David Li • Richard H. Marshall • David C. Madoff
The hepatitis C epidemic in the United States has contributed to a dramatic rise of hepatocellular carcinoma (HCC), with HCC increasing in incidence at a rate of 4.5% per year from 1980 to 2005.1,2 HCC has a poor prognosis and is the third leading cause of cancer-related mortality despite being the sixth most common cancer worldwide.3 Given both its increased incidence and poor prognosis, the mortality rate from primary liver cancer has increased more than any other major cancer in the United States over the past several decades.1 In addition, the liver remains a common site of metastases from colorectal carcinoma and other primary tumors.4 Surgical resection of primary tumors and metastases confined to the liver remains the mainstay of curative therapy.5,6
In recent years, advances in hepatobiliary surgical techniques have led to improved morbidity and mortality in patients after hepatic resection.7,8 Despite these advances, major hepatic resection (i.e., greater than three Couinaud segments) places patients at risk for developing complications related to liver insufficiency in the perioperative period. The anticipated volume of liver which remains after surgery, termed the future liver remnant (FLR), has been shown to be a strong, independent predictor of postoperative complications.9,10
Portal vein embolization (PVE) is a well-established procedure to redirect portal blood flow to the intended FLR for patients who are candidates for extensive liver resection to promote hypertrophy of nonembolized segments that will remain after resection.11–13 When needed, this increased FLR volume is associated with improved biliary excretion, albumin uptake, and postoperative liver function in patients undergoing major hepatectomy.14–16 PVE has also been shown to improve the functional reserve of the FLR before surgery; reduce perioperative morbidity; and allow for safe, potentially curative hepatectomy in patients previously considered ineligible for resection based on anticipated small remnant liver volumes.17–20 This chapter summarizes the mechanism of action, current indications, outcomes, techniques, and complications related to PVE.
MECHANISM OF ACTION
The liver is unique for its enormous capacity for regeneration: even a loss of as much as two-thirds of the liver parenchyma can be compensated with complete recovery of liver function within 2 weeks.21Regeneration of the liver depends on portal blood flow delivering multiple mitogenic factors, the most potent hepatotrophic agents being hepatocyte growth factor (HGF) and tumor growth factor alpha (TGF-α).22,23 Comitogenic factors, such as insulin and glucagon, are transported via the portal system and act in concert with hepatotrophic agents to stimulate cytokine release and ultimately hepatocyte proliferation. The synergistic action of insulin with HGF accounts for the observation that hepatic regeneration rates are slower in diabetic as compared to nondiabetic patients.24,25
Regeneration of the liver depends on both the stimulus of injury and the condition of the liver parenchyma. Hepatocyte proliferation is directly proportional to the degree of severity of the insult to the liver: minor injuries (i.e., <10% parenchymal involvement) induce only localized mitotic reactions, whereas major injuries (i.e., >50% parenchymal involvement) induce multiple mitotic waves throughout the entire liver.21 Liver regeneration rates depend on the time from injury, with the greatest rate of regeneration after PVE occurring within the first 2 weeks (Fig. 31.1).10 Hepatocyte removal or necrosis is a stronger stimulus for liver regeneration as compared to cell-mediated apoptosis.26,27 Apoptosis is the predominant mechanism of cell death in PVE, thus regeneration after PVE occurs at a slower rate compared with hepatectomy.10 In addition, PVE is known to cause minimal pain and fever as compared to the postembolization syndrome associated with transarterial embolization where necrosis is the primary mechanism of cell death.28 Cirrhotic livers are known to have both a reduced rate and capacity for liver regeneration.29 Both a suboptimal hepatocyte microenvironment with fibrosis reducing delivery of portal flow and a blunted response of the diseased hepatocytes to hepatotrophic factors are thought to contribute to the reduced regeneration ability of cirrhotics.30 One novel approach to augmentation of liver regeneration rates in the setting of PVE has been the use of stem cells. Esch et al.31 reported greater absolute and relative FLR volumes after adjuvant stem cell infusion in conjunction with PVE in a small cohort of patients.
