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

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Introduction

• ALPPS is a modification of the two-staged liver resection combining two established surgical techniques: right portal vein ligation (PVL) and in situ splitting of the liver (ISS).
• The first large series introducing this novel technique was published as a multicenter experience of German surgeons.
• Dr. Hans Schlitt initiated the concept of ALPPS in 2007 during exploration of a patient with hilar cholangiocarcinoma resectable by right trisectionectomy.
  • Due to the patient's long-standing cholestatic condition and small size of the future liver remnant (FLR), Schlitt abandoned the resection.
  • Instead, he performed a hepaticojejunostomy for drainage of the FLR after dividing the liver and ligating the right portal vein.
  • A CT scan on postoperative day 9 revealed a dramatic hypertrophy of the FLR of about 90%.
  • Schlitt and his group called this procedure "right portal vein ligation with in situ splitting."
• Later, the acronym ALPPS was introduced and is now accepted worldwide.

Indications

• Main Indication:
  • Bilateral colorectal cancer liver metastases (CRCLM)
    • Most cases of ALPPS have been performed for this indication.
    • CRCLM is the most promising indication, especially for bilobar metastases.
• Other Indications:
  • Hepatocellular carcinoma (HCC)
    • Typically arises in the cirrhotic liver.
    • Has been resected by ALPPS.
    • Data from Asia are convincing but probably not reproducible elsewhere; thus, these data must be interpreted with caution.
  • Perihilar (PHC) and Intrahepatic (IHC) Cholangiocarcinoma
    • Vigorously discussed in the surgical community, with no final agreement.
    • Tendency to be very cautious due to reported high mortality.
    • In some selected cases, ALPPS may be the only operative option.
    • It is important to remember that the first successful case was performed in a patient with PHC.
    • If ALPPS is used in PHC, preoperative biliary drainage is advised.
• Consider ALPPS When:
  • A major liver resection is needed and the FLR is insufficient during preoperative workup.
  • An extreme volume gain is required; ALPPS could have an advantage over other methods.
  • Tumor load in the FLR; ALPPS or classic two-stage hepatectomy is more appropriate than PVE because the FLR can be cleared of tumor during the first stage.
  • PVE or classic two-stage approach is not feasible or has failed ("rescue ALPPS").
  • Some authors advise attempting PVE first, then proceed with ALPPS if hypertrophy response is insufficient.
• Potential Additional Procedures:
  • Combination with resection of the colorectal primary tumor has been performed.
  • Represents a potential indication, but caution is advised due to increased surgical risk.
• Contraindications:
  • Extrahepatic metastases
  • Severe portal hypertension
  • High anesthesiologic risk
  • Medical contraindications to major hepatectomy
  • These constitute clear contraindications to performing this procedure.

Assessment of Future Liver Remnant (FLR)

• Importance of FLR Assessment:
  • Key determinant in planning for ALPPS.
  • Must be performed before surgery and reevaluated before the second stage.
• Methods of Assessment:
  • CT Volumetry:
    • Using thin sections (1–2 mm).
    • Preferably carried out by a radiologist and a liver surgeon.
    • 3D reconstructions calculate nontumorous liver volume, tumor volume, and FLR volume.
  • Cutoff Values for Safe Resection:
    • 20% in patients with a normal liver.
    • 30–35% in patients with chemotherapy-related liver injury.
    • 40% in patients with chronic liver disease.
  • Standardized FLR (sFLR) Volume or Body Weight Ratio (BWR):
    • Alternative personalized methods.
    • Cutoff values for proceeding to stage 2:
      • sFLR >30% (BWR ≥0.5%)
      • sFLR >40% (BWR ≥0.8%), depending on parenchymal quality.
• Degree of Hypertrophy:
  • Various degrees reported after stage 1.
  • CT volumetry may be unreliable in patients with hepatic comorbidities.
  • Hepatobiliary Scintigraphy (Technetium-99m Mebrofenin):
    • Quantitative liver function test.
    • Used as a predictor of insufficient functional hypertrophy after PVE.

