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Management Of Liver   M E T A S T A S I S   Patient Selection
Management Of Liver   M E T A S T A S I S   Patient Selection
Management Of Liver   M E T A S T A S I S   Patient Selection
Management Of Liver   M E T A S T A S I S   Patient Selection
Management Of Liver   M E T A S T A S I S   Patient Selection
Management Of Liver   M E T A S T A S I S   Patient Selection
Management Of Liver   M E T A S T A S I S   Patient Selection
Management Of Liver   M E T A S T A S I S   Patient Selection
Management Of Liver   M E T A S T A S I S   Patient Selection
Management Of Liver   M E T A S T A S I S   Patient Selection
Management Of Liver   M E T A S T A S I S   Patient Selection
Management Of Liver   M E T A S T A S I S   Patient Selection
Management Of Liver   M E T A S T A S I S   Patient Selection
Management Of Liver   M E T A S T A S I S   Patient Selection
Management Of Liver   M E T A S T A S I S   Patient Selection
Management Of Liver   M E T A S T A S I S   Patient Selection
Management Of Liver   M E T A S T A S I S   Patient Selection
Management Of Liver   M E T A S T A S I S   Patient Selection
Management Of Liver   M E T A S T A S I S   Patient Selection
Management Of Liver   M E T A S T A S I S   Patient Selection
Management Of Liver   M E T A S T A S I S   Patient Selection
Management Of Liver   M E T A S T A S I S   Patient Selection
Management Of Liver   M E T A S T A S I S   Patient Selection
Management Of Liver   M E T A S T A S I S   Patient Selection
Management Of Liver   M E T A S T A S I S   Patient Selection
Management Of Liver   M E T A S T A S I S   Patient Selection
Management Of Liver   M E T A S T A S I S   Patient Selection
Management Of Liver   M E T A S T A S I S   Patient Selection
Management Of Liver   M E T A S T A S I S   Patient Selection
Management Of Liver   M E T A S T A S I S   Patient Selection
Management Of Liver   M E T A S T A S I S   Patient Selection
Management Of Liver   M E T A S T A S I S   Patient Selection
Management Of Liver   M E T A S T A S I S   Patient Selection
Management Of Liver   M E T A S T A S I S   Patient Selection
Management Of Liver   M E T A S T A S I S   Patient Selection
Management Of Liver   M E T A S T A S I S   Patient Selection
Management Of Liver   M E T A S T A S I S   Patient Selection
Management Of Liver   M E T A S T A S I S   Patient Selection
Management Of Liver   M E T A S T A S I S   Patient Selection
Management Of Liver   M E T A S T A S I S   Patient Selection
Management Of Liver   M E T A S T A S I S   Patient Selection
Management Of Liver   M E T A S T A S I S   Patient Selection
Management Of Liver   M E T A S T A S I S   Patient Selection
Management Of Liver   M E T A S T A S I S   Patient Selection
Management Of Liver   M E T A S T A S I S   Patient Selection
Management Of Liver   M E T A S T A S I S   Patient Selection
Management Of Liver   M E T A S T A S I S   Patient Selection
Management Of Liver   M E T A S T A S I S   Patient Selection
Management Of Liver   M E T A S T A S I S   Patient Selection
Management Of Liver   M E T A S T A S I S   Patient Selection
Management Of Liver   M E T A S T A S I S   Patient Selection
Management Of Liver   M E T A S T A S I S   Patient Selection
Management Of Liver   M E T A S T A S I S   Patient Selection
Management Of Liver   M E T A S T A S I S   Patient Selection
Management Of Liver   M E T A S T A S I S   Patient Selection
Management Of Liver   M E T A S T A S I S   Patient Selection
Management Of Liver   M E T A S T A S I S   Patient Selection
Management Of Liver   M E T A S T A S I S   Patient Selection
Management Of Liver   M E T A S T A S I S   Patient Selection
Management Of Liver   M E T A S T A S I S   Patient Selection
Management Of Liver   M E T A S T A S I S   Patient Selection
Management Of Liver   M E T A S T A S I S   Patient Selection
Management Of Liver   M E T A S T A S I S   Patient Selection
Management Of Liver   M E T A S T A S I S   Patient Selection
Management Of Liver   M E T A S T A S I S   Patient Selection
Management Of Liver   M E T A S T A S I S   Patient Selection
Management Of Liver   M E T A S T A S I S   Patient Selection
Management Of Liver   M E T A S T A S I S   Patient Selection
Management Of Liver   M E T A S T A S I S   Patient Selection
Management Of Liver   M E T A S T A S I S   Patient Selection
Management Of Liver   M E T A S T A S I S   Patient Selection
Management Of Liver   M E T A S T A S I S   Patient Selection
Management Of Liver   M E T A S T A S I S   Patient Selection
Management Of Liver   M E T A S T A S I S   Patient Selection
Management Of Liver   M E T A S T A S I S   Patient Selection
Management Of Liver   M E T A S T A S I S   Patient Selection
Management Of Liver   M E T A S T A S I S   Patient Selection
Management Of Liver   M E T A S T A S I S   Patient Selection
Management Of Liver   M E T A S T A S I S   Patient Selection
Management Of Liver   M E T A S T A S I S   Patient Selection
Management Of Liver   M E T A S T A S I S   Patient Selection
Management Of Liver   M E T A S T A S I S   Patient Selection
Management Of Liver   M E T A S T A S I S   Patient Selection
Management Of Liver   M E T A S T A S I S   Patient Selection
Management Of Liver   M E T A S T A S I S   Patient Selection
Management Of Liver   M E T A S T A S I S   Patient Selection
Management Of Liver   M E T A S T A S I S   Patient Selection
Management Of Liver   M E T A S T A S I S   Patient Selection
Management Of Liver   M E T A S T A S I S   Patient Selection
Management Of Liver   M E T A S T A S I S   Patient Selection
Management Of Liver   M E T A S T A S I S   Patient Selection
Management Of Liver   M E T A S T A S I S   Patient Selection
Management Of Liver   M E T A S T A S I S   Patient Selection
Management Of Liver   M E T A S T A S I S   Patient Selection
Management Of Liver   M E T A S T A S I S   Patient Selection
Management Of Liver   M E T A S T A S I S   Patient Selection
Management Of Liver   M E T A S T A S I S   Patient Selection
Management Of Liver   M E T A S T A S I S   Patient Selection
Management Of Liver   M E T A S T A S I S   Patient Selection
Management Of Liver   M E T A S T A S I S   Patient Selection
Management Of Liver   M E T A S T A S I S   Patient Selection
Management Of Liver   M E T A S T A S I S   Patient Selection
Management Of Liver   M E T A S T A S I S   Patient Selection
Management Of Liver   M E T A S T A S I S   Patient Selection
Management Of Liver   M E T A S T A S I S   Patient Selection
Management Of Liver   M E T A S T A S I S   Patient Selection
Management Of Liver   M E T A S T A S I S   Patient Selection
Management Of Liver   M E T A S T A S I S   Patient Selection
Management Of Liver   M E T A S T A S I S   Patient Selection
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Management Of Liver M E T A S T A S I S Patient Selection

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Liver metastases are malignant tumors that originated at sites remote from the liver and spread to the liver via the bloodstream.

Liver metastases are malignant tumors that originated at sites remote from the liver and spread to the liver via the bloodstream.

