Colorectal Liver Metastases
DEFINITION
Colorectal mets to the liver.  Main focus here is on management
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EPIDEMIOLOGY

See colorectal cancer notes.
Most common liver malignancies
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AETIOLOGY

Colorectal AdenoCa

BIOLOGICAL BEHAVIOUR

Natural history
Negative prognostic factors:
- 4+ mets
- large mets
- poorly differentiated primary tumours or lymph node invasion.
- extra-hepatic disease
- high CEA
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MANIFESTATIONS

Appear hard, rubbery, 'umbilicated', may pucker the capsule, can make it convex.
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INVESTIGATIONS
Biochemistry

Haematology

Microbiology

Imaging
Contrast CT of chest, abdo and pelvis followed b contrast MRI for those who appear resectability
- MRI most sensitive for small mets and essential to be adequately worked up
Various tools are available to asses FLRs.
Essential that relationships of metastatic disease to crucial structures is appreciated.
PET is commonly used; role is to detect extra-hepatic disease.
- RCT shows decreased incidence of futile laparotomy from 45 to 28% without adversely affecting disease free survival.

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MANAGEMENT

Prognosis
Systematic review shows:
- 30% patients receive 5-yr survival.
- 20% receive 10-yr survival
- further relapse beyond 10yr uncommon.
Hence, cure seems possible
But no RCTs

Ablation
Among options (RFA, Perc ethanol and Microwave ablation), RFA has become ?most promising and most commonly used
RFA uses AC current to achieve thermal destruction.
- can be of curative intent
Needle electrode and dispersive grounding electrodes
--> destroys tumour and surrounding liver tissues
RFA can be used intraoperatively under US guidance or under MRI / CT in radiology
-if no previous biopsy, might pay to do a core biopsy under US.
Careful planning needed to achieve appropriate necrosis
- can ablate up to 7cm diameter
Location of tumor is important
- near portal pedicles, near porta = relative contraindications
- tumours >4-5cm show high rates of local recurrence.
Identify target (in two planes if with US) monitor tissue impedance and current / temperature
Determining success is done with contrast enhanced CT or MRI within 30d
- then serial follow up imaging.
Outcomes
Evidence is quite limited; no RCTs comparing its use to surgery
Local recurrence varies widely in reports
5-yr survival probably inferior to surgery.
- difficult as confounding factors in comparisons; adequacy of RFA variable and unclear R status.
Surgery remains the treatment of choice, but these are important for localised unresectable disease, distribution, recurrence

Role of Cytotoxic Chemotherapy
Downstaging can allow resectability; shown for oxaliplatin and fluoropyrimidine.
- outcome same as up-front resectable tumors.
Conversion to resectability is very significant prognostically; responsive tumor; better 5 yr survival
Also use in all patients regardless of resectability
- 8% increase in progression free survival at 3 yrs.

Surgery: Indications and resectability
These issues are intrinsically linked
Standard answer is:
- if resectable, do it
- need inflow (portal v. and hepatic a.), outflow (hepatic v.), biliary drainage and adequate functional remnant.
- need at least 2 segments remaining and in continuity
- and remnant should be >25% of remaining total functional liver volume else mortality and complications are high (based on imaging)
= "future liver remnant"
--> survival with 25% remnant clearly requires healthy liver; absence of cirrhosis or chemotherapy-associated steatohepatosis (CASH).
- clearly v. important as most pts have chemo
Even repeat hepatectomies can be undertaken in view of regenerative liver capacity.
Techniques are available to "grow" liver to facilitate resection; discussed below.
Laparoscopy
10-20% will be found to have unresectable disease
In addition, intra-operative US will frequently detect lesions undetected by external modalities; well worthwhile before resection.

Techniques to Increase FLR
Two options: staged resections and portal vein embolization.
- in staged resection, one lobe is cleared or resected initially, then other side after 4w+
- in pve, the good side is preserved, other knocked off, causing hypertrophy and atrophy respectively.
--> almost no symptoms and performed as a day case; FLR can be improved 30%+ by this technique

Operative
Principles
Margin of 10mm is preferred, but in practice most CR mets are "pushing" rather than infiltrative such that any slim margin is evidence-based
Modern liver surgery is safe, with mortality approaching 1%
- reduced blood loss is a primary factor.
- most patients will not require a transfusion and cross-matching is no longer routine...
Surgery is a team enterprise and close involvement of the anesthetist is essential
- with Pringle on, the only bleeding can arise from the hepatic veins
- CVP needs to be kept low.
--> then, if the vein is opened, often it won't bleed much due to zero-pressure difference.
Often complete inflow occlusion is unnecessary.
- often, in a partial hepatectomy, inflow is dealt with early, and there is little crossover within the liver; then hepatic vein taken.
Laparoscopic approaches are possible.
- difficult though. Require substantial experience. Hepatic veins dealt to last, otherwise quite similar.

Dealing with the parenchyma
Solid organ division is technically challenging and is specialist territory.
Previous finger-fracture technique was rough and imprecise, leading to bleeding from small vessels and fragile hepatic veins.
Modern instrumentation is used to identify blood vessels and bile ducts that must be closed to prevent complications.
- ultrasound aspirator (CUSA) uses ultrasound to destroy parenchymal content without damaging fibrous vascular structures.
- with experience, possible to avoid even small structures; with inexperience even large structures will be damaged.
Note the instrument produces a margin beyond what is apparent on histology.
At the end of the day, the surgeon's technique and skill are paramount over choice of instrumentation.

Argon
Can be used to seal blood vessels.
An inert gas, and enables high temps to be delivered to tissues, sealing vessels without charring.

What about the "disappearing met"?
Some patients get complete response and the tumor disappears on imaging.
- evidence suggests that they are not sterilized and will grow again if untreated.
--> remove; if unremovable, ablation if reappear on repeat imaging.
Clear margins are a reliable sign of an adequate resection here.

Adjuvant Surgery?
Debulking rather than curative
- probably has a survival benefit, currently unproven.
Survival benefit has been shown in ablation.
Way forward would seem to favor a radical surgical approach in pts responding to chemo.

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REFERENCES
British Journal of Cancer 102, 1313 (2010). doi:10.1038/sj.bjc.6605659
Cameron 10th