Review article: Biomedical intelligence

Multimodal treatment strategies for colorectal liver metastases

Publication Date: 15.02.2021
Swiss Med Wkly. 2021;151:w20390

Birrer Dominique Lisaa, Tschuor Christopha, Reiner Cäcilia S.c, Fritsch Ralphb, Pfammatter Thomasc, Schüler Helena Garciad, Pavic Matead, De Oliveira Michellea, Petrowsky Henrika, Dutkowski Philipa, Oberkofler Christian E.a, Clavien Pierre-Alaina

a Department of Surgery, Swiss Hepato-pancreato-biliary and Transplantation Centre, University Hospital Zurich, Switzerland

b Department of Medical Oncology and Haematology, University Hospital Zurich, Switzerland

c Institut für Diagnostische und Interventionelle Radiologie, University Hospital Zurich, Switzerland

d Department of Radiation Oncology, University Hospital Zurich Switzerland


Colorectal cancer is the third most common cancer worldwide. Half of CRC patients develop liver metastases during the course of the disease, with a 5-year survival rate close to zero in the absence of therapy. Surgical resection remains the only possible curative option, and current guidelines recommend adjuvant chemotherapy, resulting in a 5-year survival rate exceeding 50%. Neoadjuvant systemic therapy is not indicated in cases with simple resection but should be offered to all patients with extensive bilobar disease. Personalised systemic treatment is essential to convert upfront non-resectable lesions to resectable ones. Anatomical resections, non-anatomical resections and two-stage hepatectomies can be performed though open or minimally invasive (laparoscopic or robotic) surgery.

The extent of a hepatic resection is limited by the risk of postoperative liver failure due to a too small liver remnant, inflow or outflow obstruction or insufficient biliary drainage. About 75% of patients are diagnosed with non-resectable liver metastases not amenable to a standard upfront resection. In recent years, effective therapeutic approaches have revolutionised liver surgery and new strategies have enabled the conversion of primarily non-resectable metastatic disease for resection. These strategies include oncological and surgical therapies, as well as combinations of the two. From an oncological perspective, colorectal liver metastases may be treated by systemic chemotherapy or immunotherapy, or selective intra-hepatic arterial infusion chemotherapy, depending on the extent of the disease and the mutational status. In surgery, we often apply two-stage strategies using portal vein occlusion, such as portal vein embolisation or ligation, or complex two-stage hepatectomy such as associating liver partition and portal vein ligation for staged hepatectomy. Other additive tools to reach curative resection are tumour ablations (electroporation, microwave or radiofrequency). The role of stereotactic radiation of liver metastases is not yet well defined. Modern radiation techniques, including image guidance, breath hold and gating, were only introduced for a larger patient population in recent years. Therefore, prospective studies with larger patient cohorts are still pending.

Over the last decade, liver transplantation has gained increasing attention in selective cases of non-resectable colorectal liver metastases, with promising cohort studies, but definitive recommendations must await the results of ongoing randomised controlled trials.

The optimal treatment of patients with colorectal liver metastases requires the timely association of various strategies, and all cases must be discussed at multidisciplinary team conferences. While colorectal liver metastases was a uniformly lethal condition a few decades ago, it has become amenable to curative therapies, with excellent quality of life in many scenarios. This review reports on up-to-date treatment modalities and their combinations in the treatment algorithm of colorectal liver metastases.

Keywords: colorectal liver metastases, CRLM, ALPPS, associating liver partition and portal vein ligation for staged hepatectomy, portal vein embolisation, PVE, portal vein ligation, PVL


In Switzerland, the age-standardised* incidence of new cases of colon cancer between the years 2012-2016 was 45.8 for men and 29.7 for women. Compared to their age group, women with colon cancer are 9.7 times and men 15.9 times more likely to die, making it the third most common cause of cancer death in both sexes. (* The age-standardised incidence indicates the disease rate in a specific time period which would be expected in the considered population if its age structure agreed with that of the standard population. † Standardised mortality rate per 100,000 inhabitants, European standard) [1].

Worldwide, an estimated 1.4 million new colorectal cancer (CRC) cases are diagnosed every year, with 700,000 cancer deaths [2]. In 30–50% of patients with CRC the liver is the predominant site for metastases, due to its immediate drainage from the gastrointestinal tract [36]. Half of CRC patients are diagnosed with synchronous liver metastases [4, 7]. Without treatment the prognosis is dismal, with a 5-year survival rate of close to zero in historical data [8, 9]. Surgical resection of the metastatic tumours is the only curative treatment with a 5-year survival rate currently exceeding 50% in most series [10, 11]. Unfortunately, only 25% of patients with colorectal liver metastases (CRLM) qualify for resection at initial presentation. An increasing number of patients may benefit from down-staging strategies and eventually from a curative resection, often followed by encouraging long-term outcomes. Combinations of systemic chemotherapy and immunotherapy lead to current response rates of over 50% for down-staging [12].

The combination of multimodal surgical and non-surgical therapies offers the best chance for cure in patients with CRLM. In this review, we present up-to-date, personalised treatment options for the management of CRLM as practiced in our hepato-pancreato-biliary (HPB) centre in Zurich (fig. 1)

Figure 1
Flow chart of the treatment algorithm for colorectal metastases at the Swiss HPB Centre, Zurich, Switzerland.
ALPPS = associating liver partition and portal vein ligation for staged hepatectomy; TSH = classical two-stage hepatectomy; BSC = best supportive care; FLR = future liver remnant; OLT = orthotopic liver transplantation; PVE = portal vein embolisation.

Diagnostic work-up of colorectal liver metastases

  • Thoraco-abdominal computed tomography (CT) is part of the standard imaging work-up.
  • Magnetic resonance imaging (MRI) of the liver with hepatobiliary contrast media shows the highest sensitivity for CRLM.
  • Positron emission tomography (PET)-CT can change surgical management by detecting extrahepatic metastases.

Medical history with physical examination, laboratory tests including carcinoembryonic antigen, and abdomen ultrasound or a CT scan are usually available at the time of referral to the surgeon. In our hepato-pancreato-biliary centre in Zurich, Switzerland, we favour MRI of the liver with hepatobiliary contrast media (Primovist, Bayer Healthcare) to better detect liver metastases and surgically relevant liver structures [13]. MRI with hepatobiliary contrast media shows the highest sensitivity for liver metastases compared to contrast-enhanced CT or PET-CT, especially for lesions <1 cm and in patients who have undergone chemotherapy [13, 14].

