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Portal Vein Embolization (PVE): Methods, History, Indications, and Related Concepts

Introduction

The most important innovation in preoperative management of patients undergoing liver resection includes biliary drainage, which has shifted from percutaneous transhepatic to endoscopic nasobiliary methods, and the use of portal vein embolization (PVE) for volume modulation.

Historical Perspective

Contributions of Masatoshi Makuuchi

Masatoshi Makuuchi (1946) is considered one of the most innovative surgeons at the end of the 20th century—a true Leonardo Da Vinci of liver surgery.

  • Makuuchi's Innovations:
    • Established safety limits for the extent of liver resection in injured livers using the indocyanine green (ICG) tolerance test, included in the "Makuuchi criteria" for hepatic resection.
    • Described the extrahepatic division of the right hepatic vein in hepatectomy.
    • Introduced intraoperative ultrasound (IOUS) for the safety and quality of liver resections.
    • Conceived preoperative PVE, which increases the volume of the future remnant liver (FLR) and enhances tolerance of liver resection.
    • First in the world to perform surgery with an adult living donor, further developing criteria for venous reconstruction.
    • Advocated hemihepatic vascular occlusion during liver resection to avoid splanchnic congestion and preserve vascularization of the remnant liver.

Impact of Postoperative Morbidity on Survival

The impact of postoperative morbidity on survival after resection of malignant tumors emphasizes the importance of measures such as:

  • Preservation of venous drainage of the liver remnant.
  • Use of PVE to increase safety and efficacy of liver resections.

Adoption and Evolution of PVE

  • In the 1990s, PVE before major liver resection was widely adopted due to its:
    • Technical simplicity.
    • Tolerance by patients.
    • Efficiency in inducing hypertrophy of the FLR.

Expansion of Preoperative Modulation Techniques

  • Use of arterial embolization or hepatic vein occlusion in combination with PVE.
  • Introduction of the Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy (ALPPS) procedure:
    • Proposed by Santibañez (Buenos Aires, Argentina) and Clavien (Zurich, Switzerland).
    • High-risk, dual complex surgical procedure.
    • Does not consider the natural oncologic history.
    • Imposes a long hospital stay, conflicting with Enhanced Recovery After Surgery (ERAS) principles.
    • Remains localized to certain centers due to its risks.

Parenchymal-Sparing Hepatectomy

  • Developed by Guido Torzilli in 2005.
  • A conservative approach to multiple liver resections.
  • Offers advantages over major hepatectomy in terms of tolerance without impairing survival.

Clinical Relevance of Liver Regeneration

Hepatobiliary surgery relies on the liver's ability to regain functional mass rapidly.

  • Factors limiting curative tumor resection include insufficient volume of the liver remnant.
  • Techniques to increase liver remnant volume:
    • Portal Vein Embolization (PVE)
    • Portal Vein Ligation (PVL)
    • Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy (ALPPS)

Significance in Transplantation

  • Success in living donor liver transplantation (LDLT) relies on hepatic regeneration in both donor and recipient.
  • Minimal functional liver necessary for transplantation is a major concern.
  • Donor graft size, recipient weight, and portal hypertension influence regeneration needs.

Liver Atrophy

  • Atrophy is triggered by obstruction of portal venous blood flow and/or chronic bile duct obstruction.
  • When atrophy occurs unilaterally:
    • The opposite lobe responds with hypertrophy.
    • Utilized in surgical techniques like PVE and ALPPS.
  • In slow-onset atrophy:
    • Significant distortion of the liver occurs.
    • Anatomic landmarks can change markedly, often accompanied by rotation of the liver and portal triad structures.

Indications for Portal Vein Embolization (PVE)

General Indications

  • Future Liver Remnant (FLR) less than 25% in normal healthy liver.
  • FLR less than 30% in chemotherapy-induced liver toxicity.
  • FLR less than 40% in patients with cirrhosis and underlying liver dysfunction.

Specific Patient Populations

  • Cholangitic patients, jaundiced patients requiring systemic chemotherapy.
  • Patients with hyperbilirubinemia-induced malnutrition.
  • Those with hepatic insufficiency.
  • Jaundiced patients undergoing PVE require immediate biliary decompression.

