell carcinoma constitutes approxi- metastatic disease (M1) (Table 2). mately 3.9% of new cancers, with a mean age of 64 years at Table 3 shows the perioperative characteristics of patients, with a diagnosis and a male:female ratio of 2:1.1 It should be noted mean postoperative follow-up of 11 days (SD: 2.7). The mean intra- that the mean age of the patients included in this study was operative blood loss was 540.8 cc and 19.7% of patients (n = 14) 58.1 years, being slightly higher in women (male:female ratio required transfusion of blood products with a mean of 2.7 units of of 1.3:1). According to literature reports, in 50% of cases the red blood cells. The average operative time was 2.6 hours and post- tumor stage at presentation is T1-T2,9 which is similar to the operative complications were documented in 38% of patients (n = findings reported above, with near 60% of tumors belonging 27), with mortality that may be attributed to the surgical procedure to those stages. performed in three patients (4.2%) in the group without RAE. Opinions on the role of preoperative RAE in the management As regards the postoperative complications of all 71 patients of patients with kidney tumors remain controversial,5 and undergoing nephrectomy, the most common was acute renal the literature still shows no consensus on the benefits and failure in six patients, followed by ileus and lumbar pain in morbidity associated with this procedure.9-11 Even if facilita- 7% each (n = 5). It should be noted that none of the patients tion of nephrectomy through decreased blood loss, ease of undergoing RAE had gross hematuria or anemia secondary dissection secondary to edema in tissue planes and decreased to the procedure. operative times have been reported with RAE,2,12, this study When comparing perioperative variables, intraoperative showed a tendency to greater intraoperative blood loss and blood loss values, transfusion requirements (Table 3) and needs for transfusion in patients undergoing embolization postoperative lumbar pain (Table 4) are greater in patients prior to nephrectomy. undergoing RAE.

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Table 3: Perioperative variables in patients undergoing nephrec- Table 4: Complications in patients undergoing nephrectomy with tomy with and without preoperative RAE. and without preoperative RAE.

Variable All WITH WITHOUT Variable WITH RAE WITHOUT RAE patients RAE RAE (n =15) (n = 56) (n = 71) (n = 15) (n = 56) Intraoperative bleeding 540.8 896 445.7 HTN [% (n)] 6.6 (1) 3.5 (2) (cc) [X (SD)] (729.2) (729) (705.6) Lumbar pain [% (n)] 20 (3) 3.5 (2) Fever [% (n)] 0 (0) 5.3 (3) Need for transfusion 19.7 (14) 40 (6) 14.2 (8) Ileus [% (n)] 6.6 (1) 7.1 (4) [% (n)] SSI [% (n)] 0 (0) 7.1 (4) Number of units of PRBCs 2.7 (1) 2.83 (0.9) 2.63 (1.1) AKI [% (n)] 0 (0) 10.7 (6) [X (SD)] Others [% (n)] 6.6 (1) 8.9 (5)

Operative time (hours) 2.6 (1.1) 2.9 (1.4) 2.6 (1) Abbreviations: HTN, hypertension; AKI, acute kidney injury; SSI, [X (SD)] surgical site infection. POP complications [% (n)] 38 (27) 40 (6) 29.6 (21) Others: nephrocutaneous fistula, perinephric collections, vascular lesions and pneumonia. POP mortality [% (n)] 4.2 (3) 0 (0) 5.3 (3) Abbreviations: SD, standard deviation; POP, postoperative; PRBC, packed red cells; X, mean.

