**1. Introduction**

[8] Van Poppel H, Da Pozzo L, AlbrechtW, et al. A prospective randomized EORTC inter‐ group phase 3study comparing the complications of elective nephron-sparing surgery and radical nephrectomy for lowstage renal cell carcinoma. Eur Urol 2007; 51: 1606–1615.

[9] Van Poppel H, Da Pozzo L, AlbrechtW, et al. A prospective, randomized EORTC in‐ tergroup phase 3 study comparing the oncologic outcome of elective nephron-spar‐ ing surgery and radical nephrectomy for low-stage renal cell carcinoma. Eur Urol

[10] Van Poppel H, Becker F, Cadeddu J, et al. Treatment of localized Renal cell Carcino‐

[11] Sobin L, Wittekind Ch. TNM Classification of Malignant Tumours. New York, John

[12] Fuhrman SA, Lasky LC, Limas C. Prognostic significance of morphologic parameters

[13] Patard J-J, Pantuck AJ, Crepel M, et al. Morbidity and clinical outcome of nephronsparing surgery in relation to tumour size and indication. Eur Urol 2007; 52: 148–154.

[14] Leibovich BC, Blute ML, Cheville JC, Lohse CM, Weaver AL, Zincke H. Nephron sparing surgery for appropriately selected renal cell carcinoma between 4 and 7 cm results in outcome similar to radical nephrectomy. J Urol 2004; 171: 1066–1070.

[15] Dash A, Vickers AJ, Schachter LR, Bach AM, Snyder ME, Russo P. Comparison of outcomes in elective partial vs radical nephrectomy for clear cell renal cell carcinoma

[16] Becker F, Siemer S, Hack M, Humke U, Ziegler M, Stockle M. Excellent long-term cancer control with elective nephron-sparing surgery for selected renal cell carcino‐

[17] Pahernik S, Roos F, Röhrig B, et al. Elective nephron sparing surgery for renal cell

[18] Antonelli A, Cozzoli A, Nicolai M, et al. Nephron-sparing surgery versus radical nephrectomy in the treatment of intracapsular renal cell carcinoma up to 7 cm. Eur

[19] Joniau S, Vander Eeckt K, Srirangam SJ, Van Poppel H. Outcome of nephron-sparing

[20] Badalato GM, Kates M, Wisnivesky JP, Choudhury AR, McKiernan JM. Survival after partial and radical nephrectomy for the treatment of stage T1bN0M0 renal cell carci‐ noma (RCC) in the USA: a propensity scoring approach. BJU Int 2012; 109: 1457-1462.

[21] Ficarra V, Novara G, Secco S, et al. Preoperative aspects and dimensions used for an anatomical (PADUA) classification of renal tumours in patients who are candidates

surgery for T1b renal cell carcinoma. BJU Int 2009; 103: 1344–1348.

for nephron-sparingsurgery. Eur Urol 2009; 56: 786–793.

in renal cell carcinoma. Am J Surg Pathol. 1982; 6: 655-663.

mas measuring more than 4 cm. Eur Urol 2006; 49: 1058–64.

carcinoma larger than 4 cm. J Urol 2008; 179: 71–74.

2011; 59: 543–552.

94 Renal Tumor

ma Eur. Urol 2011; 60: 662-672.

Wiley & Sons. 2002; vol. 6. p. 193.

of 4-7 cm. BJU Int 2006; 97: 939–945.

Urol 2008; 53: 803–809.

Role of renal artery embolization (RAE) in strategy of treatment of renal carcinoma (RC) has a multiyear history in scientific literature and in personal experience. In view of personal ex‐ perience we have a strong feeling that RAE is beneficial both in operable and advanced RC, partially because of longer survival and stimulation of certain immune reactions [1].

RAE was introduced to clinical practice in the 70's of last century. The pioneers who devel‐ oped the technique of surgery were Lalli et al, in 1973 while Almgard et al. presented their own experience with the application of RAE in renal cancer in humans [2,3]. At that time arteriography was the basic diagnostic methods and identification of renal tumors was made during the embolization. Today, vascular embolization procedures are becoming widely used in the treatment of persistent bleeding, vascular defects and cancer.

In urology RAE is well established in the treatment of bleeding observed after jatrogennie complications of NSS (nephron sparing surgery), PCN (percutaneous nephrostomy), ESWL (extracorporeal shock wave lithotripsy), PCNL (percutaneous nephrolithotrypsy), closing arteriovenous fistulas and the need to rempve kidney in the case of severe nephrotic syn‐ drome or secondary arterial hypertension [4, 7, 22].

Basic form of treatment of locoregional RC is surgical resection of kidney containing the tumor (optionally with adrenal gland and extraperitoneal lymph nodules). Recently it is adviced to introduce new, less invasive surgical techniques (laparoscopy and use of ro‐ bots), as well as NSS (nephron sparing surgery). These techniques are used mostly in less advanced RC (T1) [25, 28, 29, 30].