If the lesions appear resectable, PET-CT is performed to detect extrahepatic disease [15]. The CT scan is crucial for detecting pulmonary metastases. Lymph node metastases and malignant disease in other organs may also be identified more easily with PET-CT [15]. With the use of additional PET-CT in patients with resectable CRLM based on CT scans, surgical management is changed in 10% of patients and the rate of futile laparotomies can be reduced [15].

Assessment of liver function

  • Testing liver function prior to extended liver surgery, including with bilirubin, factor V, international normalised ratio and albumin tests, is recommended.
  • Assessment of global liver function includes indocyanine green and hepatobiliary iminodiacetic acid testing.

Postoperative outcomes mainly depend on the size and quality of the future liver remnant (FLR).

A preoperative assessment of the liver for volume and function is important in order to predict the risk of post-hepatectomy liver failure. Assessing and quantifying liver function before surgery is still controversial because no single physiologic marker or score alone predicts postoperative liver failure.

There are three types of liver function tests: conventional liver function tests, scoring systems and quantitative tests [14]. The most widely used conventional liver function test in clinical practice is assessment of the laboratory values, including serum bilirubin, factor V and Quick test. The Child-Pugh score, which was designed to assess the risk of death in cirrhotic patients undergoing surgery for portal hypertension, remains one of the most popular scoring systems [16, 17]. This score applies only to patients with cirrhosis. Patients with Child-Pugh score A usually have a favourable course, while Child-Pugh score C represents a contraindication for surgery. Surgery in Child-Pugh score B cirrhotic patients must be discussed case by case.

Among the quantitative tests, the indocyanine green test is correlated with liver function and the regenerative capacity of the liver [1820]. This is a simple, non-invasive test that can be performed at the bedside. Indocyanine green test is a water-soluble dye that is injected via a peripheral venous access. It binds to proteins, and after being taken up by hepatocytes, is excreted into the bile. The plasma disappearance rate and the retention rate at 15 minutes are measured by pulse spectrophotometry [21]. Plasma disappearance rate values between 18% and 24% and a retention rate at 15 minutes <15% may be indicators for normal liver capacity and low-risk liver resection. Nevertheless, since indocyanine green testing depends on the hepatocyte uptake as well as excretion via the bile, chronic or acute liver diseases may influence indocyanine green test results, limiting their predictive value [2126].

The LiMAx test is another method for investigating liver function at the bedside. It is based on the assessment of 13C-methacetin metabolism by the liver-specific cytochrome P450 1A2 system. 13C-methacetin is administered intravenously and the ratio of 12CO2 to the metabolised 13CO2 is measured by mask breathing. The maximum liver function capacity is defined as the maximum value of the substrate conversion normalised to body weight. A normal liver function is defined as ≥315 μg/kg/h. Values between 140 and 315 μg/kg/h show limited hepatic impairment, while 0–140 μg/kg/h means significant hepatic injury. Preoperative performance in the LiMAx test can help to determine the correct timing of hepatectomy after previous chemotherapy, surgery or portal vein manipulation, preventing post-hepatectomy liver failure [27]. However, both the indocyanine green and LiMAx tests assess only global liver function, and not the function of the FLR specifically.

Exact FLR function can, however, be assessed with a hepatobiliary iminodiacetic acid scan. This is an imaging modality used to investigate metabolic diseases of the liver, as well as excretion dynamics of the gallbladder and bile ducts. A radioactive tracer is injected, taken up by the bile-producing cells and excreted into the biliary tree, which drains into the duodenum. Imaging is obtained by a γ camera and shows liver function for the whole liver as well as for regions or parts of interest, such as the FLR [28].

Quantitative tests evaluate the metabolism and the clearance of different substrates that are mostly or entirely cleared by the liver. It is important to note that quantitative tests provide more reliable information on the preoperative liver function than on the postoperative liver function because they address one of the liver’s true processes (i.e., galactose elimination or bile acid clearance). While in patients with normal liver function the suggested limits for safe resection range from 20 to 30% FLR volume, most guidelines indicate 30% [10, 29].

Perioperative systemic chemotherapy for colorectal liver metastases

  • Down-staging of non-resectable CRLM can be achieved with personalised systemic chemotherapy.
  • Perioperative chemotherapy for resectable CRLM must be restricted to situations with an unfavourable risk profile.

Systemic chemotherapy is an integral part of the multimodal management of CRLM. Perioperative chemotherapy targets micro-metastatic disease in order to reduce the risk of recurrence following resection. In more advanced situations, preoperative chemotherapy aims to convert upfront non-resectable CRLM to resectable ones. Modern personalised combination chemotherapy for metastatic CRC has improved substantially, with current response rates of over 50%, up from approximately 10% with a single-agent treatment prior to 2000.

Upfront resectable CRLM with a favourable risk profile must undergo upfront resection followed by adjuvant chemotherapy, particularly when the patient has not received any previous adjuvant treatment [12]. In less favourable risk constellations, such as with synchronous metastases or a short interval between primary tumour resection and systemic tumour recurrence, perioperative treatment with 6 months of FOLFOX (leucovorin, fluorouracil, oxaliplatin) or CAPOX (capecitabine, oxaliplatin) split evenly before and after surgery, based on the pivotal EPOC trial, is a widely used option [30]. Median overall survival improved from 47 months in the surgery only group to 62 months when adjuvant chemotherapy followed the surgery [31].

In patients with technically non-resectable CRLM, chemotherapy aiming to render them resectable prior to surgery is essential. Conversion treatment aims for maximum tumour shrinkage and typically involves combinations of chemotherapy doublets or triplets with monoclonal antibodies (anti-endothelial growth factor receptor [anti-EGFR], anti-vascular endothelial growth factor [anti-VEGF]). Treatment is personalised, based on molecular profile and biological criteria, most prominently primary tumour sidedness [10]. Reported success rates of conversion treatment are as high as 30% [9, 10]. The optimal duration of conversion therapy has not been established; maximum tumour shrinkage in metastatic CRC is typically achieved after 12–16 weeks of chemotherapy. In these situations, accumulation of toxicity in the liver due to prolonged application of intensified chemotherapy protocols poses a significant risk. It is important to note that modern perioperative treatment, as an essential part of multimodality treatment of CRLM, must be personalised: guided by established principles but highly adaptable to individual constellations.