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  • 1. Management of Liver Metastasis: Patient Selection S K Mathur MS,FACS Sr Consultant Surgeon Surgical Gastroenterology HPB Surgery &amp; Liver Transplantation <ul><li>Wockhardt hospitals,Mumbai </li></ul>
  • 2. Management of Liver Metastasis: Patient Selection <ul><li>Hepatic resection of liver metastases: </li></ul><ul><li>remains the preferred therapy for potential cure </li></ul><ul><li>The overall 5-year survival rates : </li></ul><ul><li>- with R0 resection 35%–58% </li></ul><ul><li>Chemotherapy: Neoadjuvant or Adjuvant </li></ul><ul><li>Local Ablative therapies </li></ul><ul><li>Use of other adjunctive and adjuvant approaches: </li></ul><ul><li>- to expanding the criteria for resectability </li></ul><ul><li>of patients with colorectal metastasis </li></ul>
  • 3. Management of Liver Metastasis: Patient Selection <ul><li>General criteria for fitness </li></ul><ul><li>Specific Criteria that decides: </li></ul><ul><li>the outcome in terms of: </li></ul><ul><li>- Risk of recurrence </li></ul><ul><li>- Survivals: Disease free and overall </li></ul><ul><li>Anatomical criteria for resectability </li></ul>
  • 4. Management of Liver Metastasis: Patient Selection <ul><li>Specific Criteria: </li></ul><ul><li>Also depends on nature of Primary tumor </li></ul><ul><li>Colorectal malignancy </li></ul><ul><li>Neuro endocrine tumor (NET) </li></ul><ul><li>Non-colorectal / Non NET: Site &amp; type </li></ul>
  • 5. Management of Liver Metastasis: Patient Selection <ul><li>Selection Criteria- Therapy specific: </li></ul><ul><li>Resection: - Primary </li></ul><ul><li>- re-resection </li></ul><ul><li>Ablation </li></ul><ul><li>Combination </li></ul><ul><li>Chemotherapy- Neoadjuvan or Adjuvant </li></ul>
  • 6. Management of Liver Metastasis: Patient Selection <ul><li>Obviously non resectable: </li></ul><ul><li>- Extrahepatic disease at multiple sites </li></ul><ul><li>- uncontrolled Primary </li></ul><ul><li>- Tumor proximity to major hepatic vessels : </li></ul><ul><li>precluding margin –ve resection </li></ul><ul><li>Selection criteria for Resection: </li></ul><ul><li>- Size of liver lesions: &lt;5 cm v/s &gt;5cm </li></ul><ul><li>- number of lesions : &lt; 5 v/s &gt;5 </li></ul><ul><li>- distribution of lesions: uni v/s bi lobar </li></ul><ul><li>- Vol. of residual liver: adequate / &lt;30% </li></ul>Ann Surg Oncol 2004
  • 7. Management of Liver Metastasis: Patient Selection <ul><li>Grey zone for resectability: </li></ul><ul><li>Resectable liver met in presence of: </li></ul><ul><li>- Extrahepatic disease: </li></ul><ul><li>e.g in colorectal Carcinoma </li></ul><ul><li>-resectable Pulmonary metastasis </li></ul><ul><li>-hepatic hilar LN </li></ul><ul><li>- R0 resection not possible: </li></ul><ul><li>- resection margin &lt;1cm </li></ul><ul><li>- cytoreduction: NET </li></ul><ul><li>- Asymptomatic unknown / uncontrolled primary </li></ul>
  • 8. Management of Liver Metastasis: Patient Selection <ul><li>Other selection criteria for Resection: </li></ul><ul><li>based on Predictive factors for outcome: </li></ul><ul><li>- time from primary tumor to metastases </li></ul><ul><li>- tumor Grade </li></ul><ul><li>- nodal status of primary </li></ul><ul><li>- CEA levels </li></ul><ul><li>- number of liver lesions </li></ul><ul><li>- size of liver lesions </li></ul><ul><li>- resection margin status </li></ul>
  • 9. Clinical score for predicting recurrence after hepatic resection for metastatic colorectal cancer: analysis of 1001 consecutive cases. Fong Y, Fortner J, Sun RL, et al. Ann Surg. 1999. <ul><li>For the CRS, each of 5 clinical criteria is assigned 1 point: </li></ul><ul><li>1) node-positive primary </li></ul><ul><li>2)&lt;12 month disease-free interval </li></ul><ul><li>3) &gt;1 liver tumors </li></ul><ul><li>4) largest tumor &gt;5 cm </li></ul><ul><li>5) CEA &gt;200 ng/mL. </li></ul>
  • 10. Clinical score for predicting recurrence after hepatic resection for metastatic colorectal cancer: analysis of 1001 consecutive cases. Fong Y, Fortner J, Sun RL, et al. Ann Surg. 1999.
  • 11. Analysis of prognostic factors influencing long-term survival after hepatic resection for metastatic colorectal cancer <ul><li>The retrospective analysis of 297 liver resections for colorectal metastases </li></ul><ul><li>The multivariate analysis showed three independent negative prognostic factors: </li></ul><ul><li>G3 or G4 grade, </li></ul><ul><li>CEA &gt;5 ng/ml, </li></ul><ul><li>high MSKCC-CRS: &gt;2 </li></ul><ul><li>CONCLUSIONS: in the presence of negative prognostic factors enrollment of patients in trials exploring new adjuvant treatments is suggested to improve the outcome after surgery . </li></ul>Arru M ,et al Italy, World J Surg. 2008
  • 12. A Nomogram for Predicting Disease-specific Survival After Hepatic Resection for Metastatic Colorectal Cancer Kattan MW, Gönen M, William R. Jarnagin WR, DeMatteo R, Michael D&apos;Angelica M, Martin Weiser M, Leslie H. Blumgart LS, Fong Y, <ul><li>  </li></ul>Based on the Cox proportional hazards regression model, a nomogram was constructed (Fig. 2). A version of this nomogram that can be downloaded and installed on a pocket digital assistant (PDA) for routine use can be found at the follow Internet site: www.nomograms.org . It has a bootstrap-corrected concordance index of 0.612 and seems well calibrated Ann Surg.  2008;247(2):282-287
  • 13. A Nomogram for Predicting Disease-specific Survival After Hepatic Resection for Metastatic Colorectal Cancer <ul><li>patients with hepatic metastases are not homogeneous with respect to risk of recurrence and death, following hepatectomy. </li></ul><ul><li>Individual patient decision making requires better tools for assessing prognosis to provide patient selection for surgery </li></ul><ul><li>When refit to those patients used in the original CRS </li></ul><ul><li>the nomogram predicted more accurately than did the Fong score when both were applied to the same validation dataset. </li></ul>Ann Surg.  2008;247(2):282-287
  • 14. Criteria for Resectability of Colorectal Liver Metastases <ul><li>Old Paradigm: Traditional Factors Associated With Resectability : </li></ul><ul><li>Tumor Number 3-4 ? </li></ul><ul><li>Tumor Size &lt; /= 3cm ? </li></ul><ul><li>Surgical Margin &gt;1 cm? Microscopic negative margin more important than width </li></ul><ul><li>No extrahepatic Disease ? </li></ul><ul><li>Earlier reports of 5Yrs Survival: 0 – 20%? </li></ul>Pawlik, T. M. et al. Oncologist 2008;13:51-64
  • 15. Management of Liver Metastasis: Patient Selection Pawlik, T. M. et al. Oncologist 2008;13:51-64
  • 16. Pawlik, T. M. et al. Oncologist 2008;13:51-64 Survival following hepatic resection of colorectal metastases is not associated with the width of the negative surgical margin as long as the margin is completely microscopically negative
  • 17. Results of R0 Resection for Colorectal Liver Metastases Associated With Extrahepatic Disease Elias D et al ( France) Ann Surg Oncol 2004 <ul><li>Survival of patients with R0 resection </li></ul>Multivariate Analysis of Prognostic Factors statistically significant negative factors in the Cox model : -presence of multiple sites of extrahepatic disease (including peritoneal carcinomatosis; P = .04) -more than five LMs ( P = .02). Conclusions: EHD in CRC patients with liver metastases should no longer be considered as a contraindication to hepatectomy.