FUTURE LIVER REMNANT DETERMINATION
PVE is indicated when the anticipated FLR is insufficient to support hepatic function, particularly in the perioperative period, before the liver has had time to regenerate. Accurate calculation of the FLR is essential in triaging the potential hepatectomy candidates for whom PVE is indicated. Liver volume is directly correlated with a patient’s size; hence, normalizing the anticipated liver volume to a patient’s size results in a more accurate assessment of the FLR.32,33 This principle led to the proposal and clinical validation of a standardized FLR (sFLR) by Vauthey et al.,33 expressed as a ratio of the FLR over the total estimated functioning liver volume (TELV): sFLR = FLR/TELV.
Computed tomography (CT) volumetry serves as the standard for FLR measurement as it is accurate within ±5% of estimating normal liver parenchymal volumes (Fig. 31.2).33,34 Several methods have been used to measure TELV, including those based on CT volumetry, body surface area (BSA), or body weight. Vauthey et al. derived the following formula for estimating TELV by analyzing liver size and BSA in 292 Western adults: TELV = −794.41 + 1,267.28 × BSA, which has been demonstrated to be the least biased and most accurate in adult patients by meta-analysis as compared to similar formulas.35,36 Other formulas for determining TELV from CT volumetry are both tedious and imprecise because measurements of the tumor volume must be performed and excluded from the overall liver volume using this method. Ribero et al.37 verified that CT volumetry was less accurate than BSA for calculating sFLR by identifying a subset of patients for whom CT volumetry underestimated the risk of hepatic insufficiency. Chun et al.38 found the body weight method to be equally as predictive as BSA; however, a more recent study comparing direct volumetric liver measurement and estimated liver volume based on BSA found the TELV method to be superior (P < .005).39
Outcomes in Healthy Livers
Multiple studies have demonstrated that hepatectomy in a setting of sFLR less than 20% is associated with increased postoperative complications.10,13,40 As a result, the National Comprehensive Cancer Network treatment guidelines from 2013 (category IIA) endorse an sFLR of greater than 20% as a minimum threshold for patients without underlying liver disease to safely undergo hepatectomy, with consideration for PVE to be performed on patients below that threshold.5 Ribero et al.10 found that both sFLR less than 20% and degree of sFLR hypertrophy after PVE less than 5% predicted outcome after resection in a series of 112 patients (Fig. 31.3). Kishi et al.40 published a series of 301 consecutive patients who underwent extended right hepatectomy and found that patients with a preoperative sFLR less than 20% had significantly higher rates of postoperative liver insufficiency and death from liver failure compared with patients with sFLR greater than 20% (P < .05). In addition, patients who underwent PVE before surgery to increase their sFLR from less than 20% to greater than 20% had statistically equivalent rates of liver insufficiency as patients with greater than 20% at baseline (Fig. 31.4). This study confirmed both the sFLR threshold of less than 20% being associated with increased perioperative complications and the beneficial role of PVE in reducing perioperative complication rates in those patients who hypertrophy their liver to an sFLR greater than 20%.
Recently, Shindoh et al.41 have proposed the kinetic growth rate (defined as degree of hypertrophy at initial volume assessment divided by number of weeks elapsed after PVE) as a predictor of postoperative complications after hepatectomy as compared to the sFLR. They analyzed a series of 107 patients who underwent right PVE and subsequent right hemihepatectomy or extended right hepatectomy and found the kinetic growth rate to be the most accurate predictor of postoperative hepatic insufficiency and mortality when compared to sFLR or degree of hypertrophy measurements using receiver operating characteristic analysis (Fig. 31.5). Of the three measures, a kinetic growth rate cutoff value of less than 2.0% per week demonstrated the highest accuracy (81%), with sensitivity of 100% and specificity of 71% in predicting postoperative hepatic insufficiency.
Outcomes in Diseased Livers
Liver regeneration occurs at a reduced rate and capacity in diseased livers.21,29,30,42 This observation has directly correlated to clinical outcomes. De Meijer et al.43 performed a meta-analysis of four studies involving 1,000 patients and found that patients with greater than 30% steatosis of the liver had significantly higher risk of postoperative complications and postoperative death compared with patients without steatosis (relative risk and 95% confidence interval 2.01 and 1.66 to 2.44 vs. 2.79 and 1.19 to 6.51). Similarly, several series evaluating outcomes after extensive hepatic resection demonstrated higher rates of both postoperative hepatic insufficiency and mortality in cirrhotic patients.44,45 Hence, higher sFLR cutoffs are considered for patients with additional risk factors such as hepatic steatosis, hepatotoxic chemotherapy exposure, and compensated cirrhosis.
