Jeff Geschwind, MD

Surgery is the treatment of choice for all primary and most metastatic liver tumors in patients without extrahepatic disease. One limitation to resection, however, is concern that the volume of liver parenchyma remaining after surgery (remnant liver) may not be sufficient to avoid lethal posthepatectomy liver failure.

In patients likely to have an insufficient volume of liver after surgery, preoperative portal vein embolization (PPVE) can be carried out on portal branches feeding the liver segment to be resected. This procedure redistributes portal blood flow to the branches of the liver that will remain and induces hypertrophy in unembolized segments. The planned hepatectomy can then proceed.

PPVE was first described in 1986 in Japan

 and again in studies from Japan and France in the early 1990s.

 The procedure is increasingly used today in the preoperative management of patients proposed for liver resection, who might otherwise be at major risk of postoperative hepatic failure.

Most surgical teams agree that the minimal volume of remnant liver should be at least 25% of the total normal liver volume

 and that this percentage should be further increased in cases of chronic liver disease

 Interindividual variability in volume liver segments is known to be high. The expected remnant liver portion should therefore undergo volumetric evaluation with 3D CT both before and four to five weeks after PPVE.

The portal system is accessed percutaneously under ultrasound guidance, through either an ipsilateral

 Access to the portal branches can also be obtained through cannulated jejunal veins or via a transjugular approach,

 though these strategies are far less common. The ipsilateral approach avoids puncturing healthy liver parenchyma that will remain following resection. Catheterization is more difficult with this approach, however, due to the sharp angle necessary. Use of a microcatheter

 or balloon occlusion catheters with three lumens may be required.

 It is also impossible to obtain a final portogram after embolization because the portal branch used for access is occluded during catheter retrieval.

The contralateral approach (Figure 1) allows anterograde catheterization with a gentle angle, and free-flow embolization is easier as well. The portal branch to be punctured must be upstream of any branch bifurcation requiring embolization. A final portogram can be obtained to evaluate the extent and completeness of embolization. The disadvantage of the contralateral approach is the necessity of traversing prospective remnant liver. Any damage to this section may preclude planned surgery.

A great variety of embolic materials can be used for PPVE. These include gelfoam, N-butyl cyanoacrylate, polyvinyl alcohol (PVA) particles, spheres, alcohol, fibrin glue, and coils.

 Embolization must be distal and long-lasting because surgery may not be performed until several weeks afterward.

Temporary embolic materials, such as gelfoam, or very proximal ones, such as coils, should probably be avoided. These materials appear to induce less hypertrophy than more pemanent embolic materials.

 Recanalization can occur in branches occluded with gelfoam

 or thrombin and fibrin adhesive mixtures.

 Proximal embolization with coils allows intraparenchymatous shunts to reopen.

Tris-acryl microspheres provide more complete embolization than PVA particles and are thus better at inducing hypertrophy in the remnant liver.

 We found that cyanoacrylate produced better hypertrophy than any other embolic material, having a 90% plus/minus 52% volume increase after 30 days (Figure 1) versus 53% plus/minus 6% after 43 days with gelfoam. Cyanoacrylate is one of the most aggressive embolic materials-distal, permanent, and capable of inducing an exothermic reaction when injected. It induced a highly intense inflammatory reaction in all specimens of resected liver during hepatectomy post-PPVE, fibrosis in 69% of the specimens, and small foci of necrosis in 17% (Figure 2).

Cellular disjunctions and inflammation are believed to promote the production of hepatic growth factor by fat-storing liver cells, which in turn should trigger hepatocyte regeneration. Growth of activated cells is also thought to be best if these cells are in the unembolized liver and supplied by portal blood containing hepatotrophic substances.

A period of four to five weeks is usually necessary and sufficient for patients to attain a high enough proportion of remnant liver within the total liver volume to permit surgery. We found that such hypertrophy was obtained in 117 out of 122 patients embolized with cyanoacrylate.

Surgery was performed on 111 of the 122 patients who had undergone PPVE, resulting in a 3% postoperative death rate. Cancellation of surgery was due to tumor progression or preoperative findings, such as peritoneal carcinomatosis, metastatic lymph nodes, or unsuspected liver metastases. The survival rate did not differ significantly between patients prepared by PPVE for hepatic resection and patients who underwent hepatectomy without prior embolization. We found the five-year survival rates to be 34% and 37%, respectively.

 Another French center recorded five-year survival rates of 40% and 38% for these two patient groups.

PPVE is usually well tolerated, requiring one or two days' stay in the hospital.

 Transient liver insufficiency, with a bilirubin level more than twice the baseline value, occurred significantly more often in cirrhotic (Child A) patients (five out of 30) than in noncirrhotic patients (one out of 157).

 Modified data from four French centers revealed a 6% complication rate in 188 procedures, though only 1% of the patients who underwent PPVE were then excluded from liver surgery.

Limitations to PPVE include cirrhosis, diabetes, and residual tumor in the remnant liver portion between embolization and surgery. Growth of the remnant liver is much smaller in patients with cirrhosis. Studies suggest that PPVE will cause the remnant volume to increase by 30% to 37% in such cases.

 Expansion of remnant liver is also reportedly lower in diabetic patients, due to the lack of insulin in the portal flow.

We found that tumor remaining in the unembolized liver after PPVE (i.e., tumor scheduled for wedge resection or radiofrequency ablation combined with hepatectomy) grew between one and 15.6 times faster than the unembolized liver parenchyma itself.

 It is difficult to know whether PPVE increases tumor growth rates in unembolized liver, or if this growth is due to the tumor's natural history. Clinicians should nonetheless aim to destroy tumor in the remnant liver portion at the time of PPVE to avoid further tumor growth that might preclude surgery. PPVE combined with RF ablation (Figure 3) is a useful means of attaining this goal. Both procedures can be performed safely and efficiently at the same time.

PPVE can also be combined with other interventional radiology techniques. For example, PPVE provided 101% hypertrophy of the volume of the unembolized liver in patients who had previously received intra-arterial chemotherapy through implanted ports.

 The hepatic artery in the territory scheduled for PPVE should be checked to ensure it is patent following transarterial chemoembolization (Figure 3). Failure to do so could lead to complete necrosis of the liver segment with occlusion of both the arterial and portal feeders.

In conclusion, PPVE widens the possibilities of curative resections in liver cancer patients. Survival rates are equivalent to those obtained after standard surgical resection, despite the fact that patients scheduled for PPVE usually have more severe disease.

The increased efficacy of new intravenous and intra-arterial chemotherapy regimens, associated with progress in surgical techniques, will extend the number of complicated hepatectomies and thus the need for PPVE. The procedure is primarily reported in the current literature for preparing the liver for hepatectomies resecting one side of the liver (right or left). In the future, it will be used increasingly before atypical and complex liver resections.

DR. DE BAERE is head of interventional radiology at the Institut Gustave Roussy in Villejuif, France, and DR. GESCHWIND is chief of interventional radiology at Johns Hopkins Hospital in Baltimore, U.S.

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Jeff Geschwind, MD

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