1. Liver Metastases Jean-Bernard Poulard MD, MBA, FACS Mount Sinai School of Medicine Queens Hospital Center Jamaica, NY

2. Liver Metastases

3. 30 Years Ago, Considered Incurable

4. Liver 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

5. Liver 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)

6. Liver Mets- Extant of Problem Demographics of Colorectal Cancer Other Gastro-Intestinal Cancers Other Sites Sites Where Treatment Benefits Sites with No Benefit

7. Liver Metastases Practical Considerations Function Accessability Resectability Technical Considerations (Support) Equipment and Machinery Surgical and Interventional Expertise Critical Care

8. Liver Mets -Metastasectomy Indications Tissue Diagnosis Size and Number and Lobes Timing Chemo Pre-Resection? Risks Morbidity and Mortality Outcome

9. Liver Mets - Metastasectomy Extra-Hepatic Disease: Containdication? Used to Be But if Extra-hepatic and Mets Resectable If R 0 Possible – 5 yr 29-38% (Elias et al, BJS 2003; 90: 567-74)

10. Liver 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

11. 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

12. Liver Metastases-Ablation 1 Indications Modalities –Intratumoral, Cryo, Radiation, Thermal Common Attributes Degree of Invasiveness

13. Liver 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

14. 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?

15. 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

16. Liver Metastases Thermal Ablation 1 Modalities –Radiofrequency Ablation –Laser and Microwaves (Europe) Limitations –Control of Margin –Specificity of Tissue Damage Advantage –Percutaneous Approach

17. Liver Metastases Radiofrequency Generator

18. 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

19. Liver Metastases- Recommendations 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

20. 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

21. 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

22. 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

23. Liver Metastases- The Future 4 CRC 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%

24. 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

25. Liver Metastases Gastric 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 Survival Ojima et Al. World J Surg. 2007; 5: 70

26. Liver Metastases Final Word Screen, Screen, Screen for CRC Polypectomy may be Preventive Early Cancers are Curable Have you Had Your Colonoscopy? Thank You