For patients with well-compensated cirrhosis (i.e., Child- Pugh class A) who are considered for resection, an sFLR greater than 40% is recommended. In support of this recommendation, Shirabe et al.46demonstrated that all cases (n = 7) of postoperative hepatic insufficiency occurred when the FLR was calculated to be less than 250 mL/m2 (which corresponds to a calculated sFLR of <40%) in a series of 80 cirrhotic patients who underwent major hepatic resection. A prospective alternative allocation trial in which 28 patients with chronic liver disease were allocated to PVE or no PVE before resection further validated the higher minimum sFLR cutoff of less than 40%; the PVE group had a mean sFLR size of 35% and demonstrated significantly lower incidence of complications including liver failure.47
Accelerated tumor growth after PVE has been reported for both primary and metastatic liver tumors.48–51 Progression of disease after PVE may preclude curative intent surgery; a 20% dropout rate after first-stage resection due to progression of disease has already been reported in two-stage hepatectomy series.52,53 Neoadjuvant chemotherapy can be administered in an attempt to provide tumor control in the interim between PVE and resection; however, concerns have been raised about its potential deleterious effect on liver function, liver hypertrophy, and lack of efficacy in preventing progression of disease.
Two separate series, one by Pawlik et al.54 and another by Vauthey et al.,55 have demonstrated an association of oxaliplatin with sinusoidal dilation and irinotecan with steatohepatitis. In the series by Vauthey et al.,55 the presence of steatohepatitis in patients who had undergone resection was correlated to increased 90-day mortality (14.7% vs. 1.6%; P = .001; odds ratio [OR] = 10.5; 95% CI, 2.0 to 36.4). Given these findings, Shindoh et al.56performed a retrospective analysis on a series of 194 patients with colorectal liver metastasis to determine the optimal FLR for patients treated with neoadjuvant chemotherapy. The authors found that both long duration of chemotherapy (defined as >12 weeks) and sFLR less than or equal to 30% were predictors of hepatic insufficiency (OR = 5.4, P = .004; OR 6.3, P = .019, respectively) (Fig. 31.6). No cases of postoperative mortality and only two cases of postoperative hepatic insufficiency were reported if the sFLR is greater than 30%, indicating that an sFLR greater than 30% may be a more appropriate cutoff value in patients who have received neoadjuvant chemotherapy, particularly if the duration of treatment is more than 12 weeks.
In addition, the effect of systemic neoadjuvant chemotherapy on liver hypertrophy after PVE has been addressed by several studies. Zorzi et al.57 reviewed FLR hypertrophy after PVE in patients with colorectal liver metastases who underwent PVE either with concomitant neoadjuvant chemotherapy (n = 43) or without chemotherapy (n = 22) before resection. The chemotherapy group, which included 26 patients treated in part with the vascular endothelial growth factor (VEGF) receptor blocker bevacizumab, demonstrated similar rates of hypertrophy when compared to the no chemotherapy group at 4 weeks after PVE. Similarly, Covey et al.58 also reported on patients with colorectal liver metastases who underwent PVE either with (n = 47) or without (n = 53) neoadjuvant chemotherapy. Both groups showed no significant difference in median contralateral liver growth after PVE. However, in a small series of 15 consecutive patients by Beal et al.,59 the volume increase of the anticipated FLR was reduced in the setting of chemotherapy (median of 89 vs. 135 mL, range of 7 to 149 vs. 110 to 254 mL; P = .016).
Chemotherapy has not been proven to prevent progression of disease between PVE and resection. A recent study examined the effect of chemotherapy on disease progression between the first and second stages of a two-stage hepatectomy.60 Of the initial 47 patients who underwent first-stage resection, 25 patients (53.2%) were treated with subsequent chemotherapy compared to 22 (46.8%) patients who did not receive interval chemotherapy. Eleven patients (23.4%) failed to complete second-stage hepatectomy due to progression of disease. There was no statistically significant difference in the number of patients with progression of disease between the groups treated or not treated with interval chemotherapy (n = 12 vs. n = 13; P = .561). The authors concluded that chemotherapy after stage 1 resection does not guarantee lower progression of disease rates, within the limitation that the study groups were not randomized.
