Editing 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'''
{| class="wikitable"
|'''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

[[Category:Liver]]