  • 18. Management of Liver Metastasis: Patient Selection <ul><li>Redefining the resectability of colorectal liver metastasis : </li></ul><ul><li>No more defined by strict criteria on: numbers, size and distribution of liver metastases </li></ul><ul><li>The determination of resectability is now based on: </li></ul><ul><li>- whether it is possible to remove all known disease </li></ul><ul><li>- while leaving behind an adequate functional </li></ul><ul><li>remnant liver </li></ul>Choti MA. Current Colorectal Cancer reports 2008
  • 19. New paradigm:4 main Criteria for Resectability of Colorectal Liver Metastases <ul><li>An R0 resection of both the intra- and extrahepatic disease sites must be feasible. </li></ul><ul><li>At least two adjacent liver segments need to be spared. </li></ul><ul><li>Vascular inflow and outflow, as well as biliary drainage to the remaining segments, must be preserved. </li></ul><ul><li>The volume of the liver remaining after resection (i.e., the future liver remnant) must be adequate </li></ul>Pawlik, T. M. et al. Oncologist 2008;13:51-64
  • 20. New paradigm:4 main Criteria for Resectability of Colorectal Liver Metastases <ul><li>The volume of the liver remaining after resection (i.e., the future liver remnant) must be adequate. </li></ul><ul><li>which usually means at least </li></ul><ul><li>20% of the total estimated liver volume for normal parenchyma:, </li></ul><ul><li>30%–60% if the liver is injured by chemotherapy, steatosis, or hepatitis </li></ul><ul><li>40%–70% in the presence of cirrhosis, </li></ul><ul><li>depending on the degree of underlying hepatic dysfunction </li></ul>[Ferrero A,et al World J Surg 2007; ]
  • 21. Strategies to increase the Resectability <ul><li>increase/preserve hepatic reserve, </li></ul><ul><li>- Portal Vein Embolisation: inadequate FLR </li></ul><ul><li>- Two- stage resection: bilobar disease </li></ul><ul><li>combined local therapy: Resection Plus RFA </li></ul><ul><li>- Resect- larger lesion </li></ul><ul><li>- Ablate- smaller lesions </li></ul><ul><li>decrease tumor size: Chemotherapy </li></ul>
  • 22. Stratigies to increase the Resectability Two- stage heptectomy <ul><li>Indication: unresectable bilobar disease due to inadeuate FLR </li></ul><ul><li>First stage: resect Mets in FLR PVE </li></ul><ul><li>2 nd Stage resection after 3-4weeks </li></ul><ul><li>Results: </li></ul><ul><li>-Adam et al. 3-year survival rate of 35% </li></ul><ul><li>-Jaeck et al. 1- and 3-year survival rates of 70.0% and 54.4% </li></ul>Ann Surg 2000 &amp; Ann Surg 2004
  • 23. Strategies to increase the Resectability <ul><li>increase/preserve hepatic reserve, </li></ul><ul><li>- Portal Vein Embolisation: inadequate FLR </li></ul><ul><li>- Two- stage resection: bilobar disease </li></ul><ul><li>combined local therapy: Resection Plus RFA </li></ul><ul><li>Decrease tumor size: </li></ul><ul><li>- with neo-adjuvant chemotherapy </li></ul><ul><li>Adam et al. reported that rescue surgery for un-resectable colorectal liver metastases downsized by chemotherapy resulted in a 5-year survival rate of 33% </li></ul>Ann Surg 2004
  • 24. Management of Liver Metastasis: Patient Selection <ul><li>Contraindication for hepatic resection </li></ul><ul><li>Patients with extensive extrahepatic disease </li></ul><ul><li>those who progress on systemic chemotherapy </li></ul>
  • 25. Management of Liver Metastasis: Patient Selection for re-resection <ul><li>After &amp;quot;curative&amp;quot; hepatic metastasectomy for colorectal cancer, 60% will develop local, regional, or distant recurrence. </li></ul><ul><li>85% of recurrences occur within the first 30 months of the original resection </li></ul><ul><li>30% of recurrences are confined to the liver allowing for consideration of repeat hepatic resections or ablation procedures </li></ul><ul><li>repeat resections are associated with a 5-year survival rate of 20% to 30%. </li></ul>Cancer Control.  2006
  • 26. Management of Liver Metastasis: Patient Selection in CRC Liver Metastases <ul><li>Chemotherapy: Indications at presentation </li></ul><ul><li>Multiple metastases and stage IV disease </li></ul><ul><li>Marginally unresectable L M: </li></ul><ul><li>size, number, </li></ul><ul><li>or location close to vascular structures </li></ul><ul><li>- to down size the metastases </li></ul><ul><li>response could help achieve Ro resection </li></ul>Choti MA. Current Colorectal Cancer reports 2008
  • 27. Management of Liver Metastasis: Patient Selection for Local Ablation in Colorectal Liver Metastases <ul><li>Indication for ablation is in patients: </li></ul><ul><li>who do not meet the criteria for resectability </li></ul><ul><li>but are candidates for liver-directed therapy based upon the presence of liver-only disease. </li></ul><ul><li>complete margin-negative ablation can be achieved </li></ul>
  • 28. Predictors of Survival After Radiofrequency Thermal Ablation of Colorectal Cancer Metastases to the Liver: A Prospective Study <ul><li>Patients with the dominant lesion less than 5 cm in diameter had a median survival of 34 months v/s 21 months for lesions greater than 5 cm ( P = .03). </li></ul><ul><li>Survival approached significance for patients with &lt;3 tumors versus &gt;3 tumors (29 v 22 months; P = .09). </li></ul>Journal of Clinical Oncology, 2005
  • 29. Management of Liver Metastasis: Patient Selection for LM from NET <ul><li>5 yrs survival: -without resection: 40% </li></ul><ul><li>- after Liver resection: 60% </li></ul><ul><li>Indications Liver resection: </li></ul><ul><li>when Ro resection is possible </li></ul><ul><li>Palliative cytoreduction ( 90% of tumor): </li></ul><ul><li>to improve quality of life </li></ul><ul><li>- after failure of medical therapy to control </li></ul><ul><li>endocrinopathy-related symptoms </li></ul><ul><li>- pain &amp; discomfort due to massive size </li></ul><ul><li>(non-functional tumors) </li></ul>Mayo Clinic. J Am Coll Surg. 2003 Wisconsin Arch Surg.  2006
  • 30. Treatment of liver metastases from neuroendocrine tumours in relation to the extent of hepatic disease <ul><li>This study identified LM-specific variables that could be used as additional selection criteria for aggressive treatment. </li></ul><ul><li>From 1992 to 2006, 119 patients underwent staging and treatment of LM. </li></ul><ul><li>Three types of LM were identified radiologically: </li></ul><ul><li>Type I: single metastasis </li></ul><ul><li>Type II: isolated metastatic bulk accompanied by smaller deposits </li></ul><ul><li>Type III: disseminated metastatic spread </li></ul>Frilling, A.et al; B. J. S., Feb 2009
  • 31. Treatment of liver metastases from neuroendocrine tumours in relation to the extent of hepatic disease <ul><li>Results: </li></ul><ul><li>Survival rates: 3 yrs 5yrs 10year </li></ul><ul><li>* Entire cohort 76·4% 63·9% 46·5% </li></ul><ul><li>There were significant differences in 5- and 10-year survival between the 3 groups </li></ul><ul><li>* Type I 100% 100% </li></ul><ul><li>* Type II 84% 75 % </li></ul><ul><li>* Type III 51% 29 % </li></ul><ul><li>Conclusion: </li></ul><ul><li>The localization and biological features of LM from NET defines therapeutic management and is predictive of survival </li></ul>Frilling, A.et al; B. J. S., Feb 2009
  • 32. Management of Liver Metastasis: Patient Selection for LM from NET <ul><li>NET Liver Metastasis </li></ul><ul><li>Other Prognostic markers </li></ul><ul><li>Histological grade of Primary: </li></ul><ul><li>G1 &amp;G2 v/s G3 &amp;G4 </li></ul><ul><li>Site of Primary tumor </li></ul>M.D. Anderson Cancer Center Journal of Clinical Oncology , 2008: No Extra hepatic disease World J Surg Oncol. 2006 ;
  • 33. Management of Liver Metastasis: Patient Selection Non Colorectal / Non NET Liver Metastasis <ul><li>5 yrs Survival of Liver Resection according to Primary: </li></ul><ul><li>Genitourinary tract: 42 - 60% </li></ul><ul><li>Soft tissue tumors: 30% </li></ul><ul><li>Breast cancer : 41% </li></ul><ul><li>Upper GI : 15-30% </li></ul><ul><li>Pancreas &lt;15% </li></ul>Adam et al Ann Surg 2006, Harrison et al . Surgery 1997
  • 34. Hepatic Resection for Noncolorectal Nonendocrine Liver Mets Analysis of 1452 Patients and Development of a Prognostic Model :Paul Brousse Hospital Villejuif, France <ul><li>In multivariate analysis, factors associated with poor prognosis were: (all P ≤ 0.02). </li></ul><ul><li>- patient age &gt;60 years </li></ul><ul><li>- non-breast origin </li></ul><ul><li>- melanoma or squamous histology </li></ul><ul><li>- disease-free interval &lt;12 months </li></ul><ul><li>- extrahepatic metastases, </li></ul><ul><li>- R2 resection </li></ul><ul><li>- major hepatectomy </li></ul>Adam et al Ann Surg 2006,
  • 35. Hepatic Resection for Noncolorectal Nonendocrine Liver Mets Analysis of 1452 Patients and Development of a Prognostic Model :Paul Brousse Hospital Villejuif, France <ul><li>A prognostic model based on these factors effectively stratified patients into: </li></ul><ul><li>low-risk (0–3 points): 46% 5-year survival </li></ul><ul><li>mid-risk (4–6 points): 33% 5-year survival </li></ul><ul><li>high-risk (&gt;6 points): &lt;10% 5-year survival groups ( P = 0.0001). </li></ul>Adam et al Ann Surg 2006,
  • 36. Adam et al Ann Surg 2006,