TWO-STAGE HEPATECTOMY AND OUTCOMES OF EMBOLIZATION VERSUS LIGATION OF THE PORTAL VEIN
Two-stage hepatectomy has been developed to increase the number of patients with bilobar colorectal liver metastasis amenable for resection.61 During the first-stage treatment, tumor within the projected FLR is resected or, in some cases, ablated. Once the FLR is cleared of tumor, portal blood flow is directed toward the FLR either by portal vein ligation (PVL) or PVE of the ipsilateral tumor-bearing liver. Once adequate FLR hypertrophy is achieved, the second-stage hepatectomy targets the remainder of liver metastases, typically requiring a right or extended right hepatectomy. Brouquet et al.52 studied the outcomes of 65 patients with colorectal metastases who underwent first-stage hepatectomy, 47 of whom completed the second-stage resection in comparison to nonsurgical patients. Both study groups had disease confined to the liver and demonstrated an objective response to systemic chemotherapy. The overall 5-year survival rate of the surgical group was 51% compared to 15% for the medical group (P = .005). For the 47 patients who completed the second-stage resection, 5-year survival was improved to 64%. Hence, resection conferred a clear additional survival benefit.
As an alternative to PVE, intraoperative right PVL has been performed during the initial stage of two-stage hepatectomy or as a separate surgical intervention as a means of inducing FLR hypertrophy.62–64Results from comparative studies between PVE and PVL are mixed, with some studies demonstrating comparable liver hypertrophy, while others showing a liver hypertrophy benefit from PVE.
Both Aussilhou et al.65 (PVE: n = 18; PVL: n = 17) and Capussotti et al.66 (PVE: n = 31; PVL: n = 17) retrospectively compared patients who underwent PVE with patients who underwent PVL during the first stage of a two-stage hepatectomy and found comparable increases in left liver volume in the two groups. Other studies have found inferior FLR hypertrophy after PVL compared to PVE. Broering et al.67found that increase in left lateral liver volume was significantly higher for the PVE (n = 17) group compared to PVL (n = 17) (188 ± 81 mL vs. 123 ± 58 mL; P = .012) before extended right hepatectomy. In addition, hospital stay was significantly shorter for PVE compared to PVL (4 ± 2.9 days vs. 8.1 ± 5.1 days; P < .01). Robles et al.68 also compared left lobe hypertrophy in two-stage hepatectomy patients who underwent PVL (n = 23) versus PVE (n = 18). This group found that PVE resulted in improved median percentage increase of the FLR compared to PVL (40% vs. 30%, P < .05).68 The inferior hypertrophy after PVL may be explained by portal–portal shunts, which can lead to recanalization of the ligated right portal vein.69
PVE is as an adjunctive procedure to major hepatectomy. Hence, contraindications to PVE mirror those of hepatectomy. Severe portal hypertension precluding surgery is the only absolute contraindication to PVE. Also, in cases where tumor obstructs the portal system in the liver to be resected, PVE is not necessary as portal flow is already redirected to the FLR.70,71 Relative contraindications include uncorrectable coagulopathy, renal failure, and extrahepatic metastasis. Two-stage hepatectomy has expanded the patients with bilobar hepatic disease burden eligible for PVE and potential curative resection as will be further detailed in the following discussion; however, diffuse hepatic disease burden remains a contraindication to PVE.
Portal Venous Anatomy and Access Routes
Knowledge of standard portal vein anatomy and common variations is essential for both PVE and surgical planning.71 In standard anatomy, the splenic and superior mesenteric veins join to form the main portal vein, which divides into the left and right branches at the hepatic hilum. The right portal branch subdivides into anterior and posterior divisions, which supply Couinaud segments 5/8 and 6/7, respectively. The left portal branch subdivides into branches, which supply segments 4, 3, and 2. In one series of 200 patients studied with CT portography, standard anatomy (type I) was identified 65% of the time (Fig. 31.7).71,72 In the most common variation (type III), the right posterior portal vein is the first branch of the main portal vein, followed by bifurcation of the right anterior and left portal branches.
