Transarterial Nephrectomy: The Current Status of Experimental and Clinical Studies

Abstract

Open nephrectomy is associated with significant morbidity. For several years, minimally invasive alternatives have been developed such as laparoscopic nephrectomy or transarterial renal ablation. This paper focuses on the different principles of vaso-occlusion and further improvements of the technique such as capillary chemoembolization in experimental as well as clinical studies. Based on own in vitro studies, the principle of capillary embolization with occlusion of the entire arterial system up to the capillaries by a precipitating corn protein (Ethibloc) has been developed in animal studies (i.e., rat and canine kidney model). The precipitation speed of Ethibloc can be prolonged by 40% glucose per injection. The organ-ablative efficacy was evaluated in models of unilateral hypertension and chemically induced renal tumors (i.e., dimethyl-nitrosamine). Further studies using the model of unilateral transarterial implantation of Yoshida-sarcoma cells compared capillary chemoembolization using Ethibloc/mitomycin C (MMC) versus chemoperfusion and capillary embolization. Before starting clinical trials, the optimal mixture of Ethibloc and MMC was determined in vitro and in vivo. Prior to the vaso-occlusion, the volume of the arterial system of the kidney is determined by perfusion of the kidney with contrast-dye via a blocked balloon-catheter. Then 25% of the determined volume of 40% glucose is pre-injected followed by Ethibloc/MMC being injected with 1-cm(3) syringes. Once the capillary bed and tumor sinusoids are reached, the balloon catheter is emptied by postinjection of 40% glucose. Capillary embolization proved to be significantly superior to a central (i.e., ligation of renal artery) or peripheral type of occlusion resulting in complete coagulation necrosis of the normal rat and canine kidney with reduction of the elevated blood pressure, similar to nephrectomy in the model of renal hypertension. In the model of chemically induced renal tumors, complete necrosis of T2 stages could be achieved in 83% using Ethibloc compared to only 63% with Gelfoam particles, and 17% after ligation. In T3/T4 stages, the response rate was only 60% versus 0% after central and peripheral occlusion. In the highly aggressive Yoshida-sarcoma model, capillary chemoembolization yielded an 80% complete response rate compared to only 75% after capillary embolization and 70% after chemoperfusion. The optimal mixture of Ethibloc and MMC ranged between 1 and 2 mg of MMC to 1 cm(3) of Ethibloc, therefore for clinical trials 10 mg MMC was added to the 7.5 cm(3) syringe of Ethibloc. Clinical studies included 68 preoperatively as well as 62 palliatively embolized patients with renal cell carcinoma. The procedure was relatively well tolerated and usually associated with a mild postembolization syndrome. After an interval of up to 28 days, complete necrosis of the renal tumor could be achieved in tumors up to 9 cm in diameter. Hematuria ceased in all cases, and in selected cases long-lasting responses of very large tumors (i.e., vena cava involvement) could be achieved. Capillary chemoembolization represents an effective concept for ablation of malignant renal tumors. It offers control of tumor growth in case of temporary inoperability as well as cessation of hematuria in a palliative situation. Because of the local ablative efficiency, it may still represent a minimally invasive option in advanced stages of renal carcinoma (i.e., in combination with immunochemotherapy or targeted therapy).