  • 37. Hepatic Resection for Noncolorectal Nonendocrine Liver Mets Analysis of 1452 Patients and Development of a Prognostic Model :Paul Brousse Hospital Villejuif, France <ul><li>Five-Year and Median Survivals for Patients With noncolorectal Nonendocrine Liver Metastases From Individual Primary Tumor Sites Grouped by: </li></ul><ul><li>Favorable (Group 1) : &gt; 33% </li></ul><ul><li>Intermediate (Group 2): 15 – 30% </li></ul><ul><li>Poor Outcomes (Group 3): &lt; 15% </li></ul>Adam et al Ann Surg 2006,
  • 38. Management of Liver Metastasis: Patient Selection Non Colorectal / Non NET Liver Metastasis <ul><li>Favourable Prognostic factors for Relapse Free Survival on multivariate analysis: </li></ul><ul><li>Primary tumor type: metastases from reproductive tract V/s non reproductive tumors (63% v/s 30%) </li></ul><ul><li>Length of disease free interval from the primary tumor ( &gt; 24 months). </li></ul><ul><li>Margin status- R0 resections: </li></ul><ul><li>3 yr survival of 78%. </li></ul>Weitz et al. Ann Surg 2005
  • 39. Management of Liver Metastasis: Patient Selection Non Colorectal / Non NET Liver Metastasis <ul><li>presence of extrahepatic disease prior to or at the time of hepatectomy </li></ul><ul><li>Pre hepatectomy disease progression while on chemotherapy </li></ul>Adam et al Ann Surg 2006,
  • 40. Management of Liver Metastasis: Patient Selection Non Colorectal / Non NET Liver Metastasis <ul><li>Tumor type- GIST </li></ul><ul><li>Imatinib is the first line treatment. </li></ul><ul><li>Resection to be considered if tumor reach maximal response to Imatinib or become resistant to it. </li></ul><ul><li>Disease free interval of &gt; 24months </li></ul><ul><li>Ro Resection should be possible </li></ul><ul><li>5 yr overall survival rates : 30 -70% </li></ul>Antonescu et al,Clin Can Res2005, Demato et al, Ann of Surg Oncology 2002 Adam et al Ann Surg 2006
  • 41. Management of Liver Metastasis: Patient Selection Non Colorectal / Non NET Liver Metastasis <ul><li>Tumor type- Melanoma </li></ul><ul><li>Overall survival of patients treated by complete resection :28 months. </li></ul><ul><li>5 yr survival was 29%. </li></ul><ul><li>In patients treated non operatively survival was only 6 months. </li></ul><ul><li>Extrahepatic disease was not a contraindication for liver resection as long as all disease is resectable . </li></ul>Rose et al. Sydney Melanoma unit 2001
  • 42. Management of Liver Metastasis: Patient Selection Non Colorectal / Non NET Liver Metastasis <ul><li>Tumor type- Breast </li></ul><ul><li>Solitary Liver metastases </li></ul><ul><li>Localised (&gt;2) metastases: </li></ul><ul><li>- resectable by Ro resection </li></ul><ul><li>patients who do not progress while on systemic chemotherapy </li></ul><ul><li>No multiple bone metastasis </li></ul>Elias et al, Am J Surg 2003
  • 43. Management of Liver Metastasis: Patient Selection Non Colorectal / Non NET Liver Metastasis <ul><li>Tumor type- Breast </li></ul><ul><li>Adverse prognostic factors: </li></ul><ul><li>- Receptor negative status. </li></ul><ul><li>- node positive primary. </li></ul><ul><li>- Local recurrence of primary </li></ul><ul><li>- Short disease free survival. </li></ul><ul><li>extrahepatic disease is an exclusion criteria. </li></ul>Elias et al, Am J Surg 2003
  • 44. Management of Liver Metastasis: Patient Selection Non Colorectal / Non NET Liver Metastasis <ul><li>Tumor type- Germ cell tumors </li></ul><ul><li>liver resection for metastatic tumors </li></ul><ul><li>5 yr survival rate : 62% </li></ul><ul><li>Defined three adverse prognostic factors: </li></ul><ul><li>- Pure embryonal cell carcinoma in the primary tumor. </li></ul><ul><li>- Liver metastasis more than 3 cms. in males </li></ul><ul><li>- Presence of viable residual disease after </li></ul><ul><li>chemotherpy. </li></ul>Gholam et al, Cancer 2003
  • 45. Management of Liver Metastasis: Patient Selection Non Colorectal / Non NET Liver Metastasis <ul><li>Conclusion </li></ul><ul><li>Hepatic resection for metastatic NCNN tumors is safe and effective in selected patients </li></ul><ul><li>Primary tumor type </li></ul><ul><li>DFI seem to be the only valid selection parameters. </li></ul><ul><li>R0 resection must be achieved </li></ul>
  • 46. Copyright ©2008 AlphaMed Press Pawlik, T. M. et al. Oncologist 2008;13:51-64 Over the last decade, the criteria for resectability of colorectal liver metastases have been expanded and have undergone a paradigm shift Management of Liver Metastasis: Patient Selection
  • 47. Expanding Criteria for Resectability of Colorectal Liver Metastases Timothy M. Pawlik, Richard D. Schulick, Michael A. Choti John Hopkins <ul><li>Surgical resection is the treatment of choice in patients with colorectal liver metastases, with 5-year survival rates reported in the range of 40%–58%. Over the past 10 years, there has been an impetus to expand the criteria for defining resectability for patients with colorectal metastases. </li></ul><ul><li>In the past, such features as the number of metastases (three to four), the size of the tumor lesion, and a mandatory 1-cm margin of resection dictated who was &amp;quot;resectable.“ </li></ul><ul><li>More recently, the criteria for resectability have been expanded to include any patient in whom all disease can be removed with a negative margin and who has adequate hepatic volume/reserve. </li></ul><ul><li>Specifically, instead of resectability being defined by what is removed, decisions concerning resectability now center around what will remain after resection. </li></ul><ul><li>Under this new paradigm, the number of patients with resectable disease can be expanded by increasing/preserving hepatic reserve (e.g., portal vein embolization, two-stage hepatectomy), combining resection with ablation, and decreasing tumor size (preoperative chemotherapy). </li></ul><ul><li>The criteria for resectability have also expanded to include patients with extrahepatic disease. Rather than being an absolute contraindication to surgery, patients with both intra- and extrahepatic disease should potentially be considered for resection based on strict selection criteria. </li></ul><ul><li>The expansion of criteria for resectability of colorectal liver metastases requires a much more nuanced and sophisticated approach to the patient with advanced disease. </li></ul><ul><li>A therapeutic approach that includes all aspects of multidisciplinary and multimodality care is required to select and treat this complex group of patients. </li></ul>The Oncologist, 2008;
  • 48. Management of Liver Metastasis: Patient Selection <ul><li>It involves: a) multi disciplinary approach </li></ul><ul><li>and b) a correct preoperative planning </li></ul><ul><li>To convert unresectable disease into resectable. </li></ul><ul><li>downsizing the tumor with pre op therapy </li></ul><ul><li>Increasing remnant liver Volume: </li></ul><ul><li>- by doing staged resection </li></ul><ul><li>- pre-op Portal vein embolisation </li></ul><ul><li>Combining ablative therapy with resection </li></ul>
  • 49. Management of Liver Metastasis: Patient Selection: Conclusions <ul><li>Patient selection for management of liver metastases is going to be “Dynamic Process” </li></ul><ul><li>The criteria for resection will get expanded as long as Ro resection can be achieved </li></ul><ul><li>A rational use of “Multi disciplinary approach” </li></ul><ul><li>is important to select a patient for various available therapeutic modalities to be used in a appropriate sequential order with a aim to achieve Ro resection </li></ul>
  • 50. THANK YOU
  • 51. Combination of surgery and chemotherapy and the role of targeted agents in the treatment of patients with colorectal liver metastases: recommendations from an expert panel on behalf of the European Colorectal Metastases Treatment Group Ann. Onc., January 19, 2009; (2009) <ul><li>The past 5 years have seen the clear recognition that the administration of chemotherapy to patients with initially unresectable colorectal liver metastases can increase the number of patients who can undergo potentially curative secondary liver resection. Coupled with this, recent data have emerged that show that perioperative chemotherapy confers a disease-free survival advantage over surgery alone in colorectal cancer (CRC) patients with initially resectable liver disease. The purpose of this paper is to build on the existing knowledge and review the issues surrounding the use of chemotherapy ± targeted agents combined with surgery in the treatment of CRC patients with liver metastases, with a view to providing clinical recommendations. An international panel of 21 experts in colorectal oncology comprising liver surgeons and medical oncologists reviewed the available evidence. In a major change to clinical practice, </li></ul><ul><li>the panel&apos;s recommendation was that the majority of patients with CRC liver metastases should be treated up front with chemotherapy, irrespective of the initial resectability status of their metastases. </li></ul>
  • 52. Management of Liver Metastasis: Patient Selection Non Colorectal / Non NET Liver Metastasis <ul><li>Disease free survival is an effective surrogate for favorable tumor biology. </li></ul><ul><li>Primary tumor type is a important prognostic marker. </li></ul><ul><li>Behavior of the hepatic metastasis is similar to the primary tumor </li></ul><ul><li>venous invasion by the primary or positive nodal status predict adverse prognostic factors after hepatectomy. </li></ul>