The results reported above are not consistent with those number of units transfused, a longer operative time, more reported by other authors, such as Maksimov et al.13, who perioperative complications and increased mortality. described their experience with superselective balloon em- RAE is considered a safe procedure with low mortality.18,19 bolization of segmental branches of the renal artery prior to Complications reported include, but are not limited to, surgi- partial nephrectomy for renal malignancy. These authors ob- cal site infection, retroperitoneal abscesses, cardiopulmonary served an average decrease in intraoperative blood loss and events, secondary hemorrhage, blood transfusion, thrombo- surgical times. Yeast et al.14 evaluated intraoperative blood sis, stroke, ileus, post-embolization syndrome and inguinal loss and transfusion rates in patients undergoing transplant hematoma. The most serious complications affect between nephrectomy with (group 1) and without (group 2) preopera- 2% and 10% of patients, with a mortality rate of 3.3%. tive embolization. The mean blood loss for patients receiving The most common serious complication is post-embolization embolization was 143.9 cc versus 621.4 cc in group 2 (p = syndrome, characterized by lumbar pain, fever and nauseas, 0.041). Finally, Ángeles et al.15 reported lower intraoperative which has been reported in up to two-thirds of patients un- blood loss and higher survival rates in 23 patients in Mexico dergoing RAE.20,21 who underwent embolization prior to nephrectomy com- In this study, the overall rate of complications with and with- pared to 98 patients who did not receive embolization. out RAE prior to nephrectomy was about 38% (n = 27), with On the other hand and similarly to our findings, May et al.16 no cases of mortality associated with the embolization pro- did not find significant differences in mortality or surgical cess. Zargar et al.8, in their series of 42 patients undergoing complications in the study performed between 1992 and RAE prior to radical nephrectomy between 2004 and 2011, 2006 in 834 patients, after comparing 227 patients undergo- of which 7 in 10 patients had advanced stage disease (T3 and ing nephrectomy with preoperative RAE (group 1) versus 607 T4), documented surgical complications in 45.2%. patients undergoing nephrectomy alone (group 2). These au- As previously mentioned when discussing results, the rates thors also reported higher blood transfusion requirements in obtained were 8.5% for acute renal failure (as compared to group 1 vs. group 2 (61% vs. 24%, p <0.01), which is similar 2% reported by Zielinski et al.23), 7% for ileus (9% was re- to our findings. Subramanian et al.17 concluded in 2009 that ported by Zielinski et al.23), 7% for lumbar pain (86% was preoperative embolization of the renal artery in 135 patients documented by Zielinski et al.23), 5.6% for SSI (8.6% was undergoing radical nephrectomy did not provide any measur- reported by May et al.16), 4.2% for hypertension (75% was able benefit, but instead was associated with a greater mean reported by Zielinski et al.23 and 51.5% by Pascual et al.24),

