ALPPS: two-stage hepatectomy

ALPPS is a two-stage surgical strategy that can be used when an extensive liver resection would initially leave an insufficient residual liver, that is, a liver that is too small or has limited functional capacity to perform the organ’s functions.

The first operation promotes the growth of the liver to be preserved, and the second completes the resection once tests confirm that the remaining liver has reached an adequate volume and function.

What is ALPPS?

Some liver tumours require the removal of a considerable amount of tissue to achieve a complete resection. Before surgery of this magnitude, the team calculates how much liver will remain after the operation and assesses whether that portion will be able to adequately maintain the necessary functions.

When the remaining liver tissue is initially deemed insufficient, various strategies can be used to stimulate its growth before the resection is completed. ALPPS divides this process into two closely related procedures.

During the first procedure, the flow in the portal vein—the vessel that carries most of the blood from the digestive system to the liver—is modified, and the tissue to be preserved is partially or completely separated from the portion to be removed later. These manoeuvres provide a powerful growth stimulus to the future residual liver.

Between the two operations, the volume and function of the liver are assessed, and the patient’s overall recovery is evaluated. When progress is satisfactory, the second procedure is carried out and the hepatectomy is completed, that is, the resection of the previously planned portion of the liver.

The future residual liver

The future residual liver is the part of the liver that will remain after resection. Its ability to maintain the organ’s functions is one of the key factors in deciding whether an extensive hepatectomy can be performed with an adequate safety margin.

This assessment goes beyond mere size. It also matters how effectively that tissue actually functions and what its quality is. The presence of cirrhosis, fibrosis, fat accumulation (steatosis), difficulty in bile drainage (cholestasis) or certain previous systemic treatments can reduce its functional capacity.

For this reason, a residual liver that appears sufficient on a CT scan may not necessarily offer the same functional capacity as a healthy liver. Similarly, the rapid increase in volume that may occur after the first stage of ALPPS does not imply that liver function will increase at exactly the same rate.

Planning therefore combines anatomical, clinical and functional information. No single measurement on its own can describe how the liver will respond following an extensive resection.

Why is it carried out in two stages?

The purpose of dividing the procedure into two stages is to allow the remaining liver to grow before the affected part is permanently removed. In this way, the first operation creates the conditions for increasing the future residual liver volume, and the second completes the resection once an adequate response has been confirmed.

Hypertrophy — the enlargement of liver tissue — tends to occur more rapidly with ALPPS than with some preparatory strategies based solely on modifying portal flow. However, anatomical growth is only one part of the assessment: sufficient liver function and appropriate clinical conditions must also be restored.

The second stage is considered once the team confirms that the future remnant has reached an adequate volume, is functioning satisfactorily and the patient has recovered from the first operation. They also check that there are no significant complications and that completing the resection continues to offer a reasonable prospect of benefit.

Indications

The most extensive clinical experience with ALPPS relates to certain liver metastases from colorectal cancer, particularly where both lobes of the liver are affected and conventional resection would leave an insufficient residual tumour.

In carefully selected patients, this strategy may increase the likelihood of achieving a complete resection. When considering this approach, the team must assess whether all visible disease can be removed, evaluate the response to previous treatments, and confirm that the tumour’s progression continues to justify a procedure of this magnitude.

In hepatocellular carcinoma, ALPPS may be considered in exceptional cases. In these patients, the quality of the liver tissue and the possible presence of cirrhosis, fibrosis or portal hypertension are of particular importance, as these can limit both the growth and the functional capacity of the residual liver.

It has also been used selectively in some extensive intrahepatic cholangiocarcinomas. The situation is particularly complex in perihilar cholangiocarcinoma, where cholestasis, the risk of biliary infection and the possible need for vascular and biliary resections add to the difficulty and risk of the procedure.

In other primary or secondary liver tumours, its use is usually restricted to rare situations requiring individual assessment by teams with specific expertise in hepatobiliopancreatic surgery.

Selection and treatment planning

The decision to carry out ALPPS begins with determining whether there is a reasonable chance of completely removing the tumour whilst preserving a sufficient amount of functional liver tissue.