Portal Vein Embolization (PVE): Methods and Outcomes

Procedural Evolution

  • First described by Makuuchi et al. in cases predicting an inadequate FLR.
  • Originally required a transileocolic approach.
  • Now commonly performed via percutaneous transhepatic approach:
    • Obviates the need for general anesthesia and laparotomy.

Assessment of Liver Hypertrophy

  • Kinetic Growth Rate (KGR):
    • Calculated by the degree of hypertrophy over the number of weeks since PVE.
    • Highly predictive of postoperative liver failure.
    • No patients with a KGR greater than 2.66% per week experienced postoperative liver insufficiency.

Safety and Efficacy

  • Safe procedure with low morbidity (2%–2.5%) and mortality (0.1%) rates.
  • Increases FLR by an absolute value of 8% to 37.9%.
  • Preferred in cases where FLR is expected to be less than 40%.

PVE in Perihilar Cholangiocarcinoma (pCCA)

  • FLR volume below 40% to 50% is the most important modifiable risk factor for postoperative mortality.
  • PVE demonstrated to induce an increase in FLR volume in both healthy and compromised liver parenchyma.
  • Makuuchi presented initial results of PVE in 1990 in 14 pCCA patients without major side effects.
  • Meta-analysis by Jiao and colleagues:
    • PVE is safe and effective with a morbidity rate of 2.2% and no mortality.
    • Increase in remnant liver volume slightly larger after percutaneous transhepatic portal embolization compared to transileocolic portal embolization (11.9% vs. 9.7%).
  • Use of PVE associated with:
    • 4.4-fold reduction in liver failure.
    • Reduction in postoperative bile leakage by 3.5-fold.
    • Decrease in 90-day postoperative mortality from 18% to 7%.

Additional Techniques

  • Ipsilateral hepatic vein embolization may be performed if desired gain of volume by PVE is not accomplished.
  • Liver venous deprivation (combined hepatic vein embolization and PVE) has been reported as a safe approach leading to a superior degree of hypertrophy and KGR compared with PVE alone.

Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy (ALPPS)

Procedure Overview

  • ALPPS is a two-stage hepatectomy combined with in situ splitting of the liver and concomitant portal ligation during the first stage.
  • Leads to rapid hypertrophy of the FLR.
  • Associated with high perioperative morbidity (80%) and mortality rates (12%).

Use in Perihilar Cholangiocarcinoma (pCCA)

  • Initially performed for HC (hilar cholangiocarcinoma), now rare due to high complication rates.
  • International ALPPS registry reported a 90-day mortality rate of 27% in patients with HC.
  • ALPPS Italian registry group reported a 40% 90-day mortality rate for ALPPS performed for biliary tumors.
  • Matched case–control studies showed:
    • Mortality rate in the ALPPS group was twice as high.
    • Median survival was 6 months in the ALPPS group versus 29 months in the matched control group.
  • Modified ALPPS approaches have been suggested but not convincingly demonstrated to decrease morbidity in HC.
  • ALPPS is not recommended for pCCA due to high mortality and morbidity.

Use in Colorectal Liver Metastases (CLM)

  • ALPPS proposed as an alternative to conventional Two-Stage Hepatectomy (TSH) for CLM.
  • Concerns with TSH include drop-out due to disease progression.
  • ALPPS triggers accelerated FLR hypertrophy, enabling two-stage completion within 1 to 2 weeks.
  • Initial studies reported:
    • High morbidity and mortality rates.
    • High intrahepatic recurrence rates of up to 60%.
  • LIGRO trial:
    • Compared ALPPS with hepatectomy after portal vein occlusion.
    • No significant difference in major morbidity, 90-day mortality, and R0 resection between arms.
    • ALPPS enabled resection in 92% of patients versus 57% in the portal vein occlusion arm.

Strategies to Increase Resectability

Two-Stage Hepatectomy (TSH)

  • Sequential strategy for bilateral CLM not resectable in a single procedure.
  • First stage: Metastases in the FLR are resected.
  • Between stages: PVE performed if indicated to ensure adequate FLR volume.
  • Carries a risk of dropout between stages due to disease progression (11% of patients).
  • Completion rates improved with liver venous deprivation techniques.