Surgical Technique

Anatomic Aspects

• Portal Vein (PV) Variations:
  • PV trifurcation with separate entries of right anterior and posterior sectional branches in 15–26% of populations.
  • Missing an anterior sectional PV originating from the left PV can lead to incomplete deportalization.
  • Intraoperative ultrasound helps avoid technical failures.
  • An undivided PV at the hilum is rare but is an absolute contraindication to ALPPS.
• Biliary Anatomy Variations:
  • Bile leakage is a major morbidity factor.
  • Leaks often originate from segment IV bile ducts.
  • According to Smadja and Blumgart classification:
    • Type A (normal anatomy) and Type B (trifurcation): No increased risk.
    • Type C and D variations: Higher risk of biliary complications.
      • Type C: Aberrant drainage into the common hepatic duct.
      • Type D: Aberrant drainage into the left hepatic duct.
    • Type E (absence of hepatic duct confluence): Greater risk during stage 2.
  • Minimize dissection at the hilum to preserve arterial plexus.
  • Intraoperative cholangiography helps identify anomalies.
• Arterial Variations:
  • Common and influential, especially in segment IV supply.
  • Risk of dividing the segment IV artery during partition.
  • Loss of segment IV artery increases necrosis risk.
  • Preservation is crucial if segment IV is retained.
• Hepatic Venous Drainage:
  • Multiple patterns exist.
  • Middle hepatic vein (MHV) is crucial.
    • Receives tributaries from segment IV (left) and segments V and VIII (right).
  • MHV should not be transected during stage 1 unless infiltrated by tumor.

Surgical Procedure

• Types of ALPPS:
  • Various modifications, including partial ALPPS.
    • Transection of only 50% of liver parenchyma.
    • Similar hypertrophy with reduced morbidity.
  • Complete transection needed only if risk of tumor progression into FLR exists.
• Surgical Approach:
  • Open surgical technique is most common.
  • Laparoscopic variants have been reported.
    • Similar completion rates and shorter hospital stays.
  • Complete robotic ALPPS has also been performed.

Stage 1

• Assessment and Mobilization:
  • Assess parenchyma macroscopically; biopsy if necessary.
  • Mobilize right liver by dissecting all ligaments.
  • Dissect retroperitoneal adhesions; expose vena cava.
  • Confirm resectability with intraoperative ultrasound.
• Lymphadenectomy:
  • Advised for oncologic reasons and hilar structure identification.
• Portal Vein Division:
  • Divide the right PV branch; sew over or use a vascular stapler.
• Parenchymal Dissection:
  • Divide and close all portal and biliary segment IV branches.
  • Total or partial parenchymal dissection using anterior approach.
  • Use ultrasound dissector or LigaSure with bipolar coagulation.
• Preservation:
  • Leave arterial structures and venous drainage of right liver intact.
  • Tag right hepatic artery and bile ducts with vessel loops for stage 2.
• Detecting Biliary Leaks:
  • Perform a "white test" with a T-tube or cystic duct catheter.
• Covering Resection Plane:
  • Use a plastic bag or hemostatic patch to prevent adhesions.
  • Note: If stage 2 isn't performed, the foreign body must be removed.
• Middle Hepatic Vein (MHV):
  • Debate on dividing MHV during stage 1.
  • Preserving MHV avoids venous drainage issues.
• Tumor Excisions in FLR:
  • May be necessary to render FLR tumor-free.
• Drain Placement:
  • Place at least one drain near the resection surface.

Interval Phase

• Monitoring Hypertrophy:
  • Perform abdominal CT scan one week post-operation.
  • Calculate FLR volume, total liver volume (TLV), and volume gain.
• Criteria for Stage 2:
  • sFLR >30% (BWR ≥0.5%)
  • sFLR >40% (BWR ≥0.8%), depending on parenchymal quality.
• Timing:
  • Usual interval is 7–14 days between stages.

