Liver Metastases
Jean-Bernard Poulard MD, MBA, FACS
Mount Sinai School of Medicine
Queens Hospital Center
Jamaica, NY
Liver Metastases
Liver Metastases
• 30 Years Ago, Considered Incurable
Liver Metastasis
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Extent of the problem
Primary Cancers and Mets
Liver structure and function considerations
Excision and its evolution
Chemo as an adjunct
Ablative Approaches
Current Recommendations
The Future
Liver Metastases- Biology
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Fertile Circulation. Systemic and Portal
Biliary Component
Primary Drainage for GI Tract /Pancreas
Functional Importance
Regenerative Capacity
Abused and Insult (alcohol and Viruses)
Liver Mets- Extant of Problem
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Demographics of Colorectal Cancer
Other Gastro-Intestinal Cancers
Other Sites
Sites Where Treatment Benefits
Sites with No Benefit
Liver Metastases
Practical Considerations
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Function
Accessability
Resectability
Technical Considerations (Support)
Equipment and Machinery
Surgical and Interventional Expertise
Critical Care
Liver Mets -Metastasectomy
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Indications
Tissue Diagnosis
Size and Number and Lobes
Timing
Chemo Pre-Resection?
Risks
Morbidity and Mortality
Outcome
Liver Mets - Metastasectomy
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Extra-Hepatic Disease: Containdication?
Used to Be
But if Extra-hepatic and Mets Resectable
If R0 Possible – 5 yr 29-38% (Elias et al,
BJS 2003; 90: 567-74)
Liver Metastases-HAI
• Rationale for Hepatic Artery Infusion
– Not Amenable to Excision
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Technical Considerations
Risks and Pitfalls (misperfusion, Art Injury)
Evolution and Current Practice
Chemo Agents: 5-FUDR (+ leucovorin and
Dexamethasone),
– Results: RR 78%, Median Survival 25 mos
Kemeny N. J Clin. Onc. 1994; 23:2288
Liver Metastases HAI 2
• Oxaliplatin and Irinotecan
– Scant Data but Safe via HA
– 28 Pts with Isolated Liver Mets
– Oxaliplatin Followed by IV 5-FU and
Leucovorin
– Objective RR 64% Median Survival 28 Mos
J. Clin. Onc. 2005; 23:275s
Liver Metastases-Ablation 1
• Indications
• Modalities
– Intratumoral, Cryo, Radiation, Thermal
• Common Attributes
• Degree of Invasiveness
Liver Metastases- Intratumoral
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Percutaneous Ethanol and Acetic Acid
Used in small HCC (Japan)
Difficult Access for Some Lesions
Etoh not Effective in Other Histologies
Consensus: Etoh not Appropriate
Acetic Acid
Liver Metastasis - Cryoablation
• Techniques
• Failure Rate: 10-44% (Most in Non-Frozen
sites)
• Sometimes after Incomplete Excision
• Survival 24-38% 5 year
• Drawback: Requires Laparotomy
• Obsolescent?
Liver Metastases- Radiation
• External Beam Therapy Limited
– Tolerance 35 Gy vs 70 Gy to Destroy CA
• Stereotactic for Small Tumors
• Brachytherapy : I-125 Seeds Rarely used after
Incomplete Excision
– Complex Logistics, Cryo Preferred
• Radioembolization
• Y-90 tagged Resin or Glass microspheres
• Used with HAI of FUDR (RR 44 vs 18)
• Similar Toxicity, No Signicant Survival Benefit (Xcpt>15)
Ann. Onc. 2001; 12: 1711
Liver Metastases
Thermal Ablation 1
• Modalities
– Radiofrequency Ablation
– Laser and Microwaves (Europe)
• Limitations
– Control of Margin
– Specificity of Tissue Damage
• Advantage
– Percutaneous Approach
Liver Metastases
• Radiofrequency Generator
Liver Metastases -RFA
• Used in HCC and Liver Mets
• Open, Laparoscopic or Percutaneous
– Relation to Recurrences
– Experience, Type of Equipment
• Pitfalls: Intestinal and Diaphragm Injuries
Portal Vein Thrombosis
• Mortality 0-2% Major Complications 6-9%
• Outcome: Median Survival 24 Months
Liver MetastasesRecommendations
• Resection for Cure is First Option
• Potentially Resectable if Lesions Smaller
– Systemic Chemo and Reevaluation
• Limited Number of Mets but Not Surgical
Candidate:
– Ablation (RFA Preferred)
– HAI
Liver Metastases- The Future
CRC
• The M.D. Anderson’s Approach
• Up to 1992, 35% Survival for Stage 4 CRC
• Post 1992, Up to 58%
– Anesthesia, Surgery, Hemostatics, Imaging,
Intesive Care
• Surgical Excision as Primary Tx –Better
• Chemo Alone or RFA <20%
• Solitary Met Excision 71% Survival 5 Yrs
Liver Metastasis- The Future 2
CRC
• Majority are Unresectable at Presentation
• Make Them Resectable?
• Prospective Trial
– Combination Chemotherapy
– Staged Hepatectomy
– Portal Vein Embolization
• Determine Remnant of Viable Liver
• Size and Number of Mets not Factor
Liver Metastases – The Future 3
CRC
• Response Rate to Cytotoxic with Biologic
– Up to 50%
• Portal Vein Embolization
– Induces Increase in Volume of the Liver
– Increases the Function
• Regeneration
– 2-4 Weeks in Normal Liver
– 6-8 Weeks for Diabetics and Cirrhotics
Liver Metastases- The Future 4
CRC
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Stage Resection
For Bilateral Lobe Involvement
Chemo- Excise From one Lobe
PVE – Liver Regenaration
Resect from Other Lobe
Survival 40%
80% of Liver Volume can be Resected
Use 3-D CT Volumetry
Surgical Mortality .8%
Liver Metastases
Prevention?
• Stage 2 and 3 CRC
• Hepatic and Regional Chemo Before Surgery
• Randomized, No significant Morbidity
• Time to Liver Mets 16 vs 8 mos.
• Incidence 20.6 vs 28.3
• Disease Free Survival 74vs 58.1 (3 yr)
• Overall 87.7 vs 75.7
• No Benefit for Stage 2
Xu et al. Ann Surg. 2007; 245:583-90
Liver Metastases
Gastric Cancer
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Hepatic Metasectomy done Rarely
Isolated Liver Involvement Rare (.5%)
Long Term Survival is Rare
Non-RandomIzed Series 37 patients -HAI
– 5 FU chemo
– Gastrectomy and HAI
– Better Response
– But No Increase Survival
Ojima et Al. World J Surg. 2007; 5: 70
Liver Metastases
Final Word
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Screen, Screen, Screen for CRC
Polypectomy may be Preventive
Early Cancers are Curable
Have you Had Your Colonoscopy?
• Thank You