Completion Ablation

  • Strategy to resect all but one to two small metastases and preserve liver parenchyma.
  • Remaining metastases treated with percutaneous ablation under CT guidance.
  • Associated with lower rates of postoperative complications and local tumor progression compared to intraoperative ablation.

Biliary Drainage

Purpose

  • Aims to restore the regenerative capacity of the FLR.

Indications for Preoperative Biliary Drainage

  • Cholangitis.
  • Jaundice and the need to undergo neoadjuvant therapy.
  • Liver or renal insufficiency possibly related to hyperbilirubinemia.
  • Small FLR volume (<50%), especially before PVE.

Patient Populations Requiring Immediate Biliary Decompression

  • Cholangitic patients.
  • Jaundiced patients requiring systemic chemotherapy.
  • Patients with hyperbilirubinemia-induced malnutrition.
  • Those with hepatic insufficiency.
  • Jaundiced patients undergoing PVE.

Impact of Diabetes Mellitus on Liver Regeneration

  • Insulin is a crucial hepatotrophic factor in portal venous blood.
  • Impaired insulin secretion in diabetic patients prevents liver regeneration after partial hepatectomy (PHx).
  • Findings:
    • Decreased RNA, DNA, and protein synthesis on the first postoperative day.
    • Enhancement of mitochondrial phosphorylate activity is inhibited proportionally to the severity of insulin impairment.
  • Diabetes mellitus is a risk factor for reduced hypertrophy after PVE.
  • Recommendations:
    • Strict glucose control is essential in liver surgery and PVE.

Volumetric Thresholds for Safe Hepatectomy

Thresholds in Patients with Normal Liver

  • Optimal cutoff for FLR is between 20% and 30%.
  • A 2006 expert consensus recommended a minimum of 20% FLR for major hepatic resection in patients with a healthy liver.
  • PVE should be considered for any FLR less than this threshold.

Thresholds in Patients After Chemotherapy

  • Patients who have received preoperative chemotherapy are at risk for background liver injury that impairs regeneration.
  • Optimal FLR thresholds reported:
    • 31% (Shoup et al.).
    • 48.5% (Kishi et al.).
  • Recommendations:
    • Patients with extensive chemotherapy or liver injury require a larger FLR.
    • Consider PVE when standardized FLR (sFLR) is less than 30%.
    • Patients with sFLR between 30% and 40% should be closely evaluated for liver dysfunction.

Thresholds in Patients with Underlying Liver Disease

  • Optimal FLR threshold is less certain.
  • Some authors advocate for PVE in all patients with chronic liver disease before right-side hepatectomy.
  • Others apply a conservative threshold as high as 40%.
  • Additional functional tests should be considered before major hepatectomy in the setting of significant liver disease.

Volumetry After Hypertrophy (Post-PVE)

Degree of Hypertrophy (DH)

  • Defined as the absolute difference between FLR before and after PVE.
  • DH appears to be more informative than post-PVE FLR alone.
  • Recommendations:
    • Patients without cirrhosis should have:
      • An sFLR of at least 20%.
      • A DH of at least 5% for safe hepatectomy.
  • PVE functions as a diagnostic test; lack of substantial FLR growth after PVE suggests potential background liver disease.

Kinetic Growth Rate (KGR)

  • KGR is calculated by dividing DH by the number of weeks since PVE.
  • Studies indicate:
    • KGR is a better predictor of postoperative hepatic insufficiency than absolute sFLR or DH.
    • A KGR less than 2% per week is associated with higher hepatic insufficiency and mortality.
    • No liver failure occurred in patients with a KGR greater than 2.66% per week.

