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Published online before print December 10, 2004, 10.1148/radiol.2342031996
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(Radiology 2005;234:625-630.)
© RSNA, 2004

Vascular and Interventional Radiology

Preoperative Percutaneous Portal Vein Embolization: Evaluation of Adverse Events in 188 Patients1

Donatella R. Di Stefano, MD, Thierry de Baere, MD, Alban Denys, MD, Antoine Hakime, MD, Gilles Gorin, MD, Michel Gillet, MD, Jean Saric, MD, Hervé Trillaud, MD, Philippe Petit, MD, Jean-Michel Bartoli, MD, Dominique Elias, MD and Jean-Robert Delpero, MD

1 From the Institut Paoli Calmettes, Marseille, France (D.R.D.S., J.R.D.); Department of Interventional Radiology, Institut Gustave Roussy, 39 Rue Camilles Desmoulins, 94805 Villejuif, France (T.d.B., A.H., D.E.); Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland (A.D., M.G.); Hôpital Saint André, Bordeaux, France (G.G., J.S., H.T.); and Centre Hospitalier Universitaire La Timone, Marseille, France (P.P., J.M.B.). Received December 9, 2003; revision requested February 16, 2004; revision received April 5; accepted April 22. Address correspondence to T.d.B. (e-mail: debaere@igr.fr).


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 MATERIALS AND METHODS
RESULTS
DISCUSSION
 REFERENCES
 
PURPOSE: To retrospectively assess the frequency of adverse events related to percutaneous preoperative portal vein embolization (PPVE).

MATERIALS AND METHODS: Institutional review board did not require its approval or patient informed consent for this study. The adverse events that occurred during PPVE or until planned hepatic surgery was performed or cancelled were retrospectively obtained from clinical, imaging, and laboratory data files in 188 patients (109 male and 79 female patients; mean age, 60 years; range, 16–78 years). Liver resection was planned for metastases (n = 137), hepatocarcinoma (n = 31), cholangiocarcinoma (n = 15), fibrolamellar hepatoma (n = 1), and benign disease (n = 4). PPVE was performed with a single-lumen 5-F catheter and a contralateral approach with n-butyl cyanoacrylate mixed with iodized oil as the main embolic agent. The rate of complications in patients with cirrhosis was compared with that in patients without cirrhosis by using the {chi}2 test.

RESULTS: Adverse events occurred in 24 (12.8%) of 188 patients, including 12 complications and 12 incidental imaging findings. Complications included thrombosis of the portal vein feeding the future remnant liver (n = 1); migration of emboli in the portal vein feeding the future remnant liver, which necessitated angioplasty (n = 2); hemoperitoneum (n = 1); rupture of a metastasis in the gallbladder (n = 1); transitory hemobilia (n = 1); and transient liver failure (n = 6). Incidental findings were migration of small emboli in nontargeted portal branches (n = 10) and subcapsular hematoma (n = 2). Among the 187 patients in whom PPVE was technically successful, there was a significant difference (P < .001) between the occurrence of liver failure after PPVE in patients with cirrhosis (five of 30) and those without (one of 157). Sixteen liver resections were cancelled due to cancer progression (n = 12), insufficient hypertrophy of the nonembolized liver (n = 3), and complete portal thrombosis (n = 1).

CONCLUSION: PPVE is a safe adjuvant technique for hypertrophy of the initially insufficient liver reserve. Post-PPVE transient liver failure is more common in patients with cirrhosis than in those without cirrhosis.

© RSNA, 2004


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
 REFERENCES
 
Preoperative portal vein embolization (PPVE) was described in 1986 in Japan (1). During the early 1990’s, only a few PPVE studies were performed, and they were conducted in Japan and France (2–4). Today, PPVE is increasingly used for preoperative treatment of patients scheduled to undergo liver resection when the volume of the future remnant liver appears to be insufficient. If PPVE is not performed, these patients would be exposed to a major risk of postoperative hepatic failure. Most surgical teams believe that the minimal volume of the future remnant liver required for a normal liver is at least 25% of that of the initial functional liver (5) and that this percentage should be substantially greater in patients with chronic liver disease (6) or those who have previously undergone chemotherapy (7,8). PPVE of the portal vein branch that feeds the liver segment and is to be resected enables the redistribution of portal blood flow to the branches of the future remnant liver. This portal blood flow, which is rich in hepatotropic substances—namely insulin and glucagon (9)—induces hypertrophy of the nonembolized segments of the future remnant liver, thereby allowing the planned resection to be performed.