The assessment examines the distribution of the lesions, their relationship with blood vessels and bile ducts and, where prior oncological treatment has been undertaken, the response achieved. The possible presence of disease outside the liver and the biological behaviour of the tumour are also assessed, as the rate at which the residual tumour may grow is only relevant if completing the resection continues to make oncological sense.

The volume and function of the future residual liver, the quality of the liver tissue, the patient’s age, general condition and nutritional status are then assessed. Cardiac, respiratory and renal function are also part of the assessment, as the strategy involves undergoing two related surgical procedures within a relatively short period of time.

ALPPS may be particularly relevant when rapid growth of the residual lobe is required, or when other strategies have failed to achieve the conditions necessary for resection. The final decision must take into account its potential benefits, the complexity of the procedure and the alternatives available for each individual case.

Tests to assess the liver and plan surgery

Planning usually involves a high-quality CT scan or MRI. These scans enable the distribution of lesions to be mapped out and the anatomy of the blood vessels and bile ducts to be studied, as well as calculating how much of the liver will remain after resection.

Liver volumetry uses radiological images to calculate the volume of the future residual lobe. Where available and appropriate, liver function tests provide additional information on the actual capacity of that part of the organ.

Blood tests enable the assessment of, amongst other parameters, bilirubin, coagulation, liver enzymes and kidney function. This functional assessment is particularly important in cases of cirrhosis, cholestasis, steatosis or prolonged exposure to certain systemic treatments.

All this information is integrated with the oncological assessment to confirm that the disease remains amenable to complete resection. In a strategy of this complexity, the decision-making process benefits from a multidisciplinary assessment involving specialists with specific expertise in liver surgery.

First stage of the procedure

The first operation is carried out under general anaesthesia. At the start of the surgery, the team reassesses the extent of the disease and confirms that the planned surgical approach remains viable.

Where there are lesions in the part of the liver to be preserved, some may be treated during this first stage, provided that an adequate functional remnant can be preserved.

The blood flow in the branch of the portal vein supplying the area to be resected is then interrupted. As a result, a greater proportion of the portal flow is directed towards the future remnant, helping to stimulate its growth.

The next part of the procedure involves performing a partial or complete division of the liver tissue separating the future remnant from the area to be removed. The portion with the highest tumour burden remains temporarily in the abdomen and retains its arterial blood supply until the second stage.

Before the operation is completed, bleeding is controlled and the site is checked for any bile leaks. A period of close monitoring then begins to assess how the future remnant responds and how the patient progresses after surgery.

Assessment between the two interventions

The period between the two stages is usually relatively short, but the decision to proceed does not depend on a fixed number of days.

During this interval, the necessary tests are repeated to measure the growth of the future remnant and assess its function. Coagulation, liver function tests and clinical progress are also reviewed, along with the possible occurrence of infections, bile leaks, abdominal collections or other complications.

Based on this information, the team decides when conditions are suitable for completing the resection. If the remnant requires more time to achieve the necessary volume or function, the second operation may be postponed. Clinical and oncological progress also form part of this decision.

Second stage of the procedure

Once the remaining liver is deemed sufficient and the patient’s clinical progress is favourable, a second operation is carried out to complete the hepatectomy. During this operation, the blood vessels, bile ducts and structures connecting the part of the liver to be resected are severed. That portion is then removed.

Before the procedure is completed, checks are carried out to ensure that the remaining liver is receiving adequate blood flow, that venous drainage is functioning correctly and that bile is draining safely.

Following the operation, monitoring focuses particularly on liver function, coagulation, bleeding, infections and any possible bile leaks.

Variants of ALPPS

Since the procedure was first described, modifications have been developed with the aim of reducing the surgical impact of the first stage whilst maintaining the necessary stimulation for the growth of the future remnant.

These include partial ALPPS, mini-ALPPS and certain laparoscopic, robotic or energy-assisted approaches. These variants modify different aspects of the partitioning or surgical access with the aim of reducing surgical trauma, adhesions and certain complications.