  • 53. Hepatic Resection for Noncolorectal Nonendocrine Liver Mets Analysis of 1452 Patients and Development of a Prognostic Model :Paul Brousse Hospital Villejuif, France <ul><li>Hepatic metastases : - solitary in 56% </li></ul><ul><li>- unilateral in 71% (mean diameter, 5.5cm) </li></ul><ul><li>- Extrahepatic metastases were present in 22%. </li></ul><ul><li>The most common primary sites were: </li></ul><ul><li>- breast 32% </li></ul><ul><li>- gastrointestinal 16% </li></ul><ul><li>- urologic 14% </li></ul><ul><li>The most common histologies : </li></ul><ul><li>- adenocarcinoma 60% </li></ul><ul><li>- GIST/sarcoma 13.5% </li></ul><ul><li>- melanoma 13% </li></ul><ul><li>R0 resection was achieved in 83% of patients </li></ul><ul><li>Overall and disease-free survivals at 5 years were 36% and 21% and at 10 years were 23% and 15%, respectively. </li></ul>Adam et al Ann Surg 2006,
  • 54. Proposal of criteria to select candidates with colorectal liver metastases for hepatic resection: comparison of our scoring system to the positive number of risk factors. Nagashima I , Takada T , Adachi M , Nagawa H , Muto T , Okinaga K . <ul><li>Multivariate analysis showed significant and independent prognostic factors for poor survival after hepatectomy (P &lt; 0.05). : </li></ul><ul><li>- multiple tumors </li></ul><ul><li>- largest tumor greater than 5 cm in diameter </li></ul><ul><li>- unresectable extrahepatic metastases </li></ul><ul><li>3 more factors were selected by a stepwise method of Cox regression analysis ( P &lt; 0.20). </li></ul><ul><li>- serosa invasion, </li></ul><ul><li>- local lymph node metastases of primary cancers, </li></ul><ul><li>- and post-operative disease free interval less than 1 year including synchronous hepatic metastasis </li></ul>World J Gastroenterol. 2006
  • 55. Proposal of criteria to select candidates with colorectal liver metastases for hepatic resection: comparison of our scoring system to the positive number of risk factors. Nagashima I , Takada T , Adachi M , Nagawa H , Muto T , Okinaga K . <ul><li>Using these six variables: </li></ul><ul><li>created a new scoring formula to classify patients with colorectal liver metastases. </li></ul><ul><li>CONCLUSION: </li></ul><ul><li>Both, new scoring system and the positive number of significant prognostic factors are useful to classify patients with colorectal liver metastases in the preoperative selection of good candidates for hepatic resection. </li></ul>World J Gastroenterol. 2006
  • 56. Results of R0 Resection for Colorectal Liver Metastases Associated With Extrahepatic Disease Elias D et al ( France) Ann Surg Oncol 2004 <ul><li>From January 1987 to January 2001, 75 patients underwent a complete R0 resection of extrahepatic disease simultaneously with hepatectomy for colorectal liver metastases. </li></ul><ul><li>Compared the survival rates: with that of the patients without extrahepatic disease (n = 219) who underwent an R0 hepatectomy for colorectal LM in the same institution during the same time period </li></ul><ul><li>Analysed prognostic factors for poor outcome </li></ul>
  • 57. Expanding Criteria for Resectability of Colorectal Liver Metastases Timothy M. Pawlik, Richard D. Schulick, Michael A. Choti John Hopkins The Oncologist, 2008; <ul><li>Surgical resection is the treatment of choice in patients with colorectal liver metastases, with 5-year survival rates reported in the range of 40%–58%. Over the past 10 years, there has been an impetus to expand the criteria for defining resectability for patients with colorectal metastases. </li></ul><ul><li>In the past, such features as the number of metastases (three to four), the size of the tumor lesion, and a mandatory 1-cm margin of resection dictated who was &amp;quot;resectable.“ </li></ul><ul><li>More recently, the criteria for resectability have been expanded to include any patient in whom all disease can be removed with a negative margin and who has adequate hepatic volume/reserve. </li></ul><ul><li>Specifically, instead of resectability being defined by what is removed, decisions concerning resectability now center around what will remain after resection. </li></ul><ul><li>Under this new paradigm, the number of patients with resectable disease can be expanded by increasing/preserving hepatic reserve (e.g., portal vein embolization, two-stage hepatectomy), combining resection with ablation, and decreasing tumor size (preoperative chemotherapy). </li></ul><ul><li>The criteria for resectability have also expanded to include patients with extrahepatic disease. Rather than being an absolute contraindication to surgery, patients with both intra- and extrahepatic disease should potentially be considered for resection based on strict selection criteria. The expansion of criteria for resectability of colorectal liver metastases requires a much more nuanced and sophisticated approach to the patient with advanced disease. A therapeutic approach that includes all aspects of multidisciplinary and multimodality care is required to select and treat this complex group of patients. </li></ul>
  • 58. Neuroendocrine hepatic metastases: does aggressive management improve survival Touzios JG , Kiely JM , Pitt SC , Rilling WS , Quebbeman EJ , Wilson SD , Pitt HA . Wisconsin Ann Surg. 2005 <ul><li>hepatic metastases from NET :N =60 </li></ul><ul><li>23 received no aggressive treatment of their liver metastases, </li></ul><ul><li>19 were treated with hepatic resection and/or ablation, </li></ul><ul><li>18 were managed with TACE </li></ul><ul><li>RESULTS: </li></ul><ul><li>Survival Median and 5-year </li></ul><ul><li>* Nonaggressive group 20 months 25% </li></ul><ul><li>* Resection/Ablation group &gt;96 months 72% (P &lt; 0.05) </li></ul><ul><li>* TACE group 50 months 50% </li></ul><ul><li>Patients with more than 50% liver involvement had a poor outcome (P &lt; 0.001). </li></ul><ul><li>CONCLUSIONS: </li></ul><ul><li>-Aggressive management of NET hepatic metastases does improve survival, </li></ul><ul><li>-TACE increases the patient population eligible for this strategy, </li></ul>
  • 59. Hepatic Resection for Noncolorectal Nonendocrine Liver Mets Analysis of 1452 Patients and Development of a Prognostic Model :Paul Brousse Hospital Villejuif, France Adam et al Ann Surg 2006,
  • 60. &nbsp;
  • 61. <ul><li>THANK YOU..! </li></ul>
  • 62. Management of Liver Metastasis: Patient Selection Non Colorectal / Non NET Liver Metastasis <ul><li>R0 resection must be achieved. </li></ul>
  • 63. Comparison with colorectal metastasis <ul><li>Reasons for success of liver resection in colorectal metastasis : two concepts </li></ul><ul><li>- favourable tumor biology, inefficient dissemination into blood stream, and inefficient adhesion molecules. </li></ul><ul><li>- tumor spread by portal vein leads to effective entrapment by the liver, leading to less common extrahepatic disease. </li></ul>
  • 64. COLORECTAL AND NEUROENDOCRINE <ul><li>Hepatic resection is a well established modality. </li></ul><ul><li>Colorectal 3 yr survival rates 30% to 61% and 5 yr survival rates 16% to 51%. </li></ul><ul><li>( Fong et al, 1997, Scheele et al,1995) </li></ul>
  • 65. <ul><li>Neuroendocrine tumors 5 yr survival of 76% with surgical resections. </li></ul><ul><li>( Chamberlain et al 2000) </li></ul><ul><li>The factors governing the outcomes are fairly well demarcated. </li></ul>
  • 66. Issues in NCNN <ul><li>Smaller number of series. </li></ul><ul><li>Inclusion of multiple tumor types in the same series to have a large number of patients to analyze. </li></ul>
  • 67. Series summarizing multiple tumor types <ul><li>Goering et.al.Am J of Surg 183: 384-389, 2002 </li></ul><ul><li>48 patients with liver resection or ablative therapy. </li></ul><ul><li>5 yr survival rate of 39%. </li></ul><ul><li>3 yr survival- Geniourinary- 52%, Soft tissue tumors- 34% vs neuroendocine 91%. </li></ul>
  • 68. Series summarizing multiple tumor types <ul><li>Elias et al, Am.Coll of Surg. 187: 493, 1998. </li></ul><ul><li>147 patients with mets from non colorectal primary. </li></ul><ul><li>Operative mortality of 2%. </li></ul><ul><li>5 yr survival rates: Breast 20%, Testicular 46%, Sarcoma 18%, Gastric 20%. </li></ul>
  • 69. Series summarizing multiple tumor types <ul><li>Laurent et al. World J Surg:25:1532-1536 , 2001. </li></ul><ul><li>39 patients. </li></ul><ul><li>5 year survival for the entire group was 35%. </li></ul><ul><li>However they noted that 5 yr survival was 100% for patients with disease free interval of 24 months or more vs. 10% for patients with disease free interval of less than 24 months </li></ul>
  • 70. The MSKCC Experience <ul><li>Weitz et al 2004. </li></ul><ul><li>Patients from 1981 t0 2002. </li></ul><ul><li>141 patients </li></ul><ul><li>33% had postoperative complications but 30 day mortality was 0. </li></ul><ul><li>3 yr relapse free survival 30%. </li></ul>
  • 71. <ul><li>Prognostic factors: </li></ul><ul><li>Primary tumor type. </li></ul><ul><li>Length of disease free interval from the primary tumor ( &gt; 24 months). </li></ul><ul><li>Margin status- R0 resections had 3 yr survival of 78%. </li></ul>