To our knowledge, only one study (10) has focused on adverse events related to PPVE. Thus, the purpose of our study was to retrospectively assess the frequency of adverse events related to PPVE.


   MATERIALS AND METHODS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
DISCUSSION
 REFERENCES
 
Patients
The institutional review boards in all centers participating in the study did not require their approval or patient informed consent. Between January 1990 and March 2001, 188 patients (109 male and 79 female patients; mean age, 60 years; range, 16–78 years) were scheduled to undergo PPVE. PPVE was to be performed before liver resection for metastases of colorectal origin in 137 patients, hepatocarcinoma in 31 patients, cholangiocarcinoma in 15 patients, fibrolamellar hepatoma in one patient, and benign disease in four patients (including two with focal nodular hyperplasia and two with adenomas). Thirty patients had underlying Child A cirrhosis. PPVE was always performed to increase the volume of an initially insufficient future remnant liver and never as anticancer therapy, as reported elsewhere (1). PPVE was indicated when the ratio between the volume of future remnant liver to the volume of the total functional liver was less than 25% in patients without underlying cirrhosis and normal findings with the indocyanine green test and when this ratio was less than 40% in the others. The planned liver resection procedures were as follows: right hepatectomy in 89 patients, right hepatectomy extended to segment IV in 83, atypical anatomic resection in 11, and segmentectomy associated with wedge resection in five.

PPVE Procedure
Ninety-five procedures were performed in one center by three operators (including T.d.B.), 35 procedures were performed in two centers by one operator (A.D.), and 58 procedures were performed in two centers by two operators (J.M.B., H.T,), including 29 procedures in each center by each operator. All operators were interventional radiologists with a minimum of 3 years of experience in vascular interventional procedures; the initial experience in PPVE of each operator is included in the study. PPVE was performed with use of conscious sedation or general anesthesia, and the portal vein was accessed by means of ultrasonography (US)-guided percutaneous puncture of a portal branch of the future remnant liver with a 5-F needle catheter, as described elsewhere (4). Because most of the anticipated surgical procedures were a right hepatectomy or an extended right hepatectomy, a peripheral portal branch of segment III or the Rex recess was punctured most frequently by means of a subxiphoid route. After placement of the catheter tip in the main portal trunk, digital subtraction portography was performed to identify individual branches and anatomic variations (Fig 1). After selective catheterization, the targeted segmental portal veins were embolized one after the other by using the flow-guided technique and constant fluoroscopic surveillance. A mixture of 1 mL of n-butyl cyanoacrylate (NBCA) (Histoacryl-Blue; Braun, Melsungen, Germany) with 1–3 mL of iodized oil (Lipiodol; André Guerbet, Aulnay-sous-Bois, France) was the main embolic agent used in all but our first four patients, in whom gelatin sponges (Gelfoam) were used. Details of the embolization technique are reported elsewhere (2–4). Twenty patients received embolization particles in addition to NBCA because of technically challenging branches. The end point of the procedure was complete occlusion of the targeted portal branches, as assessed with direct portography. Then, the 5-F catheter was retrieved without embolization of the transhepatic puncture track.



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  		Figure 1a. Images obtained in 64-year-old man with a large right liver metastasis discovered 2 years after resection of primary colorectal cancer. (a) Transverse CT scan obtained before PPVE shows large liver metastasis (arrow) in right lobe and small left lobe (arrowhead), the volume of which was estimated to be 30% of total liver volume. (b) Frontal portogram obtained before embolization shows patent portal vein and its intrahepatic branches. (c) Frontal portogram obtained after embolization of right portal vein shows redistribution of portal flow toward future remnant liver. (d) Transverse CT scan obtained 4 weeks after PPVE shows future remnant liver, which accounted for 56% of complete liver volume.

 


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  		Figure 1b. Images obtained in 64-year-old man with a large right liver metastasis discovered 2 years after resection of primary colorectal cancer. (a) Transverse CT scan obtained before PPVE shows large liver metastasis (arrow) in right lobe and small left lobe (arrowhead), the volume of which was estimated to be 30% of total liver volume. (b) Frontal portogram obtained before embolization shows patent portal vein and its intrahepatic branches. (c) Frontal portogram obtained after embolization of right portal vein shows redistribution of portal flow toward future remnant liver. (d) Transverse CT scan obtained 4 weeks after PPVE shows future remnant liver, which accounted for 56% of complete liver volume.

