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Science to Practice |
Mallinckrodt Institute of Radiology, Washington University School of Medicine, 510 S Kingshighway Blvd, St Louis, MO 63110. darcym@mir.wustl.edu
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While hepatic embolization has clear benefits, embolotherapy is less often applied to renal cancers. Agents like ethanol fail to ablate all malignant renal tissue (1), and there are reasonable minimally invasive surgical alternatives (eg, laparoscopic nephrectomy). Increased acceptance of renal embolization will require better embolic agents with improved ablation efficacy and better safety profiles. Comparing embolic agents requires understanding their mechanisms of action at the histologic level. In this issue of Radiology, Kónya et al (2) report the temporal histologic changes caused by a 1:1 ethiodized oil–ethanol mixture (EEM). Their goal was to better understand EEM’s mechanism of action and to clarify whether it improves embolization efficacy.
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The authors studied the temporal sequence of histopathologic changes after renal embolization with a 1:1 EEM to elucidate the mechanism of action. In five rabbits, the right kidney was embolized with the EEM until capillary stasis was reached. The rabbits were sacrificed at varying time intervals to a maximum of 14 days after the procedure. The left kidney was embolized immediately before sacrifice so that the authors could look at acute changes. In all kidneys, absolute ethanol was injected after the EEM to promote thrombosis of the main renal artery.
Complete arterial stasis was achieved immediately in all kidneys. Tiny droplets of EEM were seen in the renal veins of six of 10 kidneys, indicating that the EEM was passing through the capillary level. In the first few hours, the histologic changes consisted of endothelial sloughing, fibrin thrombus formation, and precipitation of proteins within arteries down to the level of the arcuate arteries. By 24 hours, the kidneys were completely infarcted. Progressive liquefaction and inflammatory cell infiltration were seen on days 5–7. The authors saw no radiographic or pathologic evidence of ethiodized oil in the lungs.
The Practice
Clinical use.—Even with current methods, renal embolization has a role in definitive therapy (in patients who cannot tolerate surgery), as well as in adjunctive presurgical therapy. In a recent study, preoperative embolization provided a survival benefit (3). Patients with renal cell carcinoma who underwent embolization plus resection had 5- and 10-year survival rates of 62% and 47%, respectively, compared with rates of 35% and 23% for those treated with nephrectomy alone. More effective embolic agents could make embolization an even more attractive therapy.
While we may think that liquid agents like ethanol penetrate out to the capillaries, results of histologic studies demonstrate otherwise. Ethanol-induced spasm, protein coagulation, and red blood cell clumping occlude branch arteries before the ethanol can reach the smallest arterial branches. This probably accounts for the sparing of cortical tissue seen in some studies. Results of histologic studies have also shown that the degree of ethanol dilution, the type of diluent used, and even the rate of injection affect the level of arterial occlusion, the potential for recanalization, and the type and extent of tissue necrosis.
The results of the study by Kónya et al show us that a 1:1 EEM does not cause immediate spasm or arterial wall damage, thus allowing the EEM to penetrate all the way through the capillaries. Combination therapy with main renal artery ethanol embolization prevented the EEM from completely washing through to the venous side (only tiny droplets passed through). Since the EEM distributes more completely throughout the entire arteriocapillary distribution, one would expect more complete tissue ablation to occur with this agent than with ethanol alone. This was nicely shown by the total necrosis seen histologically.
Future opportunities and challenges.—While the results of the current study are encouraging, there are several challenges yet to be addressed. The technique reported is a two-stage procedure in which ethanol is used after the EEM injection. It would be preferable to use a single agent that would penetrate to the capillaries and effectively occlude the main artery. This would simplify the procedure. Using pure ethanol negates the benefits of increased visibility and better injection control provided by the use of the EEM, especially since the ethanol is used after the EEM. At that point, arterial flow will be reduced, increasing the risk of reflux and nontarget embolization.
It is also necessary to study whether EEM is as efficacious in tumors. Tumor vascularity differs from normal renal vascularity in several aspects. Malignancies have arteriovenous shunts that may divert some of the EEM before it reaches the periphery of the tumor. Also, parasitized arteries may supply blood to the periphery of the tumor and maintain viability despite renal artery occlusion. This problem is suggested by the results of a study (4) of angiomyolipoma embolization. Lee et al used a 1:3 EEM in 21 tumors (15 patients). Eight tumors failed to decrease in size, and several re-bled, indicating that the tumors had not been completely devascularized. However, unlike the EEM used in the study of Kónya et al, the EEM used by Lee et al was a more diluted ethiodized oil mixture (25%) and was not supplemented with any other agent to occlude the main inflow arteries.
Summary
Results of histologic analysis show that a 1:1 EEM has an action that is distinct from that of ethanol, and when EEM embolization is coupled with main renal artery occlusion, it results in more complete renal infarction. Further studies are needed to determine if these results can be translated into improved renal cancer therapy.
REFERENCES
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