Molecular subtyping of metastatic CRC is evolving. At least seven clinically relevant subgroups of metastatic CRC exist in clinical routine and impact on perioperative conversion treatment [10]. CRLM from left-sided wild-type tumours (wild-type = absence of a common driver oncogene alteration such as the KRAS, NRAS and BRAF mutations or HER2/neu amplification) should always be treated with chemotherapy plus anti-EGFR antibodies, while CRLM from right-sided wild-type tumours do not appear to benefit from anti-EGFR and are treated with anti-VEGFR plus chemotherapy. Moreover, CRLM from right-sided primaries are associated with inferior prognosis and show inferior response to conversion treatment compared to CRLM from left-sided primaries. BRAF-V600E mutant metastatic CRC show aggressive biological behaviour and very poor prognosis following liver resection. The highly immunogenic dMMR/MSI-H subgroup show excellent responses to immune checkpoint inhibitors, while HER2-amplified metastatic CRCs show encouraging results with HER2 blocking agents. The largest molecular subgroup of KRAS/NRAS mutant metastatic CRC are resistant to anti-EGFR treatment and are commonly treated with a chemotherapy doublet or triplet anti-VEGF-receptor (bevacizumab) for conversion treatment.

In selected cases, locoregional chemotherapeutic treatment can be combined with systemic treatment to maximise tumour response. Hepatic artery infusion chemotherapy via a pump, combining systemic and locoregional treatment in the preoperative setting, was introduced in 1969. Continuous hepatic artery infusion chemotherapy with floxuridine in combination with systemic chemotherapy has been associated with satisfactory conversion rates in selected cases of non-resectable CRLM [29].

Surgical strategies for synchronous colorectal liver metastases

  • Symptomatic primary tumours in the colon or rectum should be treated first with high priority.
  • In asymptomatic primary CRC, the liver first approach is preferred.

Several surgical strategies may be considered to address synchronous CRLM. (1) The classic approach is to treat the primary colon or rectum tumour first followed by the liver metastasis in a second step, in combination with variable applications of perioperative chemotherapy. This strategy remains the gold standard in patients with symptomatic primary tumours. (2) Simultaneous resection combining resection of the primary tumour and the liver metastases. This one-step procedure is feasible and has been reported with success in many articles, usually in cases with minimal liver involvement (e.g., <3 segments) [32, 33]. This method can often be done with a minimal invasive approach (laparoscopic, robotic) [33]. (3) The “liver first approach” involves resecting the CRLM upfront and is routinely associated with neoadjuvant chemotherapy [10]. It is the preferred approach at our hepato-pancreato-biliary centre in Zurich, where we often deal with major spread of the liver tumour. We often start with systemic chemotherapy over 3 months, followed by restaging and, in the case of tumour response, eventually a two-stage hepatectomy. A few weeks later, the excision of the primary colon tumour completes the complete removal of tumour disease [10, 29, 34].

Convincing data on survival advantages between colon first and liver first strategies are lacking [32]. In the context of hepatic resections, anatomical resections are defined as resections of one or more anatomic liver segments [35]. For example, a right hemi-hepatectomy involves the resection of segments V to VIII. Non-anatomical resections, also named parenchymal-sparing hepatectomies, aim to achieve oncological resections with a minimum sufficient margin while preserving as much liver parenchyma as possible. It has been suggested that a 1-mm oncological margin is sufficient in CRLM [36]. In our centre, we accept only resection with a 0.5-cm tumour-free margin, which we achieve, when necessary, with additional application of radiofrequency on the margin (e.g., Aquamantys, Medtronics) [37].

Strategies to increase the future liver remnant

  • Two-stage hepatectomy is recommended if the FLR is less than 25–30%.
  • A larger FLR might be required in injured liver parenchyma.
  • Strategies to increase the FLR are based mainly on occlusion of the portal vein.

A number of strategies have been developed to increase the FLR. (fig. 2, fig. 3c–h). The first human application of such a strategy, portal vein ligation of the tumour-bearing lobe during surgery, was described in 1975 [38]. Portal vein ligation was thought to induce tumour regression in the affected lobe. But portal vein occlusion of one liver lobe leads to compensatory hypertrophy of the contralateral, non-occluded FLR, which may ultimately enable surgery in cases where the FLR does not yet have the necessary volume/function to allow resection of the diseased part of the liver [38, 39].

Figure 2
Treatment algorithm for an individual patient with bilobar colorectal liver metastasis at the Swiss HPB Centre, Zurich, Switzerland. (a) Start of chemotherapy. (b–d) MRI (Primovist) global reduction of all lesions. Lesion: 22.4 cm3, FLR right liver: 58.69% / 742 cm3. (e) Intraoperative situs ALPPS Stage I. (f) MRI (Primovist) one week after Stage I: clean FLR (right lobe) with 901 cm3 and adequate compensatory overgrowth before Stage II. g) Intraoperative situs ALLPS Stage II. (h) Anatomical specimen after hepatectomy. (i–k) 6 months after surgery, CRLM reappears. (l) hypervascucularised CRLM poor in contrast with selective probing of the right hepatic artery with a 2.7F catheter. Selective internal radiation therapy (SIRT) for recurrent lesion after 7 months.
Figure 3
Strategies to increase the future liver remnant. (a) Parenchyma with bilobar CRLM before wedge resections (b) After wedge resections of small peripheral CRLM (c) One-stage liver surgery with portal vein embolisation on the lobe to be removed. (d) Hypertrophy of the FLR. (e) Removal of the embolised right lobe. (f) Bilobar CRLM before surgery g) Open ligation on the right portal vein branch and cleaning of the FLR. (h) Removal of the deportalised lobe. Illustration: Carol De Simio-Hilton.

In a classical two-stage procedure, the portal branch to the diseased liver lobe is ligated intra-operatively and the resection can be performed at a later stage, when the FLR has reached its necessary volume. Nevertheless, this might take several weeks and the waiting time cannot be justified for certain tumour growth patterns. Therefore, a concept termed associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) was introduced by a group from Regensburg, Germany in 2007. ALPPS is a combination of portal vein ligation and in-situ liver parenchyma transection performed during the first stage. Initial experience suggested that ALPPS leads to faster liver regeneration (7–10 days) compared to portal vein embolisation or ligation (4–12 weeks) (fig. 2, fig. 3f–h) [38]. The mechanisms behind this enhanced stimulation and accelerated regenerative response of the liver after parenchymal liver transection combined with portal vein ligation are currently being investigated extensively [40]. Advances in patient selection and in modalities to assess liver function, as well as modifications to the ALPPS technique, have led to a significant decrease in morbidity and mortality in patients undergoing ALPPS [4144]. Morbidity and mortality for ALPPS are currently comparable with conventional major hepatectomy procedures [45].