MRI in Predicting Post-Hepatectomy Liver Failure (PHLF)

  • MRI has been shown to be superior to sFLR volume and ICG-R15 in predicting PHLF.
  • Key MRI parameters:
    • Relative Liver Enhancement (RLE): Difference in signal intensity between unenhanced and hepatobiliary phases.
    • Hepatocellular Uptake Index (HUI): Difference in signal intensity between liver parenchyma and spleen.
  • Studies suggest:
    • Functional FLR calculated using RLE correlates well with PHLF risk.
    • Increase in RLE from baseline to 14 days post-PVE is an excellent predictor of PHLF.
    • Beyond 14 days post-PVE, minimal improvements are seen in FLR, KGR, and RLE.

Regenerative Potential of the Liver After Chemotherapy

  • Increased complication rate and mortality after major liver resection in patients undergoing extensive chemotherapy.
  • Deleterious effects of chemotherapy on regeneration increase with the total number of cycles.
  • Recommendations:
    • Limit to no more than six cycles of FOLFOX/FOLFIRI chemotherapy before liver resection.
    • Allow a three-week interval between chemotherapy and surgery.
  • Bevacizumab considerations:
    • Long half-life; theoretically should be stopped 6–8 weeks before surgery.
    • Results from PVE under continuous bevacizumab showed no deterioration in FLR increase after four weeks.
    • Some studies report significantly impaired hypertrophy, potentially due to extensive chemotherapy.
    • Optimal window between completion of bevacizumab and surgery remains uncertain.

Radiologic Hepatobiliary Interventions

Vascular Procedures

Portal Vein Interventions

  • Portal Vein Embolization (PVE) is used to improve the safety of hepatic resection.
  • History of PVE:
    • First proposed by Makuuchi and colleagues in 1990.
    • Initially performed via a transileocolic approach requiring laparotomy.
    • Now commonly performed percutaneously, typically as an outpatient procedure.
  • Agents Used in PVE:
    • Ethanol, Gelfoam, thrombin, polyvinyl alcohol, glue, spherical embolic agents, coils, sclerosing agents.
    • No agent has proven superior; each increases FLR/TLV by approximately 8%–10%.
  • Complications:
    • Uncommon but may include nontarget embolization to the main portal vein or the portal vein supplying the FLR.
    • Such complications could preclude operation and occur in less than 1% of patients.

Key Terms:

  • Portal Vein Embolization (PVE)
  • Future Liver Remnant (FLR)
  • Indocyanine Green (ICG) Tolerance Test
  • Intraoperative Ultrasound (IOUS)
  • Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy (ALPPS)
  • Degree of Hypertrophy (DH)
  • Kinetic Growth Rate (KGR)
  • Post-Hepatectomy Liver Failure (PHLF)
  • Relative Liver Enhancement (RLE)
  • Hepatocellular Uptake Index (HUI)
  • Enhanced Recovery After Surgery (ERAS)
  • Standardized Future Liver Remnant (sFLR)
  • Partial Hepatectomy (PHx)
  • Living Donor Liver Transplantation (LDLT)
  • Cholangiocarcinoma (pCCA)
  • Two-Stage Hepatectomy (TSH)
  • Colorectal Liver Metastases (CLM)

This comprehensive guide consolidates all the provided information on Portal Vein Embolization (PVE) and Biliary Drainage, including methods, history, indications, and related concepts. It ensures that every sentence from the provided context is included, reorganized into a structured format with headings, subheadings, bullet points, and highlighted key terms for clarity and ease of study.

Portal Vein Embolization (PVE) [102C BLG]

Introduction

  • Portal Vein Embolization (PVE) is the most common portal flow modulation procedure performed preoperatively to reduce the risk of extensive liver resection in patients with a small anticipated Future Liver Remnant (FLR) volume.
  • PVE redirects portal blood flow to the intended FLR, causing atrophy of the embolized liver and compensatory hypertrophy of the FLR.
  • This procedure can reduce perioperative morbidity and allow for safe, potentially curative hepatectomy in patients previously considered ineligible due to a small FLR.
  • PVE is widely performed at hepatobiliary centers worldwide before major hepatectomy.

