By Steven C Rose
The evidence supporting the use of transarterial chemoembolization (TACE) and Yttrium-90 transarterial radioembolization (TARE) to treat primary and secondary liver malignancies for palliation, survival benefit, bridging or downstaging to liver transplant or hepatic resection is expanding, both with respect to volume and quality. As a result, the number of these procedures being performed is on the rise. However, unintended non target delivery of TACE or TARE agents into any of the various hepaticoentric arteries that course from an intrahepatic artery to implant into an extra hepatic organ such as the stomach or small intestine can result in serious complications, especially gastrointestinal ulcerations, particularly with Y-90 microspheres. In the 1990s, the reported rates of such ulcerations was in the range of 15%. Subsequently, with standard lobar or sublobar dose delivery, rigorous coil embolization of all identified hepaticoentric arteries, and liberal use of core beam CT, the reported rate of gastrointestinal ulceration from TARE generally reduced to the range of 2–5%. Thorough coil embolic protection is both technically challenging and time consuming, and occasionally cannot be accomplished. An unintended consequence of coil embolization of the gastroduodenal artery is the subsequent angiographic appearance of “new” hepaticoentric arteries such as the supraduodenal artery that occur in 35% of patients. These are difficult, and at times impossible to catheterise and to place microcoils in.
Recently several devices have been developed and used to prevent retrograde reflux of blood and embolic agents. Examples have included temporary balloon occlusion of the targeted hepatic artery and the use of Surefire Infusion System (Surefire Medical). In the porcine renal artery model, the device was demonstrated to be nearly 100% effective in preventing reflux of small tantalum microspheres.
An important concept is that once these devices are deployed, two distinct vascular compartments are created: 1) the vascular territory downstream or peripheral to the device tip (eg, the right hepatic artery supplying the right hepatic lobe), and 2) the remaining systemic arteries in the rest of the body. One unintended but beneficial effect of the occlusive or nearly occlusive nature of these devices is the significant reduction in blood pressure downstream from the antireflux device. With the deployment, it has been shown that the downstream reduction in blood pressure occurs universally, and is in the range of 15–20mmHg, mean. The haemodynamic result is that in all downstream hepaticoentric arteries, the blood flow is forced in a hepatopedal direction with a force of 15-20mmHg. This differential in blood pressure between the two vascular compartments has been termed the protective pressure gradient. The implication is that these devices provide both retrograde and antegrade protection. Potentially coil embolization will no longer be necessary to prevent non-target radioembolization. Additionally, by not coil embolizing the gastroduodenal arteries, the phenomenon of recruitment of supraduodenal arteries is avoided.
Morshedi and coworkers presented their analysis on practice impact of using coil only versus Surefire Infusion System only protection in a similar group of patients undergoing Y-90 TARE with resin microspheres. They found that compared to the coil only cohort, SIS alone protection resulted in a 90 minute reduction in procedure time, a 35 minute reduction in fluoroscopy time, a 34 % reduction in the volume of contrast media used for the planning mesenteric angiographic procedure, and a cost reduction of US$6,870 for both the planning and treatment procedures combined.
One important caveat regarding use of antireflux devices is noteworthy. Since by nature, these devices are one way valves, the usual end point for embolization, fluoroscopic monitoring of contrast media washout and the occurrence of stasis or substasis of blood flow is compromised. As a result, a real danger of over embolization is present. Rose and colleagues have reported on two cases of serious inadvertent overembolization that occurred with lobar TACE procedures. In both cases, the protective pressure gradient was reduced from a pre-TACE level of 20mmHg to a post-TACE level of 0–3mmHg mean, indicative of embolic oversaturation of the targeted vascular territory. As a result, they have modified their practice to measuring the protective pressure gradient intraprocedurally (PPG= blood pressure measured in a 6Fr femoral artery sheath minus the blood pressure measured through the infustion system microcatheter with the tip expanded) after each aliquot of approximately 10% of the TACE or Y-90 resin microsphere dose. If a significant reduction in protective pressure gradient occurs, usually in the range of 40-70%, the lobar TACE procedure was terminated. As a result, the lobar TACE procedure was halted prior to deliver the entire intended TACE dose in 60% of lobar TACE procedures, with a marked reduction in liver toxicity. It appears that intraprocedural interval blood pressure differential assessment is probably not warranted with Y-90 TARE or segmental TACE procedures.
In summary, temporary anti-reflux devices are available that appear to provide both adequate retrograde and antegrade protection against nontarget delivery of cytotoxic agents. It seems that these devices are an attractive cost-effective alternative to permanent coil embolization of hepaticoentric arteries. These devices can also be used to exceed stasis, which may be beneficial in increasing tumour uptake in segmental or super-selective procedures. In lobar TACE procedures, there is a risk of excessive embolic saturation and liver toxicity, and this risk can be mitigated by intraprocedural interval measurement of protective pressure gradient.
Steven C Rose is professor of Clinical Radiology and section chief, Interventional Oncology, University of California, San Diego Health Sciences, California, USA. He is a proctor and minor stockholder in Sirtex Medical, a minor stockholder in Nordion, on the Medical Advisory Board of both AngioDynamics and BTG. He is a consultant to Surefire Medical, XLSci Tech and Embolox, and a speaker for Guerbet