 


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  		Figure 1c. Images obtained in 64-year-old man with a large right liver metastasis discovered 2 years after resection of primary colorectal cancer. (a) Transverse CT scan obtained before PPVE shows large liver metastasis (arrow) in right lobe and small left lobe (arrowhead), the volume of which was estimated to be 30% of total liver volume. (b) Frontal portogram obtained before embolization shows patent portal vein and its intrahepatic branches. (c) Frontal portogram obtained after embolization of right portal vein shows redistribution of portal flow toward future remnant liver. (d) Transverse CT scan obtained 4 weeks after PPVE shows future remnant liver, which accounted for 56% of complete liver volume.

 


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  		Figure 1d. Images obtained in 64-year-old man with a large right liver metastasis discovered 2 years after resection of primary colorectal cancer. (a) Transverse CT scan obtained before PPVE shows large liver metastasis (arrow) in right lobe and small left lobe (arrowhead), the volume of which was estimated to be 30% of total liver volume. (b) Frontal portogram obtained before embolization shows patent portal vein and its intrahepatic branches. (c) Frontal portogram obtained after embolization of right portal vein shows redistribution of portal flow toward future remnant liver. (d) Transverse CT scan obtained 4 weeks after PPVE shows future remnant liver, which accounted for 56% of complete liver volume.

 
Blood screening tests (analysis of aspartate aminotransferase, alanine aminotransferase, and bilirubin levels; prothrombin time; and complete blood cell count) were performed before PPVE and on every day during hospitalization after PPVE. A spiral computed tomographic (CT) scan obtained during the portal phase with 5-mm collimation was used to calculate the volume of the future remnant liver on the basis of manually contoured three-dimensional reconstruction, as described elsewhere (4). Volumetric calculations were performed by a senior radiologist (D.R.D.S., T.d.B., A.D., H.T.), in accordance with the hepatobiliary surgeon’s surgical plan, before the PPVE procedure and within a week before the anticipated liver surgery. Patients were scheduled to undergo surgery 4–6 weeks after PPVE.

Data Collection
Adverse events were abstracted from the procedure reports and the clinical, imaging, and laboratory data files, which were reviewed by at least one physician (T.d.B., D.R.D.S., A.D., H.T.) in each center. Adverse events that necessitated specific treatment or modification of the clinical status and that were enough to prolong the hospital stay were defined as complications. Adverse events that did not require treatment and that did not prolong the hospital stay (eg, an unexpected imaging abnormality without clinical consequences) were defined as incidental findings. All patients were followed up at least until the surgical procedure was performed or cancelled.

Statistical Analysis
The {chi}2 test was used to compare the occurrence of adverse events in patients with and patients without cirrhosis and to compare the rate of hypertrophy in patients with NBCA migration in the future remnant liver versus hypertrophy in patients without this post-PPVE image finding. Comparisons were performed with statistical software (Statview; SAS Institute, Cary, NC). A difference with a P value of less than .05 was considered statistically significant. Technical success was defined as insertion of the catheter in the portal vein and completion of embolization. Clinical success was defined as completion of the surgical procedure.


   RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
DISCUSSION
 REFERENCES
 
Technical and Clinical Success
Technical success was achieved in 187 of the 188 patients. The only failure occurred in a patient who developed complete portal thrombosis during the procedure. The mean delay between PPVE and surgery was 33 days in patients without cirrhosis and 39 days in patients with cirrhosis. Mean increases in liver volume of 62% and 41% were observed in the nonembolized future remnant liver in noncirrhotic and cirrhotic livers, respectively (Fig 1).

The clinical success rate was 86%, with surgery being performed in 162 of the 188 patients who had undergone PPVE. Surgery was cancelled because of tumor progression in 12 patients, complete portal thrombosis in one patient, and insufficient hypertrophy of the future remnant liver in three patients.

In the 12 patients with tumor progression, peritoneal carcinomatosis was discovered at surgery in four patients, extrahepatic metastases were detected before surgery in four, and an increase in the liver tumor volume was detected in four at CT performed for volumetry immediately before surgery (including an increase in the nonembolized liver in three patients and in the embolized liver in one patient).