PVE has traditionally been performed via one of three approaches, termed transileocolic, contralateral, and ipsilateral techniques. The original approach, the transileocolic approach, is a surgical procedure where a right lower quadrant incision is used to access a major venous ileocolic branch via direct puncture, allowing for catheter manipulation to the portal vein. This approach has the advantage of avoiding puncture through the liver. However, the surgery has generally been replaced by the less invasive percutaneous contralateral and ipsilateral techniques, which are performed using ultrasound-guided transhepatic puncture.
The contralateral approach accesses the portal system via the FLR (Fig. 31.8A), preferably a peripheral branch of segment. The major advantage of the contralateral approach is easier catheter manipulation to the tumor-bearing liver because of fewer acute angles between access and target portal branches.12,73 In addition, embolization is performed with the catheter pointed toward the direction of flow. The major disadvantage of the contralateral approach is risk of damage to the FLR during access and catheter manipulation, which could potentially make a patient unresectable.
The ipsilateral approach accesses the portal system through the tumor-bearing liver, thus avoiding potential damage to the FLR during instrumentation (Fig. 31.8B). As demonstrated by Madoff et al.,74,75 the acute angles encountered between access and target portal branches during ipsilateral access can be overcome with the use of commercially available reverse curve catheters and microcatheters. In addition, catheterization of segment 4 is more straightforward via the ipsilateral approach should embolization of segment 4 be required (further detailed in the following text).
For the ipsilateral approach, access through the anterior segment of the right portal vein is associated with a lower complication rate and thus preferred.76 Care must be taken to avoid access through tumor to prevent peritoneal seeding. Figure 31.9 depicts a PVE performed via a transhepatic ipsilateral approach extending to segment 4 using trisacryl microspheres and coils in a patient with cholangiocarcinoma. Ultrasound-guided puncture of a distal branch of the right portal system is performed and the needle exchanged over a wire for a 5-Fr or 6-Fr vascular sheath. A flush catheter can then be advanced into the main portal vein and flush portography and pressure measurements performed. A 5-Fr reverse curve catheter such as an SOS-2 (Angiodynamics) or a Simmons 1 (Terumo) is subsequently inserted via the sheath and used to catheterize the right portal vein branches for embolization.
Embolization Extended to Include Segment 4
Before extended right hepatectomy, some authors have argued for extending right PVE to include segment 4 (RPVE + 4) as a means of improving hypertrophy of segments 2 and 3.77 The drawback is that catheter manipulation into branches feeding segment 4 is more technically demanding and inadvertent reflux of embolic material to the FLR has been reported.78,79 Capussotti et al.78 evaluated 26 patients who underwent RPVE (n = 13) or RPVE + 4 (n = 13) and found no difference in the volume increase (P = .20) or rate of increase (P = .40) of segments 2 and 3 in the two groups. However, recent studies comparing RPVE and RPVE + 4 have reported improved hypertrophy of segments 2 and 3 when segment 4 is also embolized, without increased incidence of complications.10,80,81 Kishi et al.80 compared patients who underwent RPVE (n = 15) versus those who underwent RPVE + 4 (n = 58). Compared to RPVE alone, the RPVE + 4 group demonstrated a greater absolute increase in segments 2 and 3 volume (median, 106 mL vs. 141 mL; P = .044) as well as a higher hypertrophy rate for segments 2 and 3 (median, 26% vs. 54%; P = .021). The complication rates were similar for RPVE and RPVE + 4 groups (7% vs. 10%; P > .99) and no PVE complication precluded resection.
Various materials and devices exist for embolization, and some of these have been adapted for the portal system. Commonly reported agents include polyvinyl alcohol, gelfoam, fibrin glue, N-butyl cyanoacrylate (NBCA), polidocanol foam, microspheres, Ethiodol, coils, and Amplatzer Vascular Plugs (St. Jude Medical, Inc., St. Paul Minnesota) among others.82,83 An ideal material will provide permanent portal venous embolization that is safe and well tolerated by the patient.74 The two agents most commonly discussed currently are NBCA and microspheres in combination with coils. To date, there has been no prospective randomized trial comparing the two.
Multiple studies have demonstrated the safety and effectiveness of small particle embolization of the liver with both PVA and microspheres.20,84 After catheterization of the portal system, embolization of distal small veins is performed with 100- to 300-µm particles. More proximal veins are embolized with larger particles with a goal of near stasis of flow or stasis. Coils are placed behind particles to prevent later particle dislodgement and recanalization.
