ALPPS: Safety, Feasibility and Efficacy at a Single Center

Study Overview
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Brief Summary
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The possibility to achieve a curative resection in patients with liver malignancies is limited by the future liver remnant (FLR). The Associating Liver Partition and Portal vein ligation for Staged hepatectomy (ALPPS) approach has recently been introduced as a revolutionary strategy to achieve resectability by inducing a rapid and large FLR hypertrophy. However, the possibility of achieving a short-term hypertrophy and high resectability rates has been counteracted in most published series by an increased risk of morbidity and mortality.The aim of this study was to evaluate the results with the ALPPS procedure in a single high-volume HPB center, with special emphasis in the safety and feasibility of this new 2-stage strategy. The aim of the present study was to assess the safety, feasibility and efficacy of ALPPS in a single high-volume hepatobiliary center.

Detailed Description
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Complete resection of liver malignancies remains as the best treatment to offer the possibility of long-term survival or cure. At diagnosis, many patients have locally advanced disease that often precludes a curative resection. During the past two decades, a better assessment of resectability through modern imaging techniques along with new multimodal therapies and the introduction of modern chemotherapy regimens have allowed to increase the pool of candidates for surgical treatment in patients with locally advanced disease. The current principles for safe liver resections focus mainly on the liver parenchyma that remains after resection rather than the liver resected. In fact, one of the main conditioning factors of posthepatectomy liver failure (PHLF) is the amount and quality of future liver remnant (FLR). The induction of hypertrophy of healthy parenchyma using either portal vein embolization (PVE) or ligation (PVL), in the setting of 1-stage or 2-stage liver resections, is nowadays considered the standard of care for patients with locally advanced liver tumors and small FLR.2,5-8 However, the need for long intervals between interventions (6-12 weeks), results in resectability rates that rarely exceed 60-80%. In 2012, Schnitbauer et al introduced a novel 2-stage technique that allowed tumor resection in 25 patients from 5 German centers with marginally resectable or primarily nonresectable disease by means of a rapid and large FLR hypertrophy. This technique was later popularized with the acronym ALPPS for Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy. The promising preliminary results obtained with this new surgical proposal in terms of hypertrophy and the possibility of challenging the previous methods generated a pronounced reaction in the surgical community world-wide that has rarely been seen in the history of hepato-pancreato-biliary (HPB) surgery. However, the possibility of achieving a short-term hypertrophy and high resectability rates has been counteracted in most published series by an increased risk of morbidity and mortality. The aim of this study was to evaluate the results with the ALPPS procedure in a single high-volume HPB center, with special emphasis in the safety and feasibility of this new 2-stage strategy. Data for all patients undergoing 2-stage hepatectomies with the ALPPS approach at the HPB Surgery Section of the Hospital Italiano de Buenos Aires between June 2011 and April 2014 was analyzed on an intention to treat basis. Patient demographics, clinical characteristics (body mass index, anesthesiological risk score, Charlson comorbidity index, preoperative chemotherapy), tumor type, surgical details, FLR hypertrophy, postoperative liver function, postoperative complications, length of hospital stay and survival were analyzed. Regarding the surgical procedure, during the first stage a complete tumor resection (clean-up) of the FLR is performed if bilateral disease was present, either trough anatomical or atypical resections. Subsequently, the portal vein of the diseased hemi-liver (DH) is divided and either total (up to the inferior vena cava) or partial (up to the middle hepatic vein) parenchymal transection using the Cavitron Ultrasonic Surgical Aspirator (CUSA; Valley Lab, Boulder, CO, USA) is carried out. At the end of the first stage, the DH is either wrapped in a plastic bag or a plastic sheath placed between the cut surfaces. Once volumetric CT analysis demonstrated enough FLR hypertrophy and provided the patient is in good condition, the second stage is carried out the next available operative day resecting the DH. The type of liver resections performed were defined using the Brisbane 2000 nomenclature.

Official Title
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Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy (ALPPS): Safety, Feasibility and Efficacy at a Single Center

Conditions
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Locally Advanced Malignant Liver Disease

Intervention / Treatment
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* Procedure: ALPPS


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with marginally resectable or primarily non-resectable locally advanced liver tumors Insufficient FLR either in volume or quality Exclusion Criteria: Unresectable liver metastases in the future liver remnant or unresectable extrahepatic metastases Severe portal hypertension High anesthesiological risk Unresectable primary tumor

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| ALPPS group<br>Patients with small future liver remnant who are operated with the Associating Liver Partition and Portal vein ligation for Staged hepatectomy approach | Procedure: ALPPS<br>* Associating Liver Partition and Portal vein ligation for Staged hepatectomy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety of the procedure defined as the incidence of postoperative complications and mortality | Ocurrence of any postoperative complication or mortality considering the Dindo-Clavien classification of surgical complications | within the first 90 days after the first stage | 
| Feasibility of the procedure defined as percentage of patients that complete both surgical stages. | Percentage of patients that finally arrive to the 2nd stage of the ALPPS approach | within 4 months after the first stage | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy of the procedure defiend as the percentage of patients who achieve a sufficient future liver remnant hypertrophy | Achievement of sufficient short-term hypertrophy of the future liver remnant (FLR). Sufficiency was defined as a FLR >0.5% of body weight or >25% of standardized total liver volume in case of healthy liver parenchyma, or >0.8% and 40% in case of diseased parenchyma. | within 10 days after the first stage | 
| Disease-free survival and overall survival | Disease free survival was the time that a patient remained alive and without evidence of disease from the second stage. Overall survival was the time from the first stage to patient death. | 1 and 2 years | 
| Risk factors for morbidity | To identify clinical or operative risk factors of postoperative complications | within 3 month after the first stage | 
| Risk factors for a reduced kinetic growth rate of the future liver remnant (<35 cc/day) | To identify clinical or operative risk factors or a reduced kinetic growth rate of the future liver remnant (<35 cc/day) | within 3 months after the first stage | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Liver tumor, ALPPS, Two-stage hepatectomy, Morbidity, Hypertrophy