Adverse Events
Of the 188 patients who underwent PPVE, 164 (87.2%) did not experience adverse events. Among the 24 patients (12.8%) with adverse events, 12 had complications that either prolonged the hospital stay or necessitated treatment and 12 had incidental imaging findings discovered at preoperative CT.

The 12 complications included complete portal thrombosis (n = 1), inadvertent NBCA migration in the main left portal vein feeding the future remnant liver (n = 2), hemoperitoneum (n = 1), hemobilia (n = 1), rupture of a metastasis into the gallbladder (n = 1), and transient liver failure (n = 6). Portal thrombosis was found at the end of the PPVE procedure in a patient with a replaced anterior right portal branch arising from the left portal vein (Fig 2). In addition, this patient had mild stenosis of the origin of the branch feeding liver segments II and III, which could have been due to previous liver metastasectomy. During the procedure, blood flow in the portal system was observed to slow down; this was followed by complete occlusion of the left portal vein, as evidenced on the final portogram. Migration of NBCA in the untargeted left portal branch was not depicted with fluoroscopic monitoring during the procedure or on the subsequent CT scan. Hepatectomy was cancelled, and the patient underwent liver transplantation.



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  		Figure 2a. Images obtained in 65-year-old man who had previously undergone metastasectomy for colon cancer. (a) Frontal portogram obtained toward end of PPVE shows large NBCA embolus (black arrow) at the origin of anterior branch of right portal vein. There is proximal narrowing (white arrow) of the left portal vein. (b) Transverse CT scan obtained 24 hours later shows thrombosis of the left portal branch (arrow) and NBCA in right portal branches (arrowheads).

 


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  		Figure 2b. Images obtained in 65-year-old man who had previously undergone metastasectomy for colon cancer. (a) Frontal portogram obtained toward end of PPVE shows large NBCA embolus (black arrow) at the origin of anterior branch of right portal vein. There is proximal narrowing (white arrow) of the left portal vein. (b) Transverse CT scan obtained 24 hours later shows thrombosis of the left portal branch (arrow) and NBCA in right portal branches (arrowheads).

 
The two instances of inadvertent migration of NBCA into the left portal branch that fed the future remnant liver occurred because the catheter had dislodged an NBCA fragment that was initially in an adequate location (Fig 3). These events occurred toward the end of the procedure, when the portal systems that fed the liver scheduled for surgery were nearly completely occluded. Immediately after these instances of migration, angioplasty of the left portal vein was performed to achieve recanalization and to shatter the undesired NBCA emboli. Despite an initially satisfactory angioplasty result, a portoportal graft was necessary in one patient during liver resection because of subsequent portal thrombosis. The other patient underwent the scheduled hepatectomy without any complications.



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  		Figure 3a. Images obtained in 55-year-old man with metastases from colorectal neoplasm. (a) Frontal portogram shows that right portal vein was occluded (white arrow). Fragment of NBCA partially occluded left portal trunk (black arrow). (b) Frontal portogram obtained after angioplasty of left portal vein demonstrates patency of left portal trunk (arrow). (c) Transverse CT scan obtained before hepatectomy shows voluminous fragment of NBCA in left portal vein (arrow). (d) CT scan obtained 1 year after right hepatectomy and creation of a portoportal graft demonstrates cavernous transformation (arrow) of portal vein.

 


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  		Figure 3b. Images obtained in 55-year-old man with metastases from colorectal neoplasm. (a) Frontal portogram shows that right portal vein was occluded (white arrow). Fragment of NBCA partially occluded left portal trunk (black arrow). (b) Frontal portogram obtained after angioplasty of left portal vein demonstrates patency of left portal trunk (arrow). (c) Transverse CT scan obtained before hepatectomy shows voluminous fragment of NBCA in left portal vein (arrow). (d) CT scan obtained 1 year after right hepatectomy and creation of a portoportal graft demonstrates cavernous transformation (arrow) of portal vein.

 


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  		Figure 3c. Images obtained in 55-year-old man with metastases from colorectal neoplasm. (a) Frontal portogram shows that right portal vein was occluded (white arrow). Fragment of NBCA partially occluded left portal trunk (black arrow). (b) Frontal portogram obtained after angioplasty of left portal vein demonstrates patency of left portal trunk (arrow). (c) Transverse CT scan obtained before hepatectomy shows voluminous fragment of NBCA in left portal vein (arrow). (d) CT scan obtained 1 year after right hepatectomy and creation of a portoportal graft demonstrates cavernous transformation (arrow) of portal vein.