  • 72. R 0 resection and survival
  • 73. Disease free interval and survival
  • 74. Series focusing on one tumor type- SARCOMAS <ul><li>Demato et al, 2002 Ann of Surg Oncology 9: 831-839. </li></ul><ul><li>56 patients admitted at MSKCC. </li></ul><ul><li>GIST and stromal tumors were the most common types. </li></ul><ul><li>5 yr overall survival rates were 30% </li></ul><ul><li>Disease free interval of less than 24 months was adverse prognostic factor. </li></ul>
  • 75. <ul><li>At present Imatinib is the first line treatment. </li></ul><ul><li>Resection to be considered if tumor reach maximal response to Imatinib or become resistant to it. </li></ul><ul><li>Resection improves survival only if all tumor can be removed. </li></ul><ul><li>( Antonescu et al 2005,Clin Can Res 11: 4812- 4910.) </li></ul>
  • 76. Resection Vs. other treatment for sarcomas
  • 77. DFI and survival for sarcomas
  • 78. Melanomas <ul><li>Hepatic mets are diagnosed in 10 to 20% of cases of Stage 4 melanomas. </li></ul><ul><li>Rose et al Sydney Melanoma unit 2001. </li></ul><ul><li>26204 patients of melanoma. </li></ul><ul><li>1750 patients had liver mets ( 6.7%) </li></ul><ul><li>34 underwent an exploration out of which only 24 had resection. </li></ul><ul><li>Out of the 10 non resected patients the mean survival was only 4.4 months. </li></ul>
  • 79. <ul><li>Overall survival of patients treated by complete resection was 28 months. </li></ul><ul><li>5 yr survival was 29%. </li></ul><ul><li>In patients treated non operatively survival was only 6 months. </li></ul><ul><li>Extrahepatic disease was not a contraindication for liver resection as long as all disease is resectable. </li></ul>
  • 80. Management of Liver Metastasis: Patient Selection Non Colorectal / Non NET Liver Metastasis <ul><li>Prognostic factors </li></ul>Weitz et al. Ann Surg 2005
  • 81. <ul><li>Although no Level 1 evidence exists that liver resection in metastatic Ca Breast improves survival, more and more recently published series show 5 yr survival rates of 34% to 61%. </li></ul><ul><li>Elias et al, Am J Surg 2003 185:158-164. </li></ul><ul><li>Vlastos et al, 2004, Ann of Surg Onco. 11 :869-874. </li></ul>Breast
  • 82. <ul><li>This is when compared to patients of liver metastasis who receive only chemotherapy --- rarely if ever survive for more than 5 years. </li></ul>
  • 83. Ablation in Breast metastases <ul><li>More study is required within the era of the latest systemic therapies but </li></ul><ul><li>Ablation compares well with the surgical literature </li></ul><ul><ul><li>Median 32 months </li></ul></ul><ul><ul><li>5-yr survival of 37% in selected patients </li></ul></ul><ul><li>And can be readily combined with systemic therapy </li></ul>
  • 84. <ul><li>Adverse prognostic factors: </li></ul><ul><li>- Receptor negative status. </li></ul><ul><li>- node positive primary. </li></ul><ul><li>- Local recurrence of primary </li></ul><ul><li>- Short disease free survival. </li></ul><ul><li>In most of the series extrahepatic disease is an exclusion criteria. </li></ul>
  • 85. Specific Features of Breast Metastases <ul><li>It is not uncommon for the background liver parenchyma to be scarred and fibrotic post chemotherapy. </li></ul><ul><li>Tumours may be harder to image/target. </li></ul><ul><li>More likely to get infiltrative lesions </li></ul><ul><li>This is reflected in positive resection margin rates post liver resection 35% (Adam 2006) </li></ul><ul><li>Development of multiple new tumours in a short-time frame. </li></ul>
  • 86. <ul><li>Some authors suggest that patients should first receive systemic chemotherapy and patients who do not progress only should be taken up for liver resection. </li></ul><ul><li>Valid criteria for patient selection cannot be defined at this time. </li></ul>
  • 87. Gastric and Pancreatic cancer <ul><li>Ochiai et al 1994, Br. J Surg 81:1175-1178. </li></ul><ul><li>6540 patients of gastric cancer, only 30 (0.46%) underwent resection for liver mets. </li></ul><ul><li>3 yr survival 20% and no 5 yr survivors. </li></ul>
  • 88. <ul><li>Pancreatic cancer: Detry et al, 2003 </li></ul><ul><li>No 3 yr survivors. </li></ul><ul><li>Liver resection cannot be recommended for these patients. </li></ul>
  • 89. <ul><li>10% of patients with renal tumors will develop Liver metastasis. </li></ul><ul><li>Less than 10% will survive for more than 1 yr. </li></ul><ul><li>Alves et al, 2003. Ann of Surg Onco 10:705-710. </li></ul><ul><li>Median survival was 26 months with 3 yr survival of 26%. </li></ul>
  • 90. <ul><li>DFI of less than 24 months and metastasis diameter of more than 5 cm were adverse prognostic factors. </li></ul><ul><li>Liver resection seems justified in patients where a complete resection is possible. </li></ul>
  • 91. Specific Features of Breast Metastases <ul><li>It is not uncommon for the background liver parenchyma to be scarred and fibrotic post chemotherapy. </li></ul><ul><li>Tumours may be harder to image/target. </li></ul><ul><li>More likely to get infiltrative lesions </li></ul><ul><li>This is reflected in positive resection margin rates post liver resection 35% (Adam 2006) </li></ul><ul><li>Development of multiple new tumours in a short-time frame. </li></ul>
  • 92. Germ cell tumors <ul><li>Gholam et al Cancer 2003. 98:745-752. </li></ul><ul><li>37 patients who had undergone liver resection for metastatic tumors. </li></ul><ul><li>All patients had developed Cisplatin based chemotherapy. </li></ul><ul><li>5 yr survival rate was 62%. </li></ul>
  • 93. <ul><li>Defined three adverse prognostic factors: </li></ul><ul><li>- Pure embryonal cell carcinoma in the primary tumor. </li></ul><ul><li>- Liver metastasis more than 3 cms. </li></ul><ul><li>- Presence of viable residual disease after chemotherpy. </li></ul>
  • 94. <ul><li>Male patients with liver tumors greater than 3 cms represented high risk group that may not benefit from liver resection. </li></ul>
  • 95. <ul><ul><li>Analysis of prognostic factors influencing long-term survival after hepatic resection for metastatic colorectal cancer. </li></ul></ul><ul><ul><li>Arru M , Aldrighetti L , Castoldi R , Di Palo S , Orsenigo E , Stella M , Pulitanò C , Gavazzi F , Ferla G , Di Carlo V , Staudacher C . </li></ul></ul><ul><ul><li>Department of Surgery, San Raffaele Scientific Institute, Via Olgettina 60, 20132, Milan, Italy. [email_address] World J Surg. 2008 Jan;32(1):93-103 </li></ul></ul><ul><ul><li>BACKGROUND: The aim of this study was to analyze the prognostic factors associated with long-term outcome after liver resection for colorectal metastases. The retrospective analysis included 297 liver resections for colorectal metastases. METHODS: The variables considered included disease stage, differentiation grade, site and nodal metastasis of the primary tumor, number and diameter of the lesions, time from primary cancer to metastasis, preoperative carcinoembryonic antigen (CEA) level, adjuvant chemotherapy, type of resection, intraoperative ultrasonography and portal clamping use, blood loss, transfusions, complications, hospitalization, surgical margins status, and a clinical risk score (MSKCC-CRS). RESULTS: The univariate analysis revealed a significant difference (p &lt; 0.05) in overall 5-year survival rates depending on the differentiation grade, preoperative CEA &gt;5 and &gt;200 ng/ml, diameter of the lesion &gt;5 cm, time from primary tumor to metastases &gt;12 months, MSKCC-CRS &gt;2. The multivariate analysis showed three independent negative prognostic factors: G3 or G4 grade, CEA &gt;5 ng/ml, and high MSKCC-CRS. CONCLUSIONS: No single prognostic factor proved to be associated with a sufficiently disappointing outcome to exclude patients from liver resection. However, in the presence of some prognostic factors (G3-G4 differentiation, preoperative CEA &gt;5 ng/ml, high MSKCC-CRS), enrollment of patients in trials exploring new adjuvant treatments is suggested to improve the outcome after surgery. </li></ul></ul>
  • 96. Analysis of prognostic factors influencing long-term survival after hepatic resection for metastatic colorectal cancer <ul><ul><li>The retrospective analysis n=297 liver resections for colorectal metastases. </li></ul></ul><ul><li>METHODS: The variables considered included </li></ul><ul><li>disease stage, differentiation grade, site and nodal metastasis of the primary tumor, </li></ul><ul><li>number and diameter of the lesions, time from primary cancer to metastasis, preoperative CEA level, adjuvant chemotherapy, type of resection, intraoperative ultrasonography and portal clamping use, blood loss, transfusions, complications, hospitalization, surgical margins status, and a clinical risk score (MSKCC-CRS). </li></ul>Arru M ,et al Italy, World J Surg. 2008
  • 97. Results of R0 Resection for Colorectal Liver Metastases Associated With Extrahepatic Disease Elias D et al ( France) Ann Surg Oncol 2004 <ul><li>After a median follow-up of 4.9 years (range, 1.7–13.4 years): </li></ul><ul><li>the 3- and 5-year overall survival rates were 45% and 28%, respectively among the patients with extrahepatic disease compared with 56% and 33%, for patients without EHD ( P = .15) </li></ul><ul><li>negative prognostic factors for surgery: </li></ul><ul><li>-presence of multiple EHD sites </li></ul><ul><li>- more than five liver metastases </li></ul>