Laparoscopic and robotic liver surgery for colorectal liver metastases

  • Laparoscopic liver resection for CRLM is associated with significantly fewer postoperative complications compared to open surgery.
  • Laparoscopic liver resection is cost-effective and oncologically adequate.
  • Robotic technology is currently used for minor as well as major liver surgeries, including ALPPS, and may rapidly become the standard approach.

Minimally invasive resection of CRLM with a laparoscopic or robotic approach is gaining increasing acceptance, supported by proven short-term postoperative benefits [46] and reported equal oncologic outcomes compared to open surgery. The first randomised controlled trial for open vs laparoscopic liver surgery, from Norway (COMET trial), showed that laparoscopic liver resection for CRLM is associated with significantly fewer postoperative complications compared to open surgery [47]. Moreover, a subgroup analysis of patients undergoing laparoscopic resection of CRLM located in the postero-superior segments (difficult access by any approach) revealed a shorter hospital stay and similar perioperative outcomes compared to open resection [48]. Data accumulated into a large cohort of patients from expert centres showed that laparoscopic liver resection is cost-effective [46, 47, 49, 50]. The ORANGE II PLUS trial, currently recruiting patients, will be the first randomised, multicentre study to compare open vs. laparoscopic hemi-hepatectomy. At our hepato-pancreato-biliary centre, we currently favour robot-assisted liver resection, particularly for tumours located in the difficult right posterior liver segments. Robotic surgery offers a better degree of freedom in moving the instruments, better vision and better precision [51]. Exponential growth of the use of minimally invasive liver surgery in the past few years mandates the continuous development of necessary guidelines.

Local therapies for non-resectable liver metastases

Ablative therapies

Radiofrequency and microwave ablation are the most frequent ablative thermal modalities (fig. 4). These techniques allow CT- or ultrasound-guided localisation and precise open or percutaneous destruction of central liver tumours close to main structures not accessible for surgery. Microwave ablation induces more coagulation necrosis in a shorter time than radiofrequency ablation. Microwave ablation is nowadays used more frequently as it is more effective when treating a small number of tumours (<5) of limited size (<3 cm), showing low rates of post-interventional complications (1–3%) and excellent local tumour control [52]. However, long-term oncological results for microwave ablation fail to show superiority over surgical resection for small tumours, and have clearly worse outcomes (66% local recurrence rate) for CRLM larger than 3 cm [53]. An ongoing randomised controlled trial from the COLLISION trial group may answer the question of whether or not ablation is inferior to surgery for lesions ≤3 cm. Ablation could be a promising alternative, with reduced morbidity and mortality, a shorter hospital stay and economic benefits. Unfortunately, the applicability of radiofrequency and microwave ablation for tumours close to large vessels is limited due to the “heat sink effect” (fig. 4).

Figure 4
Radiofrequency (RFA) and microwave ablation (MWA) are the most frequently used ablative thermal modalities. Illustration: Carol De Simio-Hilton.

Irreversible electroporation is a newer, non-thermal ablative option to eliminate lesions involving important vascular or biliary structures. Irreversible electroporation does not affect the extracellular matrix and the integrity of the biliary and vascular structures is preserved, enabling cellular recolonisation. However, the high-voltage current pulses used generate excitation of skeletal and cardiac muscle. General anaesthesia with neuromuscular blockade is therefore necessary during the procedure, and cardiac arrhythmia is an absolute contraindication for irreversible electroporation. The exact placement of multiple “soft” probes is challenging and consistently time-consuming [54].

Stereotactic external radiotherapy / stereotactic body radiotherapy

Historically, external beam radiotherapy has played a minor role in the treatment of CRLM because of the low radiation tolerance of the liver [55]. Technological advances in the past few decades have enabled the conformal delivery of high radiation doses to a defined lesion whilst sparing functional liver tissue. Stereotactic body radiotherapy, a form of high-precision radiotherapy in which ablative radiation doses are delivered non-invasively in 1 to 10 ambulatory treatment sessions, was shown to be efficacious, with 2-year local control rates ranging from 59% to 84%, while having a favourable toxicity profile [56, 57]. Notably, most patients offered stereotactic body radiotherapy had serious comorbidities and were considered medically unfit for major liver surgery or had non-resectable metastases. When evaluating the optimal treatment modality for local therapy of non-resectable liver metastases, tumour size is an important factor: subgroup results report higher local control for stereotactic body radiotherapy than for radiofrequency ablation in metastases >2 cm, but not for those ≤2 cm [58]. Accordingly, the European Society for Medical Oncology consensus guidelines propose a “toolbox” concept [12], where stereotactic body radiotherapy should only be considered for patients with a contraindication for or who refuse an invasive procedure, as well as for patients with large liver metastases or metastases located at central biliary or vascular structures. The optimal integration of stereotactic body radiotherapy into modern multimodal treatment concepts remains to be defined. The recent introduction of MRI-guided radiotherapy into clinical routine, allowing for direct visualisation of the tumour and healthy tissues before each session and live-tracking of the tumour during treatment, may foster better integration of stereotactic body radiotherapy into management of liver metastases [59].

Selective internal radiation therapy

Selective internal radiation therapy is an internal, localised radiotherapy using Yttrium-90 (90Y, β-particles), which has a short radiation range (1 cm) and a half-life of <3 days (see fig. 1 for illustration). The radioactive isotope is infused into either resin or glass particles. Using an angiography targeting the branch of the hepatic artery supplying the tumour, selective administration of the radioactive isotope is achieved by infusion of 90Y microspheres through the selectively placed catheter. Complete response after selective internal radiation therapy is rarely achieved for CRLM, but stable disease is seen in many patients [60, 61]. High pre-treatment tumour volume has been shown to be an independent predictor of inferior overall survival after selective internal radiation therapy. A recently published joint analysis [62] of three studies with 549 patients assigned to FOLFOX alone and 554 patients assigned FOLFOX plus selective internal radiation therapy [62] revealed that local selective internal radiation therapy significantly reduced the incidence of radiological progression within the liver, but that selective internal radiation therapy did not have an influence on progression-free survival or median overall survival (23 vs 23 months). Additionally, toxicity was significantly increased in the selective internal radiation therapy group. Therefore, routine integration of selective internal radiation therapy into FOLFOX-based first-line chemotherapy cannot be recommended for metastatic CRC at this time.

