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Liver metastases

Nature Reviews Disease Primers volume 7, Article number: 27 (2021) Cite this article

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Abstract

Liver metastases are commonly detected in a range of malignancies including colorectal cancer (CRC), pancreatic cancer, melanoma, lung cancer and breast cancer, although CRC is the most common primary cancer that metastasizes to the liver. Interactions between tumour cells and the tumour microenvironment play an important part in the engraftment, survival and progression of the metastases. Various cells including liver sinusoidal endothelial cells, Kupffer cells, hepatic stellate cells, parenchymal hepatocytes, dendritic cells, resident natural killer cells as well as other immune cells such as monocytes, macrophages and neutrophils are implicated in promoting and sustaining metastases in the liver. Four key phases (microvascular, pre-angiogenic, angiogenic and growth phases) have been identified in the process of liver metastasis. Imaging modalities such as ultrasonography, CT, MRI and PET scans are typically used for the diagnosis of liver metastases. Surgical resection remains the main potentially curative treatment among patients with resectable liver metastases. The role of liver transplantation in the management of liver metastasis remains controversial. Systemic therapies, newer biologic agents (for example, bevacizumab and cetuximab) and immunotherapeutic agents have revolutionized the treatment options for liver metastases. Moving forward, incorporation of genetic tests can provide more accurate information to guide clinical decision-making and predict prognosis among patients with liver metastases.

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Fig. 1: Metastatic invasion of tumour cells into the liver.
Fig. 2: Common primary cancers metastasizing to the liver.
Fig. 3: The phases of liver colonization by disseminated cancer cells.
Fig. 4: Reciprocal interactions between cancer cells and the various liver and immune cell types.
Fig. 5: Identification of colorectal liver metastasis with evidence of biliary dilatation on imaging studies.
Fig. 6: Imaging techniques to detect colorectal liver metastasis.

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Authors and Affiliations

  1. Department of Surgery, The Ohio State University, Wexner Medical Center, Columbus, OH, USA

    Diamantis I. Tsilimigras & Timothy M. Pawlik

  2. Departments of Surgery, Medicine and Oncology, McGill University, and the Research Institute of the McGill University Health Center, Montreal, QC, Canada

    Pnina Brodt

  3. Department of Surgery and Transplantation, University Hospital Zurich, Zurich, Switzerland

    Pierre-Alain Clavien

  4. Oxford Institute for Radiation Oncology, Department of Oncology, University of Oxford, Oxford, UK

    Ruth J. Muschel

  5. Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA

    Michael I. D’Angelica

  6. Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Japan

    Itaru Endo

  7. Department of Clinical Surgery, University of Edinburgh, Edinburgh, UK

    Rowan W. Parks

  8. Department of Surgery, Division of Abdominal Organ Transplantation, Washington University in St. Louis School of Medicine, Saint Louis, MO, USA

    Majella Doyle

  9. Department of Surgery, Division of HPB Surgery, Liver Transplant Unit, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina

    Eduardo de Santibañes

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  1. Diamantis I. Tsilimigras
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  2. Pnina Brodt
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  4. Ruth J. Muschel
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  5. Michael I. D’Angelica
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Contributions

Introduction (T.M.P. and D.I.T.); Epidemiology (D.I.T and P.-A.C.); Mechanisms/pathophysiology (P.B. and R.J.M.); Diagnosis, screening and prevention (I.E., E.d.S. and D.I.T.); Management (R.W.P., T.M.P. and D.I.T.); Quality of life (M.I.D.); Outlook (R.J.M. and M.D.); Overview of Primer (T.M.P.).

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Correspondence to Timothy M. Pawlik.

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Nature Reviews Disease Primers thanks H. Baba, M. Ducreux, P. Galle, G. Poston, M. Schmid and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Glossary

Left-sided tumours

Tumours that originate from the left descending colon.

Right-sided tumours

Tumours that originate from the first part of the colon corresponding to the ascending colon.

Conversion treatment

The use of cytotoxic drugs and/or chemotherapy that shrink the tumour to a level considered amenable to resection.

Stage M1c melanoma

The cancer has spread to any other location that does not involve the central nervous system.

Monosomy

The state of having a single copy of a chromosome pair in contrast to the usual two copies found in diploid cells.

Intravasation

Invasion of cancer cells through the basement membrane into a blood or lymphatic vessel.

Kupffer cells

Macrophages that are phagocytic and reside in sinusoids of the liver in proximity to the endothelial cells.

Sinusoidal vessels

Low-pressure vascular channels that receive blood from terminal branches of the hepatic artery and portal vein at the periphery of lobules and deliver it into central veins.

Space of Disse

The perisinusoidal space in the liver between a hepatocyte and a sinusoid.

Myelopoiesis

Process in which innate immune cells, such as neutrophils, dendritic cells and monocytes, develop from a myeloid progenitor cell.

Desmosomes

Specialized adhesive protein complexes that localize to intercellular junctions and are responsible for maintaining the mechanical integrity of tissues.

Ring enhancement

Characteristic feature in CT, which represents a zonal area of viable tumour cells.

Cytoreduction

Approach to cancer treatment that aims to reduce the number of cancer cells via resection of the primary tumour or metastatic deposits.

Future liver remnant

Volume of functional liver after resection

Cytokeratin

Type of structural protein that is expressed by the epithelial cells.

Microsatellite instability

The condition of genetic hypermutability (predisposition to mutation) that results from impaired DNA mismatch repair.

Hilar lymphadenopathy

Enlargement of lymph nodes at the hepatic hilum.

Disease-free interval

Interval from the treatment of the primary tumour to the detection of metastases.

Metachronous metastasis

Metastasis developed after a period of time from diagnosis of the primary tumour.

Hepatic hilum

Anatomical region where bile ducts, hepatic arterial branches, portal vein branches, lymphatics and nerves enter or leave the liver.

Heat-sink phenomenon

Phenomenon that limits ablation effectiveness when the target lesion is close (<1 cm) to a large blood vessel (≥3 mm diameter); the flowing blood causes a cooling effect, thereby reducing the ablation volume.

Local control rate

Rate of controlling cancer growth at the local site of origin.

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Tsilimigras, D.I., Brodt, P., Clavien, PA. et al. Liver metastases. Nat Rev Dis Primers 7, 27 (2021). https://doi.org/10.1038/s41572-021-00261-6

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