  • 98. A Nomogram for Predicting Disease-specific Survival After Hepatic Resection for Metastatic Colorectal Cancer <ul><li>Posted 03/14/2008 </li></ul><ul><li>Michael W. Kattan, PhD; Mithat Gönen, PhD; William R. Jarnagin, MD, PhD; Ronald DeMatteo, MD; Michael D&apos;Angelica, MD; Martin Weiser, MD; Leslie H. Blumgart, MD; Yuman Fong, MD Author Information </li></ul><ul><li>Abstract and Introduction </li></ul><ul><li>Abstract </li></ul><ul><li>Purpose: To develop a tool for predicting survival after liver resection for patients with stage IV colorectal cancer. By using a nomogram we are trying to improve on the current practice of using prognostic scores for evaluating risks of therapeutic failure. Patients and Methods: All patients admitted to Memorial Sloan-Kettering Cancer Center (MSKCC) for curative intent for treatment of metastatic disease from colorectal cancer between January 1986 and December 1999 were included,( n=1477) . A nomogram was developed as a graphical representation of a Cox proportional hazards regression model. The nomogram was verified for discrimination and calibration, both employing bootstrapping to obtain relatively unbiased estimates. Results: Using nodal status of the primary tumor, disease-free interval, size of the largest metastatic tumor, preoperative carcinoembryonic antigen, bilateral resection, extensive resection (lobectomy or more), gender, number of hepatic tumors, primary cancer site (colon vs. rectum), and age, the nomogram achieved a concordance index of 0.61, statistically significantly greater than chance. The nomogram also had very good calibration. Conclusion: This nomogram is a predictive tool, upon external validation, that can routinely be used to counsel patients in making treatment decisions. The discriminatory ability of the nomogram indicates that this population should not be considered homogeneous with respect to risk of death. </li></ul>Ann Surg.  2008;247(2):282-287
  • 99. Tables for: A Nomogram for Predicting Disease-specific Survival After Hepatic Resection for Metastatic Colorectal Cancer [Ann Surg.  2008;247(2):282-287.
  • 100. Proposal of criteria to select candidates with colorectal liver metastases for hepatic resection: comparison of our scoring system to the positive number of risk factors. Nagashima I , Takada T , Adachi M , Nagawa H , Muto T , Okinaga K . <ul><ul><li>Department of Surgery, Teikyo University School of Medicine, 2-11-1, Kaga, Itabashi-ku, Tokyo 173-8605, Japan. inaga@med.teikyo-u ac.jp </li></ul></ul><ul><ul><li>AIM: To select accurately good candidates of hepatic resection for colorectal liver metastasis. METHODS: Thirteen clinicopathological features, which were recognized only before or during surgery, were selected retrospectively in 81 consecutive patients in one hospital (Group I). These features were entered into a multivariate analysis to determine independent and significant variables affecting long-term prognosis after hepatectomy. Using selected variables, we created a scoring formula to classify patients with colorectal liver metastases to select good candidates for hepatic resection. The usefulness of the new scoring system was examined in a series of 92 patients from another hospital (Group II), comparing the number of selected variables. RESULTS: Among 81 patients of Group I, multivariate analysis, i.e. Cox regression analysis, showed that multiple tumors, the largest tumor greater than 5 cm in diameter, and resectable extrahepatic metastases were significant and independent prognostic factors for poor survival after hepatectomy (P &lt; 0.05). In addition, these three factors: serosa invasion, local lymph node metastases of primary cancers, and post-operative disease free interval less than 1 year including synchronous hepatic metastasis, were not significant, however, they were selected by a stepwise method of Cox regression analysis (0.05 &lt; P &lt; 0.20). Using these six variables, we created a new scoring formula to classify patients with colorectal liver metastases. Finally, our new scoring system not only classified patients in Group I very well, but also that in Group II, according to long-term outcomes after hepatic resection. The positive number of these six variables also classified them well. CONCLUSION: Both, our new scoring system and the positive number of significant prognostic factors are useful to classify patients with colorectal liver metastases in the preoperative selection of good candidates for hepatic resection. </li></ul></ul>World J Gastroenterol. 2006
  • 101. Management of the hepatic lymph nodes during resection of liver metastases from colorectal cancer: a systematic review Gurusamy KS , Imber C , Davidson BR . <ul><li>University Department of Surgery, UCL and Royal Free Hospital NHS Trust, Royal Free and University College School of Medicine, London NW3 2QG, UK. kurinchi2k@hotmail.com </li></ul><ul><li>BACKGROUND: Hepatic lymph node involvement is generally considered a contraindication for liver resection performed for colorectal liver metastases. However, some advocate hepatic lymphadenectomy in the presence of macroscopic involvement and others routine lymphadenectomy. The aim of this review is to assess the role of lymphadenectomy in resection of liver metastases from colorectal cancer. METHODS: Medline, Embase and Central databases were searched using a formal search strategy. Trials with survival data with a minimum follow-up of 1 year were considered for inclusion. Meta-analysis was performed using Revman. RESULTS: A total of 4230 references were identified. Ten reports of nine studies including 926 patients qualified for the review. The prevalence of nodal metastases after routine lymphadenectomy was 16.3%. The overall 3-year and 5-year survival rates in node-positive patients were 9/151 (11.3%) and 2/137 (1.5%), respectively, compared to 3-year and 5-year survival rates of 424/787 (53.9%) and 246/767 (32.1%) in node-negative patients. The odds ratios for 3-year and 5-year survivals in node positive disease compared to node-negative disease were 0.12 (95% CI 0.06 to 0.24) and 0.08 (95% CI 0.03 to 0.22). There was no randomized controlled trial which assessed the survival benefit of routine or &amp;quot;selective&amp;quot; lymphadenectomy. CONCLUSION: Currently, there is no evidence of survival benefit for routine or selective lymphadenectomy. Survival rates are low in patients with positive lymph nodes draining the liver irrespective of whether they are detected by routine lymphadenectomy or by macroscopic involvement. Further trials in this patient group are required. </li></ul>HPB Surg. 2008;2008:684150
  • 102. Management of the hepatic lymph nodes during resection of liver metastases from colorectal cancer: a systematic review Gurusamy KS , Imber C , Davidson BR . <ul><li>BACKGROUND: Hepatic lymph node involvement is generally considered a contraindication for liver resection performed for colorectal liver metastases. </li></ul><ul><li>The aim of this review is to assess the role of lymphadenectomy in resection of liver metastases from colorectal cancer. </li></ul><ul><li>METHODS: Medline, Embase and Central databases were searched using a formal search strategy. Trials with survival data with a minimum follow-up of 1 year were considered for inclusion. Meta-analysis was performed using Revman. </li></ul><ul><li>RESULTS: A total of 4230 references were identified. Ten reports of nine studies including 926 patients qualified for the review. </li></ul><ul><li>The prevalence of nodal metastases after routine lymphadenectomy was 16.3%. </li></ul><ul><li>The overall 3-year and 5-year survival rates in node-positive patients were 9/151 (11.3%) and 2/137 (1.5%), respectively, </li></ul><ul><li>compared to 3-year and 5-year survival rates of 424/787 (53.9%) and 246/767 (32.1%) in node-negative patients. </li></ul><ul><li>CONCLUSION: Currently, there is no evidence of survival benefit for routine or selective lymphadenectomy. Survival rates are low in patients with positive lymph nodes draining the liver irrespective of whether they are detected by routine lymphadenectomy or by macroscopic involvement. Further trials in this patient group are required. </li></ul>HPB Surg. 2008;2008:684150
  • 103. Management of Liver Metastasis: Patient Selection <ul><li>resection of liver metastases, when possible, remains the preferred therapy for potential cure </li></ul><ul><li>The overall 5-year survival rates are in the range of 35%–58% in the major series reporting on the results of hepatectomy with curative intent </li></ul><ul><li>Patients with untreated metastatic colorectal cancer have a short median survival time of approximately 12 months </li></ul><ul><li>Although the progress of developing effective agents has accelerated, the median survival time of unresected patients is still in the range of 16–24 months, and survival beyond 5 years is uncommon </li></ul><ul><li>Ablative therapies are frequently used </li></ul><ul><li>Given that surgical resection remains the best chance for cure, </li></ul><ul><li>there has been considerable interest in expanding the criteria for resectability of patients with colorectal metastasis using other adjunctive and adjuvant approaches. </li></ul>