 


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  		Figure 3d. Images obtained in 55-year-old man with metastases from colorectal neoplasm. (a) Frontal portogram shows that right portal vein was occluded (white arrow). Fragment of NBCA partially occluded left portal trunk (black arrow). (b) Frontal portogram obtained after angioplasty of left portal vein demonstrates patency of left portal trunk (arrow). (c) Transverse CT scan obtained before hepatectomy shows voluminous fragment of NBCA in left portal vein (arrow). (d) CT scan obtained 1 year after right hepatectomy and creation of a portoportal graft demonstrates cavernous transformation (arrow) of portal vein.

 
The hemoperitoneum was revealed 24 hours after PPVE due to abdominal pain and collapse. An emergency laparotomy with surgical drainage was required for treatment, and the exact cause of the bleeding remains unknown. This patient finally underwent hepatectomy, which had been postponed until 4 months after PPVE instead of the usual 4–6 weeks.

The case of transitory hemobilia was revealed because of hemorrhage through a biliary tube that had been inserted for drainage of a hilar bile duct carcinoma. Hemobilia resolved spontaneously without the need for a blood transfusion, and liver resection was performed as planned.

The rupture of a liver segment V metastasis into the gallbladder was revealed as a result of acute peritonitis 6 weeks after PPVE (Fig 4). Results of laparotomy helped confirm the rupture, and cholecystectomy and peritoneal drainage were then performed. The planned liver resection was performed 2 months later. This patient died of peritoneal carcinomatosis 8 months after liver resection.



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  		Figure 4a. Images obtained in 47-year-old man with metastases from rectal neoplasm in right lobe of liver. (a) Transverse CT scan obtained before embolization shows metastasis (arrowhead) located in gallbladder fossa. (b) Transverse CT scan obtained at admission for peritonitis shows gallbladder and metastasis merged in a tumoronecrotic mass (arrowhead).

 


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  		Figure 4b. Images obtained in 47-year-old man with metastases from rectal neoplasm in right lobe of liver. (a) Transverse CT scan obtained before embolization shows metastasis (arrowhead) located in gallbladder fossa. (b) Transverse CT scan obtained at admission for peritonitis shows gallbladder and metastasis merged in a tumoronecrotic mass (arrowhead).

 
Six cases of transient liver failure were diagnosed when self-resolving ascites occurred in three patients and when serum bilirubin levels increased to twice the baseline values in three patients, with transient jaundice in one patient. The occurrence of post-PPVE transient liver failure in the 187 patients who underwent PPVE was significantly (P < .001) increased in patients with cirrhosis versus those without cirrhosis, with five of these six liver failures occurring in patients with cirrhosis and one failure occurring in a patient without liver cirrhosis. All cases of transient liver failure resolved in fewer than 6 days, with no further modification of the Child status in these patients.

Incidental findings included two cases of subcapsular hematoma located at the puncture site and 10 cases of migration of small NBCA fragments in the future remnant liver (Fig 5). The incidental findings were all depicted at CT performed for the volumetric studies at 4–6 weeks after PPVE. These findings did not lead to a specific treatment or modification of the timing and completion of the initially planned liver resection. In 10 patients, one to three (mean, 1.4) small NBCA fragments were seen in distal portal branches at the periphery of the future remnant liver with CT. None of these patients had abnormal patterns of liver enhancement at CT, and there were no reports of any symptoms between PPVE and liver resection. In this subset of patients, hypertrophy induced in the future remnant liver after PPVE was not different from that observed in the other patients in the series, and no specific abnormality was depicted in the parenchyma of the future remnant liver during surgery.



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  		Figure 5. Transverse CT scan obtained after right portal vein embolization in a 72-year-old woman with metastases from colorectal cancer. Two small NBCA fragments (arrows) are visible in distal portal branch of the left lobe.