Evaluation of Future Liver Remnant Volume to Predict the Safety of Major Hepatectomy

Systematic Volumetry

  • The safety of extensive liver resection depends on the functional reserve of the FLR.
  • FLR volume and the liver's regenerative capacity are critical predictors of postoperative morbidity and mortality.
  • Routine volumetry using validated methods is recommended, especially for patients undergoing extended right hepatectomy.
    • Only 25% of patients have sufficient FLR volume (!20% of estimated standard liver volume) for safe extended right hepatectomy.
    • 90% of patients have sufficient FLR volume for right hemihepatectomy.
  • FLR Volume Calculation:
    • Calculated as the absolute volume of the functioning liver after resection.
    • Excludes parts that will be congested due to loss of normal inflow and outflow (e.g., after removal of a hepatic vein).
    • For extended right hepatectomy with removal of the middle hepatic vein, segment IV volume is not included in FLR volume.

Minimal Future Liver Remnant Volume Required for Safe Liver Resection

  • Various methods evaluate the risk of major hepatectomy based on FLR volume.
  • Japanese Centers:
    • Use three-dimensional (3D) image reconstruction systems for volumetry.
    • Indocyanine Green (ICG) Clearance Test is used to determine functional reserve.
    • An ICG-Krem (estimated ICG clearance rate of FLR) of ≥0.05 is predictive of the maximum limit of liver resection.
  • Limitations:
    • Requires high-quality thin-slice CT images.
    • ICG clearance test may not be available in all countries.
  • MD Anderson Cancer Center Approach:
    • Use Standardized FLR (sFLR) Volume:sFLR = Measured FLR Volume / Estimated Total Liver Volume (TEL)
    • TEL is estimated using the patient's Body Surface Area (BSA):TEL (cm³) = -794.41 + 1267.28 × BSA (m²)
    • Advantages:
      • Avoids direct measurement errors.
      • Reflects hepatic physiological needs based on patient size.
  • sFLR Cutoff Values for Safe Resection:
    • Normal Liver: sFLR ≥20%
    • Chemotherapy-Induced Liver Injury: sFLR ~30%
    • Cirrhosis: sFLR ≥40%

Indications and Contraindications for PVE

  • Indications:
    • When the FLR or sFLR is insufficient for safe hepatectomy considering liver quality and surgery extent.
  • Absolute Contraindications:
    • Established portal hypertension
    • Extensive tumor thrombus in the ipsilateral portal vein
  • Considerations:
    • Mild subclinical portal hypertension is not an absolute contraindication.
    • PVE may worsen symptoms of portal hypertension due to increased portal vein pressure.

Technical Aspects of Portal Vein Embolization

Access Routes to the Portal Venous System

  1. Transileocolic Venous Approach
    • First approach described for PVE.
    • Performed via laparotomy by cannulating the ileocolic vein.
    • Use Cases:
      • Additional intraoperative treatments.
      • Percutaneous approach not feasible.
      • Lack of interventional radiology suite.
    • Disadvantages:
      • Requires general anesthesia and laparotomy.
      • Higher risks and inferior imaging compared to modern interventional radiology.
  2. Percutaneous Transhepatic Contralateral Approach
    • Ultrasound-guided percutaneous puncture of a portal branch in the FLR (preferably segment III).
    • Advantages:
      • Easier catheterization of right portal branches.
      • Embolization in the direction of portal blood flow.
    • Drawbacks:
      • Instruments pass through the FLR, risking injury.
      • Complications may involve the FLR, affecting planned surgery.
  3. Percutaneous Transhepatic Ipsilateral Approach
    • Access through portal branches in the tumor-bearing liver.
    • Advantages:
      • No instruments in the FLR.
      • Straightforward catheterization of segment IV if needed.
    • Challenges:
      • Difficult catheterization of right portal branches due to sharp angles.
      • May require specialized catheters (reverse-curve or balloon occlusion catheters).

Optimal Extent of Embolization

  • Debate on Extent:
    • Right PVE alone vs. Right PVE extended to Segment IV.
  • Benefits of Extending to Segment IV:
    • Greater FLR Hypertrophy:
      • Nagino et al.: 50% increase with segment IV embolization vs. 31% with right PVE alone.
    • No Increase in Complications.
    • Reduced Tumor Growth Risk:
      • Embolizing entire tumor-bearing liver decreases portal flow to tumors.

