Liver Metastases

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

2. Liver Metastases

3. Liver Metastases • 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 MetastasesPractical 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 R0 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 FutureCRC • 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 2CRC • 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 3CRC • 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 4CRC • 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 MetastasesPrevention? • 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 MetastasesGastric 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 MetastasesFinal Word • Screen, Screen, Screen for CRC • Polypectomy may be Preventive • Early Cancers are Curable • Have you Had Your Colonoscopy? • Thank You