Not all of them are supported by the same level of evidence, nor are they suitable for every anatomy or tumour type. The choice depends on the characteristics of the disease, the quality of the liver and the experience of the surgical team.

Benefits and objectives

The main objective of ALPPS is to achieve rapid growth of the remaining liver tissue, thereby enabling the completion of a resection that could not initially be carried out with a sufficient functional volume of liver.

The most robust comparative evidence comes from selected patients with liver metastases from colorectal cancer. In this context, the technique has enabled resection to be completed more frequently than certain conventional two-stage strategies.

The relatively short interval between the two procedures may reduce the period during which the disease could progress prior to the definitive resection. The final outcome depends, however, on the residual liver achieving adequate function, the second procedure being feasible, and it being possible to remove all the targeted tumour.

When the aim of surgery is curative, ALPPS can form part of a strategy designed to achieve complete resection. As with other cancer treatments, this therapeutic intention does not allow for an individual prediction of the likelihood of subsequent recurrence.

Risks and possible complications

ALPPS comprises two highly complex liver procedures, each of which carries specific risks.

Following the first stage, bleeding, infection, abdominal fluid collections, bile leaks or thrombosis may occur. The development of the remaining liver is also a key factor: it may grow less than anticipated or increase in volume without yet achieving sufficient functional capacity.

Following completion of the resection, one of the most significant complications is post-hepatectomy liver failure, which occurs when the remaining liver is unable to adequately maintain the functions required by the body. Haemorrhage, sepsis, coagulation disorders, renal failure, bile leaks, and respiratory or cardiovascular complications may also occur.

The likelihood and type of complications depend on multiple factors, including the quality and function of the liver tissue, the presence of cirrhosis or cholestasis, and the complexity of any vascular or biliary resections that may be required.

Advances in the technique, more precise selection of candidates and modifications to the procedure have led to improved outcomes compared with early experiences. Nevertheless, ALPPS remains a highly complex surgical strategy that requires particularly careful indication.

Recovery and follow-up

Recovery comprises two interconnected post-operative periods. Following the first operation, pain, bleeding, liver function and the possible onset of infections or bile leaks are monitored. At the same time, the necessary tests are carried out to assess the growth and function of the future remnant and to determine when the second stage can be considered.

The care pathway may vary depending on the patient’s clinical progress. Some patients remain in hospital during the interval between the two procedures, whilst in other situations the follow-up arrangements may be adapted to the patient’s condition and the centre’s protocol.

After the hepatectomy is complete, monitoring focuses particularly on liver function, coagulation, kidney function, breathing and digestive recovery. Diet and physical activity are gradually reintroduced.

In the weeks that follow, fatigue, reduced physical strength or a loss of appetite may persist. Depending on the individual’s needs, recovery may include nutritional support and rehabilitation.

When ALPPS forms part of cancer treatment, subsequent follow-up is integrated into the oncological strategy. The need for additional systemic treatments depends on the type of tumour, the results of the histopathological analysis of the surgical specimen, clinical progression and any previous therapies received.

Treatment options

The decision to proceed with ALPPS is made after comparing the various options capable of increasing the future residual liver volume or allowing liver resection whilst preserving as much functional tissue as possible.

One such option is portal embolisation, an interventional radiology procedure that blocks the branches of the portal vein corresponding to the part of the liver that is to be removed. By redirecting portal blood flow towards the future residual lobe, it stimulates its growth without the need for an initial liver operation.

Hepatic venous deprivation combines portal embolisation with the occlusion of one or more hepatic veins. Its aim is to achieve a more intense growth stimulus whilst maintaining an initial stage carried out using interventional techniques.

In certain situations, a conventional two-stage hepatectomy, resections that preserve a greater amount of parenchyma — the functional tissue of the liver —, the ablation of certain lesions, or systemic treatment followed by a further surgical assessment may also be considered.

The comparison between these strategies is not limited to determining which one produces the most rapid hypertrophy. The team also assesses the initial impact of each procedure, the time required until resection, the function the remaining liver is expected to achieve, the characteristics of the tumour, and the actual likelihood of completing the planned treatment.