NBCA has been shown to produce portal venous occlusion for more than 4 weeks85 and has been shown to induce a larger FLR when compared coils and gelatin sponge.73 NBCA induces an inflammatory reaction resulting in peribiliary fibrosis,73 and rates of liver regeneration are believed to be as good as or better than other embolic agents. However, preparation and administration require advanced knowledge and experience, and the inflammatory reaction sometimes renders surgical resection more difficult.73 Nontarget embolization has been reported and a technique has been developed to prevent backflow by placing a nitinol plug.86 NBCA is mixed with ethiodized oil and is delivered through an end-hole angiographic catheter from second- or third-order portal branch to prevent nontarget embolization. Straight catheters are preferred by some operators to prevent gluing of catheters into the liver, and great care must be taken to prevent embolization of NBCA to nontarget areas.
PORTAL VEIN EMBOLIZATION IN CONJUNCTION WITH TRANSARTERIAL THERAPY
Although PVE typically leads to reliable rates of hypertrophy, liver regeneration can be variable, especially when comorbidities such as underlying hepatic dysfunction or diabetes are present. When FLR hypertrophy is inadequate after PVE, adjunct therapies such as transarterial embolization (TAE) can be performed. The mechanism of TAE is complementary as a component of inflammation and necrosis is added to the apoptosis-mediated cell death induced by PVE to stimulate liver hypertrophy. In fact, arterial embolization alone has been shown to induce hypertrophy of the FLR, although to a lesser degree compared to PVE.87
Nagino et al.77 first described the use of TAE to improve FLR volume in two patients with cholangiocarcinoma who demonstrated inadequate hypertrophy following PVE. In both patients, PVE in the setting of underlying liver disease led to negligible hypertrophy of the FLR at 58 days (patient 1) and 14 days (patient 2). After TAE, the FLR volume increased from 470 to 685 mL (46%) 2 weeks after TAE (patient 1) and from 649 to 789 mL (22%) 3 weeks after TAE (patient 2) and both patients underwent successful curative resection. In this study, only half of the target segments were treated due to the potential risk of hepatic infarction given that both portal and arterial systems were disrupted. Similarly, Gruttadauria et al.88 reported inadequate hypertrophy after PVE in two patients with colorectal metastasis who demonstrated improved hypertrophy after TAE, allowing for subsequent successful hepatectomy.
TAE can also be performed as a staged procedure before PVE, with an interval of 2 to 3 weeks between the procedures to help prevent hepatic infarction.89,90 Aoki et al.89 reported the use of sequential transcatheter arterial chemoembolization (TACE) followed within 2 weeks by PVE in 17 patients with HCC. Sixteen of the 17 patients were able to undergo staged hepatectomy with no episodes of postoperative hepatic insufficiency. Analysis of the explanted livers demonstrated profound tumor necrosis without substantial injury to the noncancerous liver, and the authors therefore encourage the aggressive use of this strategy in patients with large HCC and chronically injured livers. In this patient population, the rationale for performing TACE before PVE includes prevention of tumor progression after PVE, reduction of arterioportal shunts that may limit the effectiveness of the subsequent PVE, and boosting the regenerative stimulus in chronically diseased livers. Ogata et al.90 performed sequential TACE and PVE versus PVE alone in a series of 36 patients with HCC and chronic liver disease before right hepatectomy. Patients in the combined chemoembolization (TACE) and PVE group (n = 18) demonstrated a higher mean increase in percentage of FLR volume (12% vs. 8%; P = .022) than those who underwent PVE alone (n = 18). The incidence of complete tumor necrosis (83% vs. 6%; P < .001) and 5-year disease-free survival rate (37% vs. 19%; P = .041) were also significantly higher in patients who underwent TACE and PVE.