Liver transplantation for non-resectable colorectal liver metastases

  • For non-resectable CRLM, orthotopic liver transplantation provides better survival results compared to palliative chemotherapy.
  • Orthotopic liver transplantation for non-resectable CRLM is only for carefully selected patients, such as those with resection of the primary more than 18 m, total hepatic tumour diameter not more than 6 cm, carcinoembryonic antigen <80 μg/l, a BRAF wild type and stable disease under chemotherapy.

A possible therapy for end-stage liver diseases and selected primary or metastatic liver tumours is an orthotopic liver transplantation. However, strict criteria must be met to secure a reasonable outcome after orthotopic liver transplantation. Life-long immunosuppression may enhance the risk of tumour recurrence, with poorer outcomes [63]. The first seven human orthotopic liver transplants were performed for liver malignancies in the years 1963 and 1964. However, only two of these were for CRLM [64]. From 1985 to 1994, the overall survival after orthotopic liver transplantation reached 52–65%. Due to an increasing shortage of organs, indications for orthotopic liver transplantation because of liver malignancies had to be strongly justified, leading to more restrictive indications in many guidelines [63, 65, 66].

Orthotopic liver transplantation was abandoned for many types of tumours, including CRLM, in the 1990s due to a very poor 5-year survival rate of only 12–18% [6668]. Since then, the oncologic management of CRLM has evolved dramatically, with the availability of new immunosuppressive agents such as mTOR (mammalian target of rapamycin) inhibitors conferring antineoplastic effects [6769]. These advances encouraged a Norwegian group to re-introduce orthotopic liver transplantation indication in selected cases of CRLM. Such a study was possible in Norway because the average waiting time for a cadaveric graft is <1 month. The surfeit of donor livers has stimulated a study investigating the potential role of orthotopic liver transplantation in long-term survival for non-resectable CRLM [68]. The 5-year survival rate was surprisingly high, at 60% (21 patients). Nevertheless, recurrence was seen in 19 out of 21 patients after a median of 6 months. Recurrent tumours were treated with surgery or local ablation. After a median of 27 months, 33% of patients were tumour free. In this study, first-line chemotherapy for non-resectable CRLM demonstrated a 5-year survival rate of 9%, while patients undergoing orthotopic liver transplantation had a 5-year survival rate of 56%. Disease-free survival did not differ between these two groups. Despite these spectacular results in Norway, widespread use of orthotopic liver transplantation in other countries is currently compromised due to donor shortages. At the University Hospital Zurich, we do offer orthotopic liver transplantation for selected patients, mostly those with tumours that have been well-controlled by chemotherapy for at least 6 months. Due to the lack of available cadaveric grafts, we preferentially offer living donor liver transplantation.


In recent years, the management of CRLM has seen several advances, including novel imaging and molecular modalities which can be used to adjust treatment more precisely and in a more personalised manner, and which are routinely discussed at our weekly multidisciplinary team meetings. Different strategies for the resection of CRLM, like the classic, simultaneous and liver first approaches, are established for different, well-defined scenarios [10]. In particular cases, we have opted for aggressive approaches, sometimes combining two-stage procedures like ALPPS to enable curative resection in patients with very small, intra-arterial chemotherapy, and eventually orthotopic liver transplantation.

In a rapidly evolving field, different regimens of systemic and local chemotherapy, including different antibodies depending on the mutational status, are used to convert non-resectable hepatic metastatic disease into a resectable situation, providing a chance of cure. Additive tools such as thermal and non-thermal ablative procedures are essential for individually tailoring CRLM treatment options, especially when surgical interventions alone are limited due to proximity of tumours to central vascular or biliary structures. The combination of ablation and surgery is often chosen when aiming for a parenchyma-sparing procedure with respect to the disease course and liver tissue quality. Stereotactic radiation treatment of CRLM offers a non-invasive treatment in tumours greater than 3 cm in size, even in high-risk situations or sick patients, with acceptable results and limited impact on quality of life.

Because many modern, individually tailored multimodal concepts require a strong and demanding adherence of patients to long-term therapies, doctors must lead comprehensive, interdisciplinary conversations with patients and their families in order to make adequate decisions in the fight against CRLM.


The authors would like to thankCarol De Simio-Hilton for her wonderful illustrations.

Disclosure statement

No financial support and no other potential conflicts of interest relevant to this article was reported.


Pierre-Alain Clavien MD, PhD, Department of Surgery and Transplantation, Swiss Hepato-pancreato-biliary Centre,, University Hospital Zurich, Raemistrasse 100, CH-8091 Zurich, Clavien[at]


1 July, 20th, 2020.

2 Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin. 2015;65(2):87–108. Published online February 06, 2015. doi:. PubMed

3 Poston GJ, Adam R, Alberts S, Curley S, Figueras J, Haller D, et al.OncoSurge: a strategy for improving resectability with curative intent in metastatic colorectal cancer. J Clin Oncol. 2005;23(28):7125–34. Published online September 30, 2005. doi:. PubMed

4 Slesser AA, Simillis C, Goldin R, Brown G, Mudan S, Tekkis PP. A meta-analysis comparing simultaneous versus delayed resections in patients with synchronous colorectal liver metastases. Surg Oncol. 2013;22(1):36–47. Published online December 21, 2012. doi:. PubMed

5 Hackl C, Neumann P, Gerken M, Loss M, Klinkhammer-Schalke M, Schlitt HJ. Treatment of colorectal liver metastases in Germany: a ten-year population-based analysis of 5772 cases of primary colorectal adenocarcinoma. BMC Cancer. 2014;14(1):810. doi:. PubMed

6 Manfredi S, Lepage C, Hatem C, Coatmeur O, Faivre J, Bouvier AM. Epidemiology and management of liver metastases from colorectal cancer. Ann Surg. 2006;244(2):254–9. doi:. PubMed

7 Nordlinger B, Sorbye H, Glimelius B, Poston GJ, Schlag PM, Rougier P, et al.; EORTC Gastro-Intestinal Tract Cancer Group; Cancer Research UK; Arbeitsgruppe Lebermetastasen und-tumoren in der Chirurgischen Arbeitsgemeinschaft Onkologie (ALM-CAO); Australasian Gastro-Intestinal Trials Group (AGITG); Fédération Francophone de Cancérologie Digestive (FFCD). Perioperative chemotherapy with FOLFOX4 and surgery versus surgery alone for resectable liver metastases from colorectal cancer (EORTC Intergroup trial 40983): a randomised controlled trial. Lancet. 2008;371(9617):1007–16. doi:. PubMed

