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Istituto Nazionale Tumori - Milano

Istituto Nazionale Tumori - Milano. Ri-resection of colorectal liver metastases: the experience of INT-Milan. Liver metastases from colorectal cancer A multidisciplinary approach. Role of Surgical Resection.

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Istituto Nazionale Tumori - Milano

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  1. Istituto Nazionale Tumori - Milano Ri-resection of colorectal liver metastases: the experience of INT-Milan

  2. Liver metastases from colorectal cancer A multidisciplinary approach Role of Surgical Resection • No existing treatment other than surgery can result in long term survival and even in cure [Nordlinger, JCO 2002] • Long survivals are now observed after resection of large or multiple metastases, where surgery would have been refused some years ago [Azulay, Bismuth, Ann.Surg 2002]

  3. Resection of liver metastases from colorectal cancer INT experience 1996-2004 40 % OS 20 % DFS Patients at risk OS 110 71 47 38 25 15 4 211 171 DFS 61 35 23 17 13 9 2 211 116 211 patients: median follow-up 46 months

  4. [Nordlinger, Cancer 1996] OS DFS 28% 15% [Fong, Ann Surg 1999] 37% 22% Surgical resection of colorectal liver metastases: Long-term results 1568 patients French Multicentric Study, 1968-1990 1001 patients MSKCC, 1985-1998

  5. Recurrence after surgical resection • Recurrence is observed in 60-70% of patients after liver resection of liver mets • Some patients, who recur after liver resection, can undergo repeat resection with apparently similar benefit

  6. Studies on repeated hepatic resection for recurrent colorectal liver metastases

  7. Complication rate after liver ri-resection Mortality 0-5 % Morbidity25 % • Postoperative ascites 5-10 % • Bile leak 3 % • Liver failure 1-5 % • Haemorrage 1-2 % • Infections 1-6 % • Pleural effusion / pneumonia 5-10 % • Pulmonary embolism 2 % [Nordlinger, 1994; Scheele, 1995; Adam 1997; Fong 2002]

  8. Repeated hepatic resection for recurrent liver metastases INT experience 1996-2004

  9. Repeated hepatic resection for recurrent liver metastases INT experience 1996-2004 OVERALL SURVIVAL 40 % 48% 20 % Patients at risk OS 21 16 11 11 6 21 21 patients: median follow-up 48 months

  10. Repeated hepatic resection for recurrent liver metastases INT experience 1996-2004 DISEASE-FREE SURVIVAL 40 % 19% 20 % Patients at risk DFS 21 10 8 4 21 patients: median follow-up 48 months

  11. Ri-resection of liver metastases a) Ri-resection for liver recurrence • Portal vein embolization (PVE) and two-stage hepatectomy • Combined intraoperative approach withRF ablation • Pre-operative chemotherapy (neoadjuvant) b) “Salvage resection” for ablation failures • Increasing indication

  12. Combined intraoperative approach to colorectal liver metastases Resection • rule out of extrahepatic disease • intraoperative liver ultrasound • histology, grading, biological markers + Radiofrequency • treatment of histologically-proven unresectable associated mets

  13. Combined intraoperative approach to colorectal liver metastases Multiple liver metastases from colorectal cancer 68 years old man 2/2001 S8 segmentectomy Postoperative CT 2/2002 multiple liver recurrence (S2-3-4-6-7) Treatment: S2-S3-S6-S7 wedge-segmentectomy (6 nodules) intraoperative radiofrequency (S4: 2 nodules) Outcome: patient alive and well 6 months later

  14. Patients characteristics (INT 2000-2004)

  15. Resection + RF in colorectal liver metastases INT experience 2000-2004 Results: survival 25 patients Median follow-up 11 months

  16. Resection + RF in colorectal liver metastases Conclusions based on INT experience • Radiofrequency techniques added to liver resection in case of multifocal disease could extend indication for surgical approach • Residual metastases (< 3 nodules, < 2 cm) could be the best candidates for intraoperative RF • Patients selection could improve cost-effectiveness

  17. Resection of liver metastases “Salvage resection” for ablation failures

  18. Resection of liver metastases “Salvage resection” for ablation failures

  19. Surgical resection of liver metastases: new promises How to decrease post-operative recurrence ? • Post-operative chemotherapy Sistemic vs locoregional with hepatic artery infusion (HAI) • Post-operative immunotherapy

  20. Vaccination with HSPPC-96 in patients withliver metastases from colorectal carcinoma OVERALL SURVIVAL 51% Patients at risk 29 28 26 23 23 22 17 16 13

  21. Vaccination with HSPPC-96 in patients withliver metastases from colorectal carcinoma DISEASE FREE SURVIVAL 25% Patients at risk 29 25 15 13 12 10 7 7 6

  22. Vaccination with HSPPC-96 in patients withliver metastases from colorectal carcinoma OVERALL SURVIVAL Immune responders Immune non-responders p < 0.0001 Patients at risk 17 17 17 17 17 17 14 14 11 Immune responders Immune non-responders 12 9 6 5 3 2 2 11 6

  23. Vaccination with HSPPC-96 in patients withliver metastases from colorectal carcinoma DISEASE FREE SURVIVAL Immune responders Immune non-responders p < 0.0001 Patients at risk 17 16 14 12 11 9 7 7 6 Immune responders Immune non-responders 12 1 1 1 9 1

  24. Conclusions • Vaccination of patients with liver metastases of CRC with autologous HSPPC-96 is feasible and safe • Approximately 60% of patients developed a T-cell mediated response to colorectal carcinoma antigens • Both OS and DFS were longer in T cell responding than in non-responding subjects, independently from other prognostic factors

  25. Surgical treatment of colorectal liver metastases: recent advances and multidisciplinary approach • Ask for surgical consultation before decisions on treatment plan • As long as surgery is curative (R0), resect as many metastases as possible • Add radiofrequency ablation as a complementary technique during surgery within controlled clinical trials • Resect, if possible, any case showing tumor downstaging after chemotherapy

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