Liver MetastasesLiver Metastases

Jean-Bernard Poulard MD, MBA, FACSJean-Bernard Poulard MD, MBA, FACSMount Sinai School of MedicineMount Sinai School of Medicine

Queens Hospital CenterQueens Hospital CenterJamaica, NYJamaica, NY

Liver MetastasesLiver Metastases

Liver MetastasesLiver Metastases

• 30 Years Ago, Considered Incurable

Liver MetastasisLiver Metastasis

• 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- BiologyLiver Metastases- Biology

• 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 ProblemLiver Mets- Extant of Problem

• Demographics of Colorectal Cancer

• Other Gastro-Intestinal Cancers

• Other Sites

• Sites Where Treatment Benefits

• Sites with No Benefit

Liver MetastasesLiver MetastasesPractical ConsiderationsPractical Considerations

• Function

• Accessability

• Resectability

• Technical Considerations (Support)

• Equipment and Machinery

• Surgical and Interventional Expertise

• Critical Care

Liver Mets -MetastasectomyLiver Mets -Metastasectomy

• Indications• Tissue Diagnosis• Size and Number and Lobes• Timing• Chemo Pre-Resection?• Risks• Morbidity and Mortality• Outcome

Liver Mets - MetastasectomyLiver Mets - Metastasectomy

• 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-HAILiver Metastases-HAI

• Rationale for Hepatic Artery Infusion– Not Amenable to Excision

• 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 2Liver 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 1Liver Metastases-Ablation 1

• Indications

• Modalities– Intratumoral, Cryo, Radiation, Thermal

• Common Attributes

• Degree of Invasiveness

Liver Metastases- IntratumoralLiver Metastases- Intratumoral

• 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 - CryoablationLiver 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- RadiationLiver 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 Liver Metastases Thermal Ablation 1Thermal Ablation 1

• Modalities– Radiofrequency Ablation– Laser and Microwaves (Europe)

• Limitations– Control of Margin– Specificity of Tissue Damage

• Advantage– Percutaneous Approach

Liver MetastasesLiver Metastases

• Radiofrequency Generator

Liver Metastases -RFALiver 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 Metastases- Liver Metastases- RecommendationsRecommendations

• 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 FutureLiver Metastases- The FutureCRCCRC

• 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 2Liver Metastasis- The Future 2CRCCRC

• 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 3Liver Metastases – The Future 3CRCCRC

• 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 4Liver Metastases- The Future 4CRCCRC

• 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 MetastasesLiver MetastasesPrevention?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 2Xu et al. Ann Surg. 2007; 245:583-90

Liver MetastasesLiver MetastasesGastric CancerGastric Cancer

• 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 SurvivalOjima et Al. World J Surg. 2007; 5: 70

Liver MetastasesLiver MetastasesFinal WordFinal Word

• Screen, Screen, Screen for CRC

• Polypectomy may be Preventive

• Early Cancers are Curable

• Have you Had Your Colonoscopy?

• Thank You