8 Wagner JS, Adson MA, Van Heerden JA, Adson MH, Ilstrup DM. The natural history of hepatic metastases from colorectal cancer. A comparison with resective treatment. Ann Surg. 1984;199(5):502–8. doi:. PubMed

9 Lehmann K, Rickenbacher A, Weber A, Pestalozzi BC, Clavien PA. Chemotherapy before liver resection of colorectal metastases: friend or foe?Ann Surg. 2012;255(2):237–47. Published online November 02, 2011. doi:. PubMed

10 Petrowsky H, Fritsch R, Guckenberger M, De Oliveira ML, Dutkowski P, Clavien PA. Modern therapeutic approaches for the treatment of malignant liver tumours. Nat Rev Gastroenterol Hepatol. 2020;17(12):755–72; Epub ahead of print. doi:. PubMed

11 Nordlinger B, Sorbye H, Glimelius B, Poston GJ, Schlag PM, Rougier P, et al.; EORTC Gastro-Intestinal Tract Cancer Group; Cancer Research UK; Arbeitsgruppe Lebermetastasen und–tumoren in der Chirurgischen Arbeitsgemeinschaft Onkologie (ALM-CAO); Australasian Gastro-Intestinal Trials Group (AGITG); Fédération Francophone de Cancérologie Digestive (FFCD). Perioperative FOLFOX4 chemotherapy and surgery versus surgery alone for resectable liver metastases from colorectal cancer (EORTC 40983): long-term results of a randomised, controlled, phase 3 trial. Lancet Oncol. 2013;14(12):1208–15. doi:. PubMed

12 Van Cutsem E, Cervantes A, Adam R, Sobrero A, Van Krieken JH, Aderka D, et al.ESMO consensus guidelines for the management of patients with metastatic colorectal cancer. Ann Oncol. 2016;27(8):1386–422. Published online July 07, 2016. doi:. PubMed

13 Niekel MC, Bipat S, Stoker J. Diagnostic imaging of colorectal liver metastases with CT, MR imaging, FDG PET, and/or FDG PET/CT: a meta-analysis of prospective studies including patients who have not previously undergone treatment. Radiology. 2010;257(3):674–84. Published online September 11, 2010. doi:. PubMed

14 Chu QD, Volmer CM, Zibari GB, Orloff SL, Williams M, Gimenez ME, eds. Hepato-Pancreato-Biliary and Transplant Surgery: Practical Management of Dilemmas. AHPBA: Beaux Books; 2018.

15 Moulton CA, Gu CS, Law CH, Tandan VR, Hart R, Quan D, et al.Effect of PET before liver resection on surgical management for colorectal adenocarcinoma metastases: a randomized clinical trial. JAMA. 2014;311(18):1863–9. Published online May 16, 2014. doi:. PubMed

16 Pugh RN, Murray-Lyon IM, Dawson JL, Pietroni MC, Williams R. Transection of the oesophagus for bleeding oesophageal varices. Br J Surg. 1973;60(8):646–9. Published online August 01, 1973. doi:. PubMed

17 Child CG (ed.) The Liver and Portal Hypertension. Philadelphia and London: W. B. Saunders Co. Ltd; 1964.

18 Zipprich A, Kuss O, Rogowski S, Kleber G, Lotterer E, Seufferlein T, et al.Incorporating indocyanin green clearance into the Model for End Stage Liver Disease (MELD-ICG) improves prognostic accuracy in intermediate to advanced cirrhosis. Gut. 2010;59(7):963–8. Published online June 29, 2010. doi:. PubMed

19 Stauber RE, Wagner D, Stadlbauer V, Palma S, Gurakuqi G, Kniepeiss D, et al.Evaluation of indocyanine green clearance and model for end-stage liver disease for estimation of short-term prognosis in decompensated cirrhosis. Liver Int. 2009;29(10):1516–20. doi:. PubMed

20 Lisotti A, Azzaroli F, Buonfiglioli F, Montagnani M, Cecinato P, Turco L, et al.Indocyanine green retention test as a noninvasive marker of portal hypertension and esophageal varices in compensated liver cirrhosis. Hepatology. 2014;59(2):643–50. Published online September 17, 2013. doi:. PubMed

21 de Liguori Carino N, O’Reilly DA, Dajani K, Ghaneh P, Poston GJ, Wu AV. Perioperative use of the LiMON method of indocyanine green elimination measurement for the prediction and early detection of post-hepatectomy liver failure. Eur J Surg Oncol. 2009;35(9):957–62. doi:. PubMed

22 Ray S, Mehta NN, Golhar A, Nundy S. Post hepatectomy liver failure - A comprehensive review of current concepts and controversies. Ann Med Surg (Lond). 2018;34(34):4–10. doi:. PubMed

23 Ge PL, Du SD, Mao YL. Advances in preoperative assessment of liver function. Hepatobiliary Pancreat Dis Int. 2014;13(4):361–70. Published online August 08, 2014. doi:. PubMed

24 Hoekstra LT, de Graaf W, Nibourg GA, Heger M, Bennink RJ, Stieger B, et al.Physiological and biochemical basis of clinical liver function tests: a review. Ann Surg. 2013;257(1):27–36. Published online July 28, 2012. doi:. PubMed

25 Mizuguchi T, Kawamoto M, Meguro M, Hui TT, Hirata K. Preoperative liver function assessments to estimate the prognosis and safety of liver resections. Surg Today. 2014;44(1):1–10. Published online March 12, 2013. doi:. PubMed

26 Du ZG, Li B, Wei YG, Yin J, Feng X, Chen X. A new scoring system for assessment of liver function after successful hepatectomy in patients with hepatocellular carcinoma. Hepatobiliary Pancreat Dis Int. 2011;10(3):265–9. Published online June 15, 2011. doi:. PubMed

27 Lock JF, Westphal T, Rubin T, Malinowski M, Schulz A, Jara M, et al.LiMAx Test Improves Diagnosis of Chemotherapy-Associated Liver Injury Before Resection of Colorectal Liver Metastases. Ann Surg Oncol. 2017;24(9):2447–55. Published online May 19, 2017. doi:. PubMed