Stage 2

• Completion of Hepatectomy:
  • Remove deportalized lobe, completing extended hemihepatectomy.
• Anatomical Considerations:
  • FLR hypertrophy may displace hepatic pedicle; proceed with caution.
• Ligating Structures:
  • Ligate and cut right hepatic artery and bile ducts.
  • Divide right (and possibly middle) hepatic vein near vena cava.
• Final Steps:
  • Divide any remaining parenchymal bridges.
  • Intraoperative cholangiography may be performed to ensure biliary continuity.
• Variations:
  • Applicable for extended right hemihepatectomy, left hemihepatectomy, or central ALPPS.

Pathophysiologic Aspects

• Mechanisms of Hypertrophy:
  • In situ split cuts off portal collateral communications, enhancing hypertrophy.
  • Surgical trauma releases cytokines that promote liver regeneration.
• Arterial Hyperperfusion:
  • Deportalized lobe compensates with increased arterial blood flow.
  • Maintains oxygen supply and function until FLR gains sufficient volume.
• Effect of Chemotherapy:
  • Neoadjuvant chemotherapy does not negatively affect FLR growth.
• Research Models:
  • Animal models developed to study ALPPS mechanisms.

Results

• Morbidity and Mortality:
  • Initial reports showed high rates, sparking debate over safety.
  • Common complications:
    • Posthepatectomy liver failure
    • Biliary fistulae
    • Infected collections
    • Sepsis
• Improved Outcomes:
  • Better results with increased experience and technical refinements.
  • Contributing factors:
    • Accurate 3D volumetric calculation
    • Use of partial ALPPS
    • Colored plastic loops during stage 1
    • Intraoperative cholangiography
    • White test for biliary leaks
    • Preserving the MHV
• International ALPPS Registry Findings:
  • 9% perioperative 90-day mortality in 202 patients.
  • 28% severe complications (Clavien-Dindo grade ≥IIIa).
  • Risk factors: red blood cell transfusion, surgery duration >300 minutes, age >60 years.
• Reducing Morbidity and Mortality:
  • Recommendations based on complications data.
  • Centers performing >10 ALPPS procedures in 3 years saw mortality drop from 9% to 4%.
  • Indication for ALPPS is crucial; primary liver cancer patients have more severe complications.
• Posthepatectomy Liver Failure:
  • Leading cause of death and severe complications.
  • Occurs even when FLR volume seems sufficient.
  • Functional tests needed, as volume gain may not equal functional increase.
• Timing of Stage 2:
  • Majority of lethal outcomes occur after stage 2.
  • Patients should be in good clinical condition with near-normal liver function tests.
  • Stage 2 timing should be flexible; not always within first 2 weeks.
• Long-Term Outcomes:
  • CRCLM is the main current indication.
  • 1-year survival ranges from 76–93% in series with >10 patients.
  • 2-year survival reported at 62% in some studies.
  • 3-year overall survival around 56%.
  • Early recurrence common, with a mean recurrence time of 9 months.
  • Disease-free survival ranges from 50–67% after 1 year.
  • ALPPS may enhance tumor proliferation, similar to PVE or classic two-stage hepatectomy.
• Comparative Studies:
  • Ligro-Trial: No difference in perioperative complications between ALPPS and two-stage hepatectomy.
  • ALPPS had a better resection rate.
  • Recent meta-analysis shows higher mortality and morbidity in ALPPS but similar liver-related mortality.

Conclusion

• ALPPS is a two-stage liver resection technique allowing resection in patients with insufficient FLR volume.
• Rapid hypertrophy allows stage 2 to be performed in 7–14 days.
• Morbidity and mortality rates have decreased with experience and partial ALPPS application.
• ALPPS complements rather than replaces traditional methods like PVE or two-stage resection.
• "Rescue ALPPS" can be performed if hypertrophy after PVE or PVL is insufficient.
• Future challenges include confirming that ALPPS does not increase cancer progression.
• ALPPS is now an established technique, though optimal methods and patient selection continue to be studied.

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