Liver metastases

The most common malignant tumours of the liver

• The large majority will have unresectable liver or extra-hepatic malignancy
• Surgeons will be involved with select cases only
• Describe as synchronous or metachronous (>1 year after primary disease was diagnosed)
  • Synchronous has a worse prognosis

Potential sources:

• GIT
  • Colon/rectum
  • Stomach
  • Pancreas
  • Biliary
• Genitourinary
  • Renal
  • Prostate
• Neuroendocrine
• Breast
• Eye (melanoma)
• Skin (melanoma)
• Soft tissue (retroperitoneal sarcoma)
• Gynaecologic
  • Ovarian
  • Endometrial
  • Cervical
• Remember - metastatic adenocarcinoma to the liver of unknown primary is often intra-hepatic cholangiocarcinoma

Imaging:

• Hypodense, hypovascular
• See 'Radiology' section for more

CRC liver mets

• Epidemiology
  • Far more common than primary liver tumours
  • 1/3 of patients with new diagnosis of CRC have liver mets
  • 5-10% of patients with hepatic CRC mets are candidates for resection
• Presentation
  • Patients presenting with symptomatic disease (pain, ascites, jaundice, weight loss, palpable mass) have poor prognosis
  • Patients that may benefit from resection (isolated met) are more likely to be found on surveillance
  • In particular, this is the main reason to do CT surveillance post-op in CRC resection patients
  • Mild elevations in LFTs (ALP, GGT, LDH) are common but not as effective as CEA in surveillance
• Workup
  • Consider biopsy - although probably not necessary in patients with history of CRC, characteristic cross-sectional imaging, and elevated CEA.
  • Colonoscopy if it has been >1 year since the last scope
  • Chest CT often performed but is of low yield
  • PET does not significantly effect outcomes in this setting
  • Staging laparoscopy spares 10% of patients a non-therapeutic laparotomy - especially useful in those with poor prognostic indicators
• Treatment
  • No RCT has ever been performed comparing surgery with no treatment or chemotherapy
  • Surgical resection is preferred, although other options such as stereotactic RT and ablation can be considered. Goal is to remove all mets with R0.
    • Contraindications: comorbidities, insufficient liver reserve, metastatic disease.
  • Situations:
    • Bilateral mets - major resection can be combined with wedge resection or ablation of the lesions on the contralateral side
    • Synchronous mets:
      • Simultaneous liver and colonic resection can be considered as long as one of the operations is minor - don't do two major procedures together. Generally try to do liver resection first.
      • Most often, patients will have a few months of neoadjuvant chemo, then liver resection, then bowel resection. Need to time carefully - many CTX regimes are hepatotoxic.
    • Unresectable liver-only metastatic disease: pre-operative systemic and HAI CTX will convert some into resection candidates, with comparable outcomes to those who were up-front resectable.
  • Neoadjuvant chemotherapy
    • Common strategy to treat occult systemic disease
    • Allows detection of patients who will have progression while on chemotherapy, a poor prognostic indicator
  • Indications for liver resection:

Conventional indications versus modern approach to treatment of hepatic colorectal metastases

Conventional indications	Modern aggressive approach
<4 metastases, unilobar disease	No limits. Multiple/bilobar metastases acceptable, using neoadjuvant chemotherapy, staged resection, and resection/local ablative therapy.
Size <5 cm	No limits
No extrahepatic disease	Pulmonary metastases can be resected
Resection margin >1 cm	Resection margin <1 cm managed with ablative treatment of narrow margin (cryosurgery or radiofrequency ablation)
Adequate remnant liver parenchyma	Preoperative portal vein embolization to increase liver remnant volume
Resection of all macroscopic disease	NED can be achieved with combination of resection and local ablative therapy
No metachronous liver metastases	Synchronous and metachronous metastases acceptable
Absence of vena cava and hepatic vein confluence invasion	No limits. Caval/hepatic vein resection with reconstruction can be performed
Absence of hepatic pedicle lymph node metastases	In absence of celiac axis metastases, hepatic pedicle lymph node metastases may be resected for improved 3-year survival

NED: No evidence of disease.