28 Bennink RJ, Dinant S, Erdogan D, Heijnen BH, Straatsburg IH, van Vliet AK, et al.Preoperative assessment of postoperative remnant liver function using hepatobiliary scintigraphy. J Nucl Med. 2004;45(6):965–71. PubMed

29 Clavien PA, Petrowsky H, DeOliveira ML, Graf R. Strategies for safer liver surgery and partial liver transplantation. N Engl J Med. 2007;356(15):1545–59. Published online April 13, 2007. doi:. PubMed

30 Nordlinger B, Guiguet M, Vaillant JC, Balladur P, Boudjema K, Bachellier P, et al.; Association Française de Chirurgie. Surgical resection of colorectal carcinoma metastases to the liver. A prognostic scoring system to improve case selection, based on 1568 patients. Cancer. 1996;77(7):1254–62. Published online April 01, 1996. doi:.<1254::AID-CNCR5>3.0.CO;2-I PubMed

31 Mitry E, Fields AL, Bleiberg H, Labianca R, Portier G, Tu D, et al.Adjuvant chemotherapy after potentially curative resection of metastases from colorectal cancer: a pooled analysis of two randomized trials. J Clin Oncol. 2008;26(30):4906–11. Published online September 17, 2008. doi:. PubMed

32 Baltatzis M, Chan AK, Jegatheeswaran S, Mason JM, Siriwardena AK. Colorectal cancer with synchronous hepatic metastases: Systematic review of reports comparing synchronous surgery with sequential bowel-first or liver-first approaches. Eur J Surg Oncol. 2016;42(2):159–65. doi:. PubMed

33 de Haas RJ, Adam R, Wicherts DA, Azoulay D, Bismuth H, Vibert E, et al.Comparison of simultaneous or delayed liver surgery for limited synchronous colorectal metastases. Br J Surg. 2010;97(8):1279–89. Published online June 26, 2010. doi:. PubMed

34 Mentha G, Majno PE, Andres A, Rubbia-Brandt L, Morel P, Roth AD. Neoadjuvant chemotherapy and resection of advanced synchronous liver metastases before treatment of the colorectal primary. Br J Surg. 2006;93(7):872–8. Published online May 04, 2006. doi:. PubMed

35 Zorzi D, Mullen JT, Abdalla EK, Pawlik TM, Andres A, Muratore A, et al.Comparison between hepatic wedge resection and anatomic resection for colorectal liver metastases. J Gastrointest Surg. 2006;10(1):86–94. Published online December 22, 2005. doi:. PubMed

36 Hamady ZZ, Lodge JP, Welsh FK, Toogood GJ, White A, John T, et al.One-millimeter cancer-free margin is curative for colorectal liver metastases: a propensity score case-match approach. Ann Surg. 2014;259(3):543–8. Published online June 05, 2013. doi:. PubMed

37 Hammond JS, Muirhead W, Zaitoun AM, Cameron IC, Lobo DN. Comparison of liver parenchymal ablation and tissue necrosis in a cadaveric bovine model using the Harmonic Scalpel, the LigaSure, the Cavitron Ultrasonic Surgical Aspirator and the Aquamantys devices. HPB (Oxford). 2012;14(12):828–32. doi:. PubMed

38 Eshmuminov D, Raptis DA, Linecker M, Wirsching A, Lesurtel M, Clavien PA. Meta-analysis of associating liver partition with portal vein ligation and portal vein occlusion for two-stage hepatectomy. Br J Surg. 2016;103(13):1768–82. Published online September 17, 2016. doi:. PubMed

39 de Santibañes E, Clavien PA. Playing Play-Doh to prevent postoperative liver failure: the “ALPPS” approach. Ann Surg. 2012;255(3):415–7. Published online February 15, 2012. doi:. PubMed

40 Langiewicz M, Schlegel A, Saponara E, Linecker M, Borger P, Graf R, et al.Hedgehog pathway mediates early acceleration of liver regeneration induced by a novel two-staged hepatectomy in mice. J Hepatol. 2017;66(3):560–70. Published online October 25, 2016. doi:. PubMed

41 Petrowsky H, Györi G, de Oliveira M, Lesurtel M, Clavien PA. Is partial-ALPPS safer than ALPPS? A single-center experience. Ann Surg. 2015;261(4):e90–2. Published online February 24, 2015. doi:. PubMed

42 Moris D, Ronnekleiv-Kelly S, Kostakis ID, Tsilimigras DI, Beal EW, Papalampros A, et al.Operative Results and Oncologic Outcomes of Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy (ALPPS) Versus Two-Stage Hepatectomy (TSH) in Patients with Unresectable Colorectal Liver Metastases: A Systematic Review and Meta-Analysis. World J Surg. 2018;42(3):806–15. Published online August 12, 2017. doi:. PubMed

43 Lau WY, Lai EC. Modifications of ALPPS - from complex to more complex or from complex to less complex operations. Hepatobiliary Pancreat Dis Int. 2017;16(4):346–52. Published online August 22, 2017. doi:. PubMed

44 Linecker M, Stavrou GA, Oldhafer KJ, Jenner RM, Seifert B, Lurje G, et al.The ALPPS Risk Score: Avoiding Futile Use of ALPPS. Ann Surg. 2016;264(5):763–71. Published online October 18, 2016. doi:. PubMed

45 Eshmuminov D, Tschuor C, Raptis DA, Boss A, Wurnig MC, Sergeant G, et al.Rapid liver volume increase induced by associating liver partition with portal vein ligation for staged hepatectomy (ALPPS): Is it edema, steatosis, or true proliferation?Surgery. 2017;161(6):1549–52. Published online April 16, 2017. doi:. PubMed

46 Wakabayashi G, Cherqui D, Geller DA, Buell JF, Kaneko H, Han HS, et al.Recommendations for laparoscopic liver resection: a report from the second international consensus conference held in Morioka. Ann Surg. 2015;261(4):619–29. Published online March 06, 2015. doi:. PubMed

47 Fretland AA, Dagenborg VJ, Bjørnelv GMW, Kazaryan AM, Kristiansen R, Fagerland MW, et al.Laparoscopic Versus Open Resection for Colorectal Liver Metastases: The OSLO-COMET Randomized Controlled Trial. Ann Surg. 2018;267(2):199–207. Published online June 29, 2017. doi:. PubMed