Sequential Arterial Embolization and PVE

  • Used in HCC with Chronic Liver Disease.
  • Justifications:
    • Compromised regenerative capacity in cirrhotic livers.
    • Arterioportal shunts may limit PVE effectiveness.
    • Prevents tumor progression due to increased arterial flow post-PVE.
  • Method:
    • Transcatheter Arterial Chemoembolization (TACE) followed by PVE within 2–4 weeks.
  • Benefits:
    • Enhances FLR hypertrophy.
    • Increases tumor necrosis.
    • Does not significantly injure noncancerous liver tissue.

Liver Venous Deprivation (LVD)

  • Simultaneous Hepatic Vein Embolization (HVE) with PVE.
  • Benefits:
    • Enhances hypertrophy of FLR.
    • Kobayashi et al. reported superior hypertrophy and kinetic growth rates compared to PVE alone.
  • Considerations:
    • Optimal use (routine vs. selective) is under investigation.
    • Potentially beneficial for patients with very small FLR.

Degree and Speed of Hypertrophy and Risk of Postoperative Hepatic Insufficiency

  • FLR Regeneration Rate is crucial.
  • Key Predictors:
    • Dynamic Hypertrophy (DH): Change in sFLR volume divided by pre-PVE sFLR volume.
    • Kinetic Growth Rate (KGR): DH divided by weeks elapsed post-PVE.
  • Optimal Values:
    • DH >5%
    • KGR ≥2.0% per week associated with low risk of hepatic insufficiency.
  • Implications:
    • High DH and KGR predict better surgical outcomes.
    • Important even for patients with small initial sFLR or extensive chemotherapy-induced liver injury.

Complications of Percutaneous Portal Vein Embolization

  • Potential Complications:
    • Subcapsular Hematoma
    • Hemoperitoneum
    • Hemobilia
    • Arterioportal Shunts
    • Arteriovenous Fistula
    • Pseudoaneurysm
    • Portal Vein Thrombosis
    • Transient Liver Failure
    • Pneumothorax
    • Sepsis
  • Incidence:
    • Generally low, with minimal differences between approaches.
    • MD Anderson reported complications in 3.9% of patients.

Clinical Outcomes

Short-Term Surgical Outcomes

  • Major Complication Rate after PVE and major hepatectomy: ~25.8%.
  • 90-Day Liver-Related Mortality: ~3.8%.
  • Risk Factors for Mortality:
    • Older age
    • Male gender
    • Preoperative chemotherapy
    • Smaller sFLR
    • Lower DH and KGR post-PVE
  • Trend: Decreased complication rates over time despite higher-risk patients.

Long-Term Surgical Outcomes

Hepatocellular Carcinoma (HCC)

  • No significant difference in survival rates between patients requiring PVE and those who did not.
  • Postoperative Mortality: 0% in patients who had PVE before resection vs. 18% in those operated upfront.
  • 5-Year Survival Rates: 72% in PVE group vs. 54% in non-PVE group.

Biliary Tract Cancer

  • PVE allows safe extended hepatectomy.
  • Ebata et al. reported:
    • 372 out of 494 patients (75.3%) underwent successful resection post-PVE.
    • 5-Year Survival Rates: 39% for cholangiocarcinoma, 23% for gallbladder cancer.

Colorectal Liver Metastases (CRCLMs)

  • PVE increases resectability and improves survival.
  • Wicherts et al.:
    • Patients resected after PVE had better 3- and 5-year survival than those unresectable.
  • MD Anderson Findings:
    • Similar long-term outcomes for patients requiring PVE and those who did not.

Outcomes in Patients with Very Small Future Liver Remnant

  • PVE enables patients with sFLR ≤20% to have postoperative outcomes similar to those with larger sFLR.
  • Rivers et al.:
    • 144 patients with very small FLR underwent PVE extended to segment IV.
    • 104 patients (72.2%) proceeded to curative resection.
    • Morbidity: 33.0%
    • Hepatic Insufficiency: 12.5%
    • 90-Day Liver-Related Mortality: 5.8%
  • Conclusion:
    • Right PVE plus Segment IV Embolization should remain standard care for patients with very small FLR.

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