 

   DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES
 
PPVE is increasingly used to permit the resection of liver tumors in patients who are not considered candidates for surgery because the volume of the future remnant liver is deemed insufficient (3,7,11). PPVE has been shown to improve the tolerance and outcome of liver resection in patients with underlying liver disease (12). Because PPVE is not an independent procedure but an adjuvant to surgery, it should remain as minimally invasive as possible. On one hand, any major complication related to PPVE could compromise the future liver resection, which is nearly always the last resort for cure. On the other hand, when PPVE is performed, there is no guarantee that surgery will ultimately be performed because of the potential for tumor growth, the discovery of an occult tumor during laparotomy, or insufficient hypertrophy of the future remnant liver.

According to the PPVE methods described by different authors, the portal system can be accessed by using four different approaches. Most often, access to the portal system is achieved by using an ipsilateral approach—in which the liver parenchyma targeted for PPVE is traversed (11)—or a controlateral approach—in which the parenchyma of the future remnant liver is traversed (4,13). More recently, a transjugular route has been reported (14). Finally, the jejunal veins can be cannulated during surgery (15). Such an approach, however, should probably be performed only when the percutaneous route is impossible or contraindicated or when laparotomy is performed for another purpose. The transjugular approach can be proposed if it is impossible to perform the more standard percutaneous transhepatic ipsilateral or contralateral approach because the tumor is obstructing the access track or hemostasis is impaired (14). The contralateral approach was developed in France (4,13) and was the only approach used in our experience. Its advantages are the use of smaller catheters, easy catheterization without sharp angulation, and flow-guided distal embolization; in addition, the quality of the final portogram is good. The main drawback for the contralateral approach is that the future remnant liver is punctured and the catheter is inserted retrogradely through the vein of the future remnant liver, which may damage the parenchyma or the feeding veins. To minimize such injury, puncturing should be limited as much as possible and US guidance should be used to target a distal portal vein.

The only complication we observed that was probably directly related to the contralateral approach was complete portal vein thrombosis. We believe that the catheter maneuvers through a stenotic left branch feeding the future remnant liver were responsible for the thrombosis of this branch and, ultimately, complete portal vein thrombosis. This complication is one of the worst possible because hypertrophy cannot be achieved; thus, liver resection is out of the question. Such stenosis should be taken into account and preference may be given to the ipsilateral approach, in which only the portal branch of the liver segment awaiting resection is catheterized.

Disadvantages of the ipsilateral approach are complex catheterization maneuvers with use of a sidewinder catheter and coaxial microcatheters caused by the sharp angle between the branch that allows access and those targeted for embolization (16). Furthermore, larger catheters, usually 5.5 or 6 F, are used because a multiple-lumen catheter with an occlusion balloon is required (11). With the ipsilateral approach, it is often difficult to assess the effectiveness of PPVE with a final opacification of the portal system because PPVE is completed with embolization of the portal branch via which access has been achieved. Complications also arise when the ipsilateral route is used. Among those complications reported are septic necrosis due to arterial damage (8), migration of embolic material toward the future remnant liver (11), and complete portal thrombosis (16). Results of a recent study, however, did not find substantial differences between the complication rates of the ipsilateral and contralateral approaches (10). In theory, the use of an occlusion balloon associated with the ipsilateral approach should be the ideal solution to avoid any reflux in nontargeted veins. Nagino et al (11), however, reported two cases of migration of embolic material in nontargeted branches among 38 PPVE procedures in which a double- or triple-lumen catheter was used with an occlusion balloon.

Among the 12 cases of migration of NBCA into the future remnant liver, two were substantial; they occurred toward the end of the procedure when the right portal veins targeted for embolization were almost totally occluded. This emphasizes why particular attention should be paid when embolization is almost complete and when only one branch or a few branches with slow flow await occlusion. This is particularly true when veins in liver segment IV await occlusion and the right portal vein has already been occluded, in which case there is a risk of reflux in the left portal branch. In such a difficult situation, particulate embolization is probably easier to manage than NBCA to avoid reflux in the future remnant liver. Particulate embolization was performed in 20 patients in this series for segmental branches that were deemed too risky for embolization with NCBA. Cases of very mild NBCA migration were found in the future remnant liver in 10 (5%) of 188 procedures. These cases of migration did not compromise liver hypertrophy, probably because the very small NBCA fragments only occluded very distal branches. These cases of migration were probably related to NBCA fragments that were either jammed inside the catheter and released during flushing or attached to the outside wall of the catheter and shed when it was retrieved at the end of the procedure. To avoid emboli from NBCA jammed inside the catheter, embolization should be carefully monitored with fluoroscopy. In addition, the catheter tip should be maintained in the portal branches targeted for PPVE while it is abundantly flushed or during the first passage of the guidewire after injection of NBCA. The use of an introducer sheath with its tip located in a portal branch targeted for PPVE could help avoid the shedding of NBCA fragments attached to the outside wall of the catheter.