  • 104. Management of Liver Metastasis: Patient Selection in CRC Liver Metastases <ul><li>Neoajuvant Chemotherapy </li></ul>
  • 105. Recurrence and outcomes following hepatic resection, radiofrequency ablation, and combined resection/ablation for colorectal liver metastases. Abdalla EK , et.al. HoustonAnn Surg. 2004 <ul><li>Department of Surgical Oncology, University of Texas M. D. Anderson Cancer Center,, TX, USA. OBJECTIVE: To examine recurrence and survival rates for patients treated with hepatic resection only, radiofrequency ablation (RFA) plus resection or RFA only for colorectal liver metastases. SUMMARY BACKGROUND DATA: Thermal destruction techniques, particularly RFA, have been rapidly accepted into surgical practice in the last 5 years. Long-term survival data following treatment of colorectal liver metastasis using RFA with or without hepatic resection are lacking. METHODS: Data from 358 consecutive patients with colorectal liver metastases treated for cure with hepatic resection +/- RFA and 70 patients found at laparotomy to have liver-only disease but not to be candidates for potentially curative treatment were compared (1992-2002). RESULTS: Of 418 patients treated, 190 (45%) underwent resection only, 101 RFA + resection (24%), 57 RFA only (14%), and 70 laparotomy with biopsy only or arterial infusion pump placement (&amp;quot;chemotherapy only,&amp;quot; 17%). RFA was used in operative candidates who could not undergo complete resection of disease. Overall recurrence was most common after RFA (84% vs. 64% RFA + resection vs. 52% resection only, P &lt; 0.001). Liver-only recurrence after RFA was fourfold the rate after resection (44% vs. 11% of patients, P &lt; 0.001), and true local recurrence was most common after RFA (9% of patients vs. 5% RFA + resection vs. 2% resection only, P = 0.02). Overall survival rate was highest after resection (58% at 5 years); 4-year survival after resection, RFA + resection and RFA only were 65%, 36%, and 22%, respectively (P &lt; 0.0001). Survival for &amp;quot;unresectable&amp;quot; patients treated with RFA + resection or RFA only was greater than chemotherapy only (P = 0.0017). CONCLUSIONS: Hepatic resection is the treatment of choice for colorectal liver metastases. RFA alone or in combination with resection for unresectable patients does not provide survival comparable to resection, and provides survival only slightly superior to nonsurgical treatment. </li></ul>
  • 106. Neuroendocrine hepatic metastases: does aggressive management improve survival Touzios JG , Kiely JM , Pitt SC , Rilling WS , Quebbeman EJ , Wilson SD , Pitt HA . Wisconsin Ann Surg. 2005 <ul><li>OBJECTIVE: The aim of this study was to determine whether aggressive management of neuroendocrine hepatic metastases improves survival. SUMMARY BACKGROUND DATA: Survival in patients with carcinoid and pancreatic neuroendocrine tumors is significantly better than adenocarcinomas arising from the same organs. However, survival and quality of life are diminished in patients with neuroendocrine hepatic metastases. In recent years, aggressive treatment of hepatic neuroendocrine tumors has been shown to relieve symptoms. Minimal data are available, however, to document improved survival with this approach. METHODS: The records of patients with carcinoid (n = 84) and pancreatic neuroendocrine tumors (n = 69) managed at our institution from January 1990 through July 2004 were reviewed. Eighty-four patients had malignant tumors, and hepatic metastases were present in 60 of these patients. Of these 60 patients, 23 received no aggressive treatment of their liver metastases, 19 were treated with hepatic resection and/or ablation, and 18 were managed with transarterial chemoembolization (TACE) frequently (n = 11) in addition to resection and/or ablation. These groups did not differ with respect to age, gender, tumor type, or extent of liver involvement. RESULTS: Median and 5-year survival were 20 months and 25% for the Nonaggressive group, &gt;96 months and 72% for the Resection/Ablation group, and 50 months and 50% for the TACE group. The survival for the Resection/Ablation and the TACE groups was significantly better (P &lt; 0.05) when compared with the Nonaggressive group. Patients with more than 50% liver involvement had a poor outcome (P &lt; 0.001). CONCLUSIONS: These data suggest that aggressive management of neuroendocrine hepatic metastases does improve survival, that chemoembolization increases the patient population eligible for this strategy, and that patients with more than 50% liver involvement may not benefit from an aggressive approach. </li></ul>
  • 107. Resection versus no intervention or other surgical interventions for colorectal cancer liver metastases. Al- Asfoor A , Fedorowicz Z , Lodge M . <ul><ul><li>BACKGROUND: About one in four of patients with metastatic colorectal cancer have metastases isolated to the liver, of which 10% to 25% are eligible for ablation of the liver metastases, improving the five year survival rate.Treatments include hepatic resection and other modalities using cryosurgery and radiofrequency thermal ablation. Although new modalities allow safe ablation of liver metastases without the need for surgical intervention, there are still no clear guidelines on the appropriate management of patients with colorectal cancer and hepatic metastases. OBJECTIVES: The primary objectives were to compare resection of liver metastases to no intervention and other modalities of intervention (including cryosurgery and radiofrequency ablation) in terms of the benefits and harms for each intervention. SEARCH STRATEGY: Searches were conducted of the Cochrane Central Register of Controlled Trials, MEDLINE and EMBASE databases up to October 2006. In addition, references were scrutinized in identified eligible trials. SELECTION CRITERIA: Only randomized controlled trials reporting patients (regardless of age and sex) who had had curative surgery for adenocarcinoma of the colon or rectum, had been diagnosed with liver metastases and who were eligible for liver resection (i.e. with no evidence of primary or metastatic cancer elsewhere) were considered. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data using a form designed for this review. Discrepancies were resolved by consensus. MAIN RESULTS: Only one trial involving 123 people (87 male 36 female) was included. The data from this ten year prospective, randomized clinical trial suggest that hepatic cryosurgery is effective in the treatment of resectable and nonresectable liver metastases. The results show intra-operative tumor reduction (&gt;/=90% or &lt;/= 97%) and extended higher survival in these patients. The study indicated a five year and ten year survival rate of 44% and 19% after cryosurgery, respectively. However, it was not possible to separate out and unravel the outcomes data that related only to the participants (66.6%) with liver metastases from colorectal cancer as opposed to those with liver metastases from other primary tumors. AUTHORS&apos; CONCLUSIONS: There is currently insufficient evidence to support a single approach, either surgical or non-surgical, for the management of colorectal liver metastases. Therefore, treatment decisions should continue to be based on individual circumstances and clinician&apos;s experience. The authors conclude that local ablative therapies are probably useful, but that they need to be further evaluated in a randomized controlled trial. </li></ul></ul>Cochrane Database Syst Rev. 2008 Apr
  • 108. Analysis of prognostic factors influencing long-term survival after hepatic resection for metastatic colorectal cancer Arru M ,et al Italy, World J Surg. 2008 <ul><li>The retrospective analysis n=297 liver resections for colorectal metastases </li></ul><ul><li>The univariate analysis revealed a statistically significant difference (p &lt; 0.05) in overall survival in relation to : </li></ul><ul><li>grade of differentiation of the primary cancer (5-year survival of grades G1-G2 vs grades G3-G4: 30.7% vs 14.4%, p = 0.0016), </li></ul><ul><li>preoperative CEA level &gt; 5 and &gt; 200 ng/ml (5-year survival of CEA &lt; 5 ng/ml vs CEA &gt; 5 ng/ml: 51.1% vs 15.5%, p = 0.0016; </li></ul><ul><li>5-year survival of CEA &lt; 200 ng/ml vs CEA &gt; 200 ng/ml: 27.9% vs 17.4%, p = 0.0001), </li></ul><ul><li>diameter of major lesions &gt; 5 cm (5-year survival of diameter &lt; or = 5 cm vs &gt; 5 cm: 30.0% vs 18.8%, p = 0.0074), </li></ul><ul><li>disease-free interval between primary tumour and liver metastases longer than 12 months (5-year survival of patients with disease-free interval &lt; or = 12 months vs &gt; 12 months: 23.0% vs 36.1%, p = 0.042), </li></ul><ul><li>high MSKCC-CRS (5-year survival of MKSCC-CRS 0-1-2 vs 3-4-5: 36.4% vs 1 6.3%, p = 0.017). </li></ul>
  • 109. Management of Liver Metastasis: Patient Selection <ul><li>General criteria for fitness </li></ul><ul><li>Specific Criteria that decides the outcome in terms of: </li></ul><ul><li>- Risk of recurrence </li></ul><ul><li>- Survivals: Disease free and overall </li></ul><ul><li>Predictive factors for outcome of a therapy </li></ul>

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