48 Aghayan DL, Fretland AA, Kazaryan AM, Sahakyan MA, Dagenborg VJ, Bjørnbeth BA, et al.Laparoscopic versus open liver resection in the posterosuperior segments: a sub-group analysis from the OSLO-COMET randomized controlled trial. HPB (Oxford). 2019;21(11):1485–90. Published online April 10, 2019. doi:. PubMed

49 Clavien PA, Barkun J. Consensus conference on laparoscopic liver resection: a jury-based evaluation. Ann Surg. 2015;261(4):630–1. Published online March 06, 2015. doi:. PubMed

50 Abu Hilal M, Aldrighetti L, Dagher I, Edwin B, Troisi RI, Alikhanov R, et al.The Southampton Consensus Guidelines for Laparoscopic Liver Surgery: From Indication to Implementation. Ann Surg. 2018;268(1):11–8. Published online October 25, 2017. doi:. PubMed

51 Fruscione M, Pickens R, Baker EH, Cochran A, Khan A, Ocuin L, et al.Robotic-assisted versus laparoscopic major liver resection: analysis of outcomes from a single center. HPB (Oxford). 2019;21(7):906–11. Published online January 09, 2019. doi:. PubMed

52 Seror O. Ablative therapies: Advantages and disadvantages of radiofrequency, cryotherapy, microwave and electroporation methods, or how to choose the right method for an individual patient?Diagn Interv Imaging. 2015;96(6):617–24. Published online May 20, 2015. doi:. PubMed

53 Loveman E, Jones J, Clegg AJ, Picot J, Colquitt JL, Mendes D, et al.The clinical effectiveness and cost-effectiveness of ablative therapies in the management of liver metastases: systematic review and economic evaluation. Health Technol Assess. 2014;18(7):vii–viii, 1–283. doi:. PubMed

54 Coletti L, Battaglia V, De Simone P, Turturici L, Bartolozzi C, Filipponi F. Safety and feasibility of electrochemotherapy in patients with unresectable colorectal liver metastases: A pilot study. Int J Surg. 2017;44:26–32. doi:. PubMed

55 Dawson LA, Normolle D, Balter JM, McGinn CJ, Lawrence TS, Ten Haken RK. Analysis of radiation-induced liver disease using the Lyman NTCP model. Int J Radiat Oncol Biol Phys. 2002;53(4):810–21. Published online July 04, 2002. doi:. PubMed

56 Petrelli F, Comito T, Barni S, Pancera G, Scorsetti M, Ghidini A; SBRT for CRC liver metastases. Stereotactic body radiotherapy for colorectal cancer liver metastases: A systematic review. Radiother Oncol. 2018;129(3):427–34. Published online July 13, 2018. doi:. PubMed

57 Lee J, Shin IS, Yoon WS, Koom WS, Rim CH. Comparisons between radiofrequency ablation and stereotactic body radiotherapy for liver malignancies: Meta-analyses and a systematic review. Radiother Oncol. 2020;145:63–70. Published online January 11, 2020. doi:. PubMed

58 Jackson WC, Tao Y, Mendiratta-Lala M, Bazzi L, Wahl DR, Schipper MJ, et al.Comparison of Stereotactic Body Radiation Therapy and Radiofrequency Ablation in the Treatment of Intrahepatic Metastases. Int J Radiat Oncol Biol Phys. 2018;100(4):950–8. doi:. PubMed

59 Witt JS, Rosenberg SA, Bassetti MF. MRI-guided adaptive radiotherapy for liver tumours: visualising the future. Lancet Oncol. 2020;21(2):e74–82. Published online February 03, 2020. doi:. PubMed

60 Vilgrain V, Pereira H, Assenat E, Guiu B, Ilonca AD, Pageaux GP, et al.; SARAH Trial Group. Efficacy and safety of selective internal radiotherapy with yttrium-90 resin microspheres compared with sorafenib in locally advanced and inoperable hepatocellular carcinoma (SARAH): an open-label randomised controlled phase 3 trial. Lancet Oncol. 2017;18(12):1624–36. Published online November 07, 2017. doi:. PubMed

61 Morse MA, Hanks BA, Suhocki P, Doan PL, Liu EA, Frost P, et al.Improved time to progression for transarterial chemoembolization compared with transarterial embolization for patients with unresectable hepatocellular carcinoma. Clin Colorectal Cancer. 2012;11(3):185–90. Published online January 28, 2012. doi:. PubMed

62 Wasan HS, Gibbs P, Sharma NK, Taieb J, Heinemann V, Ricke J, et al.; FOXFIRE trial investigators; SIRFLOX trial investigators; FOXFIRE-Global trial investigators. First-line selective internal radiotherapy plus chemotherapy versus chemotherapy alone in patients with liver metastases from colorectal cancer (FOXFIRE, SIRFLOX, and FOXFIRE-Global): a combined analysis of three multicentre, randomised, phase 3 trials. Lancet Oncol. 2017;18(9):1159–71. doi:. PubMed

63 Dutkowski P, De Rougemont O, Müllhaupt B, Clavien PA. Current and future trends in liver transplantation in Europe. Gastroenterology. 2010;138(3):802–9.e4. doi:. PubMed

64 Starzl TE. The saga of liver replacement, with particular reference to the reciprocal influence of liver and kidney transplantation (1955-1967). J Am Coll Surg. 2002;195(5):587–610. doi:. PubMed

65 Gores GJ. Liver transplantation for malignant disease. Gastroenterol Clin North Am. 1993;22(2):285–99. Published online June 01, 1993. PubMed

66 Penn I. Hepatic transplantation for primary and metastatic cancers of the liver. Surgery. 1991;110(4):726–34, discussion 734–5. Published online October 01, 1991. PubMed

67 Moris D, Tsilimigras DI, Chakedis J, Beal EW, Felekouras E, Vernadakis S, et al.Liver transplantation for unresectable colorectal liver metastases: A systematic review. J Surg Oncol. 2017;116(3):288–97. doi:. PubMed

68 Hagness M, Foss A, Line PD, Scholz T, Jørgensen PF, Fosby B, et al.Liver transplantation for nonresectable liver metastases from colorectal cancer. Ann Surg. 2013;257(5):800–6. Published online January 31, 2013. doi:. PubMed

69 Toso C, Pinto Marques H, Andres A, Castro Sousa F, Adam R, Kalil A, et al.; Compagnons Hépato-Biliaires Group. Liver transplantation for colorectal liver metastasis: Survival without recurrence can be achieved. Liver Transpl. 2017;23(8):1073–6. doi:. PubMed

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