• Ablation
  • Mechanism
    • Cause cell death by creating a zone of coagulative necrosis
  • Indications
    • Solitary tumours 0-5cm
    • Can be used in combination with resection to deal with multifocal mets
  • Techniques
    • Cryoablation
      • Uses the Joule-Thomson effect with argon gas to create repeated freeze-thaw cycles via insulated probes
      • Cumbersome, expensive
      • Mostly replaced by RFA
    • RFA
      • Most widely-used
      • Metal electrodes placed into tumour, dispersive grounding pads placed onto patient. High-frequency AC between 350-500kHz are passed through, generating extreme heat.
      • Efficacy decreases as tumour size increases - works well up to 3cm
      • Efficacy decreases when tumour is close to large blood vessel - continuous flow cools - 'heat-sink effect'
      • General indications are solitary lesions up to 3cm
    • Microwave ablation
      • High-frequency microwaves cause coagulative necrosis
      • More rapid rise in temperature and larger ablation zone than RFA
      • Less susceptible to heat-sink effect
      • Consider this instead of RFA for lesions 3-5cm or is in contact with a large vessel
    • Irreversible electroporation
      • Repeated electrical pulses irreversibly increases permeability of cell lipid layers
      • Needs muscle relaxant
  • Approaches
    • Percutaneous vs operative
    • Operative allows for diagnostic lap, exclusion of peritoneal mets
    • Can do pringle maneuvre, minimising heat sink effect
    • Can do ablation and resection simultaneously
  • Post-op
    • Imaging to evaluate efficacy of ablation
    • Compare pre and post-procedural images - size, shape and location of necrosis zone - look for 5-10mm margin
    • CT 1-4 weeks post-ablation, then every 3-4 months
    • PET can be used >3/12 down the track, once inflammation has subsided
• Chemoembolisation
  • Indications
    • Palliative treatment
    • Adjunct before tumour resection
    • Bridge to orthotopic liver transplant
  • Technique
    • Oil emulsion is used
    • Most commonly cisplatin, adriamycin/doxorubicin, and mitomycin
    • Access hepatic artery
  • Post-procedure
    • Monitor for AKI/ALI
    • Pain/nausea
    • Puncture site

• Adjuvant chemotherapy
  • Slightly improved survival for 6 months CTX post-resection (62 months vs 47 months)
  • Can be given as hepatic arterial infusion
• Prognosis
  • Without resection
    • Median survival 20 months or longer with modern CTX
    • However 5-year survival is rare
  • With resection
    • Fong criteria predicts survival after hepatic resection - one for each, predicts one-year survival
      • Node-positive primary
      • Disease-free interval <12 months
      • >1 tumour
      • Pre-op CEA > 200
      • Size of largest tumour >5cm
    • Resection of isolated colorectal cancer liver mets carries good overall survival, particularly in younger patients
    • Five-year survival rates 24-58%
    • Peri-operative mortality is low (2-5%), but morbidity is common
    • Important prognostic factors: size of largest met, presence of extrahepatic disease, nodal status of primary tumour

Neuroendocrine metastases

• Pathophysiology
  • Commonly gastrinomas, glucagonomas, somatostatinomas, and non-functional NETs
  • Insulinomas and carcinoid tumours don't commonly metastasise to liver
  • Typically slow-growing, indolent tumours
• Treatment is often aimed at relieving symptoms rather than cure
• Minimal good data due to rarity of condition
• In general, Sabiston's suggests surgical cytoreduction if >90% of tumour can likely be removed without prohibitive operative risk
• Formal R0 resection is not necessary - enucleation or wedge resection are options
• Ablative approaches can be used
• See main NET topic under 'small bowel' section

Other types of metastases

• General principles are similar as for colorectal mets
• Prognosis tends to be dismal with extra-hepatic disease, multiple tumours, large tumours, or a short disease-free interval
• Generally give neoadjuvant chemotherapy prior to any planned liver resection
• In most series, resection for genitourinary mets has the best prognosis
• In general, only offer surgery in the most favourable situations