Hemorrhagic complications or adverse events such as hemoperitoneum, subcapsular hematoma, and transient hemobilia are related to the puncture. In addition to carefully seeking coagulation parameters, some authors recommend embolization of the puncture track when retrieving the catheter (13). Such a recommendation should be weighed carefully when using the contralateral approach because there is a risk of injecting embolic material in the portal system of the future remnant liver. Track coagulation with a device acting like a Bovie electrocautery instrument, namely radiofrequency systems (17), could be an option in the future and would also help avoid the hazards of potential inadvertent embolization.

The rupture of a metastasis in one of our patients is, to our knowledge, the first occurrence of such an event after PPVE. After PPVE, the growth rate of metastases has been reported to be faster in the liver without embolization than in that with embolization (18,19). PPVE, however, does not preclude tumor growth in the part of the liver in which embolization has been performed, and the natural history of cancer is probably a sufficient explanation for this rupture. This complication, however, underlines the fact that liver resection should be performed as soon as possible after PPVE. In the majority of our patients, 4 weeks was a reasonable period of time to allow sufficient hypertrophy of the future remnant liver without a major increase in tumor volume.

Modifications of liver blood test results and, more specifically, an increase in liver transaminase levels are common findings after PPVE (3,7,8,12). Liver insufficiency, however, and a bilirubin level more than twice the baseline value are not common findings. In our experience, these disturbances occurred in five of the 30 patients with cirrhosis and in one of the 157 patients without cirrhosis, a finding that demonstrates a significant difference between these two groups. Liver insufficiency always resolved spontaneously after a few days. All of our patients with cirrhosis had Child A disease, and this raised questions about the safety of PPVE in patients with Child B cirrhosis, owing to the need for adequate hepatic reserve and a regeneration capacity capable of sustaining the PPVE procedure and inducing hypertrophy (20–22).

Study limitations linked to the relative heterogeneity of practice because of the number of centers involved in this study are smoothed by the fact that all operators were first trained in the same center. Another limitation is the use of NBCA as the main embolic material. NBCA is not the most commonly used material, especially in the United States. Abdalla et al (5), in a review article, reported no statistically significant differences in the complication rates of different embolic materials.

We believe ours is the largest PPVE series reported, with a low complication rate even if the learning curve is included, in five centers. In this study, 6.4% of complications necessitated treatment or prolonged hospitalization, including 0.5% that precluded the scheduled liver resection. Therefore, PPVE can be considered a safe adjuvant to liver resection in more than 93.6% of cases. Although NCBA proved useful, it should probably be replaced by particulate material in difficult situations. Patients with cirrhosis develop more post-PPVE complications than do those without cirrhosis.


   ACKNOWLEDGMENTS
 
We acknowledge Lorna Saint Ange for editing and J. P. L’Homme and S. Ruffato for image management.


   FOOTNOTES
 
Abbreviations: NBCA = n-butyl cyanoacrylate, PPVE = preoperative portal vein embolization

Authors stated no financial relationship to disclose.

Author contributions: Guarantors of integrity of entire study, T.d.B., D.R.D.S.; study concepts, D.R.D.S., T.d.B., A.D.; study design, D.R.D.S., T.d.B.; literature research, D.R.D.S., T.d.B., A.H., D.E.; clinical studies, D.R.D.S., T.d.B., A.D., G.G., M.G., J.S., H.T., P.P., J.M.B., D.E., J.R.D.; data acquisition, D.R.D.S., T.d.B., A.D., H.T.; data analysis/interpretation, A.H., T.d.B.; statistical analysis, A.H., T.d.B., D.R.D.S., A.D., H.T.; manuscript preparation, D.R.D.S., T.d.B., A.H.; manuscript definition of intellectual content and revision/review, D.R.D.S., T.d.B.; manuscript editing, T.d.B., D.R.D.S., A.D., A.H.; manuscript final version approval, all authors


   REFERENCES
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
DISCUSSION
 REFERENCES
 

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