In the strategy of treatment of more advanced RC frequently there is adviced application of RAE [2,3]. RAE is a procedure based on introduction, with use of an angiographic catheter,

into blood vessel an obstruction material aimed to interrupt blood supply to an organ or to its particular region. At present different coils, haemostatic spongues, cyanoacrylic glues and alcohols are applied as materials for RAE [2, 11, 19]. This leads to acute necrosis of tis‐ sues where blood flow has been amputeed, which in turn results in development of acute phase reaction in the organism.

system in patients with RC undergoing RAE [14]. We analyzed 50 patients with RC ex‐ ceeding diameter of 7 cm (T≥2) and tested immune status of persons with less and more advanced RC. 30 patients underwent palliative RAE and assessment of immune status at different times after embolization. The complex assessment of immune status included large battery of microculture tests of peripheral blood mononuclear cells (PBMC), estima‐ tion of levels of certain cytokines and cytometric measurement of lymphocyte subpopula‐ tions in peripheral blood. It was found that RAE lowers the suppressive action of neoplastic cells on the immune system, results in normalization of disordered proportion of lymphocyte subpopulations (CD4, CD8) and enhances the antiinflamatory response (increases levels of certain cytokines- IL-10 and IL-1ra). All together, the result reveal stimulation of certain functions of immunocompetent cells isolated from blood of RAEtreated RC patients. Clinical relevance of these findings and concluding whether or not

Renal Artery Embolization in Treatment of Renal Cancer with Emphasis on Response of Immune System

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The initial indications developed in the 1970s for RAE were limited to symptomatic haema‐ turia and palliation for metastatic renal cancer [2,3]. With technical advances and growing experience the indications have broadened to include conditions such as vascular malforma‐ tions, medical renal disease, angiomyolipomas (AMLs), and preoperative infarction. The in‐ troduction of smaller delivery catheters and more precise embolic agents has drastically improved the morbidity associated with this technique [4]. RAE has continued to gain popu‐

The technique of embolising hypervascular renal carcinomas dates back to 1969 when first reported by Lalli et al [2]. Since then, various techniques and embolic materials have been described. RAE has been used pre-operatively to facilitate nephrectomy [8], or to stimulate a possible systemic response in patients with metastases [5]. Renal embolisation has been es‐ tablished as a palliative treatment for unresectable renal carcinoma and in patients with less advanced disease (stage I–III) who, for whatever reason, are unsuitable or unwilling to un‐ dergo surgery [18, 22, 24]. In this group of patients the technique reduces tumour bulk and

However, opinions on the role of preoperative RAE in the management of patients with RC are controversial. Although a significant number of studies on RAE are reported in these patients, there is no consensus on the benefits and morbidity associated with the

Effective embolization induces acute ischemic necrosis zone to form infarct of the organ tis‐ sues, which results in the onset of symptoms called postembolization syndrome, which usu‐ ally occurs within the first few days after RAE [8]. Greater risk of developing the postembolization syndrome occurs in patients with small tumors, developing peripherally, when still remains a large part of the normal, not embolized part of the kidney [9]. The side effects which occur after RAE include: pain in the lumbar region, nausea and vomiting, hy‐

RAE improved immune status of patients needs further studies.

larity as a minimally invasive approach for various urological conditions.

relieves local symptoms such as pain or intractable haematuria.

procedure [7-9].

**2. Techniques of renal artery embolization**

RAE is applied in treatment of RC for about 40 years [3]. It may be evoked prior to surgery, considered as a technique succouring the surgery, or used as palliative embolization in large, inoperable RC, mostly with intensive bleedings and/or pains. RAE which preceedes nephrectomy provides better conditions for the surgery and allows to shorten time of the intervention [1,4]. There exist informations that RAE may lead to stabilization and/or regres‐ sion of distal metastases. These effects may be due to immunomodulating effects of RAE suggested by some authors [1,5]. However, knowledge on influence of RAE on immune sta‐ tus and response of immunocompetent cells is still scarce and fragmentaric. Systematic stud‐ ies of this issue are needed.

In view of multiple limitations in efficacy and safety of RAE the present indications for ap‐ plication of this procedure include mostly [6, 7, 18]:


Opinions on the role of preoperative RAE in the management of patients with RC are con‐ troversial. Although a significant number of studies on RAE are reported in RC patients, there is no consensus on the benefits and morbidity associated with the procedure [7, 22]. Moreover, many large studies on the use of RAE both prior to nephrectomy and in ad‐ vanced RC were conducted in the 1980s, before the development of improved techniques and imaging. Most proponents of preoperative RAE report the facilitation of nephrectomy through decreased operative blood loss, ease of dissection secondary to the development of oedema in tissue planes, and decreased operative time [8,9]. For those patients with signifi‐ cant tumour thrombus there might be a beneficial effect of decreasing the size or extent of tumour thrombus before surgery [10]. Interestingly, there might also be an advantage in the form of immunomodulation, whereby RAE-induced tumour necrosis stimulates a tumourspecific response from the immune system of the host [11-13].

Own experience [1] includes 474 patients with RC of which 118 had RAE before nephrec‐ tomy. It was reported that RAE significantly prolonged survival time in T2 and T3 RC. Additionally, it was found preliminarly that RAE exerted immunotropic effects and en‐ hanced immune status of the patients. This diminished risks of the surgery. Recently we‐ continued these investigations and performed series of studies on response of immune system in patients with RC undergoing RAE [14]. We analyzed 50 patients with RC ex‐ ceeding diameter of 7 cm (T≥2) and tested immune status of persons with less and more advanced RC. 30 patients underwent palliative RAE and assessment of immune status at different times after embolization. The complex assessment of immune status included large battery of microculture tests of peripheral blood mononuclear cells (PBMC), estima‐ tion of levels of certain cytokines and cytometric measurement of lymphocyte subpopula‐ tions in peripheral blood. It was found that RAE lowers the suppressive action of neoplastic cells on the immune system, results in normalization of disordered proportion of lymphocyte subpopulations (CD4, CD8) and enhances the antiinflamatory response (increases levels of certain cytokines- IL-10 and IL-1ra). All together, the result reveal stimulation of certain functions of immunocompetent cells isolated from blood of RAEtreated RC patients. Clinical relevance of these findings and concluding whether or not RAE improved immune status of patients needs further studies.