In 2010, the Society of Interventional Radiology established quality improvement guidelines for transcatheter embolization, including a suggested threshold for PVE-related major complications of 6% and morbidity of 11%.91 Most published complication rates fall well below this range.92 A meta-analysis by Abulkhir et al.17 pooled data from 37 studies from 1990 to 2005 for a total of 1,088 subjects who underwent PVE and found the pooled procedure-related morbidity and mortality to be 2.2% and 0%, respectively. In this analysis, percutaneous PVE was performed in most cases (72%); the remainder was performed via the transileocolic technique. Complications of PVE are similar to other image-guided transhepatic procedures and include subscapular hematoma, hemoperitoneum, hemobilia, abscess formation, cholangitis and sepsis, arterioportal shunts, arterioportal fistula, and pneumothorax. In addition, PVE-specific complications include nontarget embolization, recanalization of embolized segments, and extension of portal vein thrombosis to involve the left or main branches. Kodama et al.76 compared complication rates between contralateral (n = 11) and ipsilateral approaches (n = 36) in a series of 47 patients who underwent PVE. Contralateral approach PVE was associated with an 18.1% complication rate as compared to 13.9% for ipsilateral PVE. Although the difference did not reach statistical significance, the authors recommended ipsilateral approach due to the potential for injury to the FLR during contralateral approach. Di Stefano et al.93 reported on 188 patients who underwent contralateral approach PVE and found a 12.8% adverse event rate and only one major complication (complete portal vein thrombosis) directly related to the contralateral approach that precluded surgery.93 Ribero et al.10reported on 112 patients who underwent ipsilateral approach PVE and found an 8.9% adverse event rate. Accounting for the fact that Di Stefano et al.93 included clinically occult CT findings in their complications, the rates are comparable between the two studies.
TIPS AND TRICKS
• Not all livers are created equal.
• There is significant variation in segmental and portal venous anatomy (see Fig. 31.7)
• Volumetry cutoffs need to be adjusted depending on the underlying baseline liver function: For normal livers, PVE should be considered for sFLR less than 20%; for cirrhotics, PVE should be considered for sFLR less than 40%.
• Chemotherapy affects baseline liver function, and PVE should be considered for sFLR less than 30%, especially if chemotherapy duration is more than 3 mo (see Fig. 31.6).
• PVE is an adjunctive technique to surgery.
• Contraindications to surgery serve as contraindications to PVE.
• Two-stage hepatectomy has increased the number of surgically resectable candidates, thus expanding the number of patients eligible for PVE.
• There are multiple ways to measure liver regeneration; choose one that is accurate and clinically relevant.
• Liver volumes must be normalized to a patient’s size.
• sFLR as calculated with CT volumetry has been clinically validated as an accurate and reproducible measure of postoperative hepatic insufficiency (see Fig. 31.2).
• Kinetic growth rate may serve as a more accurate predictor of postoperative hepatic insufficiency (see Fig. 31.5).
• Choose your percutaneous approach wisely (contralateral vs. ipsilateral).
• Ipsilateral approach avoids FLR injury and allows easy access to segment 4 (see Fig. 31.8).
• Contralateral approach allows direct access to right portal vein branches.
• Choose your embolic agent at your discretion.
• No clear evidence to suggest improved efficacy of a particular embolic agent.
• Choice should depend on operator experience/comfort level and anatomic considerations including variant anatomy and extent of embolization.
• Embolize the entire tumor-bearing liver.
• Right PVE in addition to segment 4 embolization (RPVE + 4) results in increased liver hypertrophy as compared to RPVE.
• When performing RPVE + 4, start with segment 4; if RPVE is performed first and there is thrombosis in the left portal vein, it is potentially catastrophic.
• There are no reports of increased complications with RPVE + 4 as compared to RPVE alone.
• PVE does not preclude TAE; in fact, they may be complementary.
• Transarterial embolotherapy can be done in a staged fashion before PVE to prevent tumor progression and boost the regenerative stimulus of chronically diseased livers.
• In select cases, transarterial embolotherapy can be performed after PVE to further promote liver hypertrophy.
PVE is well established worldwide as an adjunctive procedure before hepatectomy to induce FLR hypertrophy. PVE has been shown to reduce perioperative morbidity and allows for safe, potentially curative hepatectomy in patients previously considered ineligible for resection based on anticipated small remnant livers. PVE continues to demonstrate an essential adjunctive role to major hepatectomy, even as advances in hepatobiliary surgical techniques evolve and indications for curative hepatectomy expand, given its high safety profile and proven efficacy at promoting liver remnant hypertrophy.
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