Specialists involved

Treatment using ALPPS requires particularly coordinated planning, as the decision does not depend solely on the technical feasibility of performing the two procedures. It is necessary to assess, taken together, the extent of the tumour, the likelihood of achieving a complete resection, the amount and function of the liver to be preserved, and the patient’s overall condition.

Oncological Surgery forms the surgical backbone of this care pathway. Within this department, the Hepatic Oncology Surgery Unit is specifically dedicated to the assessment and surgical treatment of primary and secondary liver tumours. Its role begins with the assessment of resectability — the possibility of removing all the anticipated tumour whilst preserving a functional liver — and continues with the planning of the two stages of the ALPPS procedure and the assessment of the future residual liver.

The oncological strategy is coordinated with Medical Oncology. In cases of colorectal cancer, liver tumours or bile duct tumours, the Digestive Tumours Unit may be specifically involved. These specialists assess the biology and extent of the disease, the response to previous systemic treatments, and the need to incorporate chemotherapy, targeted therapies or other treatments before or after surgery.

Anatomical and functional planning is supported by Diagnostic Imaging. Computed tomography, magnetic resonance imaging and volumetric studies provide information on the distribution of lesions, their relationship with blood vessels and bile ducts, and enable the calculation of how much liver will remain after resection.

Interventional radiology takes on particular importance when comparing ALPPS with other strategies aimed at increasing the future residual liver volume, such as portal embolisation or hepatic venous deprivation. Their involvement enables an assessment of whether an interventional technique might offer a suitable alternative before opting for a two-stage surgical strategy.

Prior to each procedure, the Department of Anaesthetology and Resuscitation assesses the perioperative risk and plans the anaesthetic management for highly complex liver surgery. Following the operation, the Intensive Care Unit may become involved when the patient’s clinical condition requires advanced monitoring or vital sign support during the post-operative period.

Analysis of the surgical specimen by the Department of Pathology enables the tumour to be fully characterised and provides relevant information for subsequent oncological decisions. Where the patient’s nutritional status or recovery so requires, specialists from Endocrinology and Nutrition, Nursing and other support teams may also be involved.

Not everyone requires the involvement of all these specialists at every stage. The care pathway is tailored to the disease, the function of the remaining liver, the complexity of the surgery and the patient’s progress between the two procedures, whilst maintaining coordination amongst the various departments involved.

When to seek medical advice following surgery

Following either procedure, follow-up care enables your recovery to be monitored and any potential complications to be detected at an early stage. You should contact the healthcare team if you experience a fever, progressively worsening abdominal pain, persistent vomiting, abdominal distension or significant difficulty in maintaining an adequate diet and fluid intake.

The appearance of yellowing of the skin or eyes, very dark urine, a marked reduction in urine output, drowsiness or confusion, bleeding, significant changes to the surgical wound or breathing difficulties also require assessment.

Severe pain, loss of consciousness, heavy bleeding, severe breathing difficulties or rapid deterioration in your general condition require urgent medical attention.

Medical information for general guidance

This information sheet aims to explain what ALPPS is, why a liver resection can be divided into two stages, how the remaining liver is assessed, what happens during each procedure, and how the decision is made as to when the surgery can be completed. It also summarises the main indications, alternatives, risks, and the recovery and follow-up process.

At the Publio Cordón Memorial Hospital, we believe it is important for medical information to be accurate, understandable and useful in guiding each person through their care journey. Our specialists devote part of their work to explaining conditions, tests and treatment options in an accessible way, helping patients and their families to better understand each stage and participate with greater confidence in decisions about their health. This commitment to knowledge and public outreach is also part of our commitment to research and the advancement of medicine.

The information provided here outlines the general principles of ALPPS and does not, on its own, determine whether this strategy is suitable for a specific individual. The indication depends, amongst other factors, on the type and extent of the disease, the feasibility of performing a complete resection, the volume and function of the future residual liver, the patient’s general condition and the available alternatives. These circumstances must be assessed on a case-by-case basis by a team with experience in complex liver surgery.