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and 4.2% for fever (58% was reported by Zielinski et al.23). G Chir. 2013;34(9-10):263–266 3 Almgård LE, Slezak P. Treatment of renal adenocarcinoma by emboliza- The main limitations of this study are those related to an tion: a follow-up of 38 cases. Eur Urol. 1977;3(05): 279–281 observational, descriptive, retrospective design with a small 4 Li D, Pua BB, Madoff DC. Role of embolization in the treatment of renal sample. However, it is worth noting that this type of inter- masses. Semin Intervent Radiol. 2014;31(01):70–81 5 Madoff D, Verma R, Ahrar K. Embolotherapy for organ ablation. In: Gol- vention is now rarely performed, which is consistent with zarian J, Sun S, SharafuddinM(eds.) Vascular Embolotherapy. A Compre- the small series reported in 2016 by Maksimov et al.13 (11 hensive Approach. Heidelberg: Springer-Verlag; 2016: 201–220 14 6 Muller A, Rouvière O. Renal artery embolization-indications, technical ap- patients) and by Yeast et al. (16 patients), and in 2016 by proaches and outcomes. Nat Rev Nephrol. 2015;11 (05):288–301 Thorlund et al.21 (15 patients). 7 Ramaswamy RS, Darcy MD. Arterial Embolization for the Treatment of It should also be mentioned that there may be a potential Renal Masses and Traumatic Renal Injuries. Tech Vasc Interv Radiol. 2016;19(03):203–210 bias in the selection of patients for this study, considering 8 Zargar H, Addison B, McCall J, Bartlett A, Buckley B, Rice M. Renal artery the absence of clear criteria for performing RAE, whose indi- embolization prior to nephrectomy for locally advanced renal cell carcinoma. ANZ J Surg. 2014;84(7-8):564–567 cation was considered appropriate by the treating physician 9 Martínez A, Sánchez LC, Calderón JE, Domínguez GL, Pedraza H, Ávila as preoperative adjunctive treatment before nephrectomy for P. Comparación del tratamiento quirúrgico de los tumores renales con embolización y sin embolización de la arterial renal. Bol Coleg Mex Urol. primary kidney masses. In addition, a higher percentage of 2010;25(02):82–90 patients receiving RAE had a more advanced stage of disease, 10 Keller FS. Interventional radiology: new paradigms for the new millen- which might have been a confounding variable in the mea- nium. J Vasc Interv Radiol. 2000;11(06):677–681 11 Rimon U, Duvdevani M, Garniek A, Golan G, Bensaid P, Ramon J, et al. surement of operative time, blood loss and complications. Ethanol and polyvinyl alcohol mixture for transcatheter embolization of In conclusion, in our study, patients undergoing RAE had renal angiomyolipoma. AJR Am J Roentgenol. 2006;187(03):762–768 12 Qin C, Wang Y, Li P, Li P, Tao J, Shao P, et al. Super-Selective Artery Embo- higher blood loss, a higher rate of transfusions and postop- lization before Laparoscopic Partial Nephrectomy in Treating Renal Angio- erative complications, with the actual impact of RAE on rel- myolipoma. Urol Int. 2017;99(03): 277–282 evant surgical and clinical outcomes still being controversial. 13 Maksimov AV,Martov AG, Pavlov LP, Neustroev PA, Vinokurov RR. [Lapa- roscopic partial nephrectomy with superselective balloon embolization of Even if with this study design no evidence can be obtained to renal artery]. Urologiia. 2017;1(01):31–36 set clear guidelines for the surgical management of the study 14 Yeast C, Riley JM, Holyoak J, RossG Jr,Weinstein S,WakefieldM.Use of preoperative embolization prior to Transplant nephrectomy. Int Braz J Urol. population, this is a first step in regional epidemiology and it 2016;42(01):107–112 encourages further studies on the performance of different 15 Ángeles A, Sánchez LC, Calderón JE, Domínguez G, Lujano H, Ávila P. techniques and embolizing agents according to their avail- Comparación del tratamiento quirúrgico de los tumores renales con em- bolización y sin embolización de la arterial renal. Bol Coleg Mex Urol. ability, affordability and costs. 2010;25:82–90 16 May M, Brookman-Amissah S, Pflanz S, Roigas J, Hoschke B, Kendel F. Pre-operative renal arterial embolisation does not provide survival benefit in patients with radical nephrectomy for renal cell carcinoma. Br J Radiol. Ethical responsibilities 2009;82(981):724–731 17 Subramanian VS, Stephenson AJ, Goldfarb DA, Fergany AF, Novick AC, Protection of human subjects and animals. The authors Krishnamurthi V. Utility of preoperative renal artery embolization for declare that no experiments were performed on humans or management of renal tumors with inferior vena caval thrombi. Urology. animals for this investigation. 2009;74(01):154–159 18 Schwartz MJ, Smith EB, Trost DW, Vaughan ED Jr. Renal artery emboli- Confidentiality of data.The authors declare that they have zation: clinical indications and experience from over 100 cases. BJU Int. followed the protocols of their work center on the publica- 2007;99(04):881–886 19 Ginat DT, Saad WE, Turba UC. Transcatheter renal artery embolization of patient data. tion: clinical applications and techniques. Tech Vasc Interv Radiol. Right to privacy and informed consent. The authors de- 2009;12(04):224–239 clare that no patient data appear in this article. 20 Guziski M, Kurcz J, Tupikowski K, Antosz E, Słowik P, Garcarek J. The Role of Transarterial Embolization in the Treatment of Renal Tumors. Adv Clin Exp Med. 2015;24(05):837–843 Conflicts of interest 21 Thorlund MG, Wennevik GE, Andersen M, Andersen PE, Lund L. High suc- cess rate after arterial renal embolisation. Dan Med J. 2015;62(05):1–3 The authors declare no conflicts of interest. 22 Gueglio G, Piana M, García R, Peralta O, Damia O. Lugar actual de la embolización transarterial en tumores renales. Rev Argent Urol. References 2005;70(01):31–41 23 ZielinskiH, Szmigielski S, Petrovich Z. 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