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  1. 1. Treatment of hepatic metastases in colorectal cancer French consensus conference 2003
  2. 2. Colorectal cancer A major health concern 1 million new cases/year worldwide 10 to 15% of all cancers Higher incidence in Western countries 1 in 20 people will be affected Mortality A leading cause of cancer death (with lung and breast cancers) ~ 50% of CRC patients will die from their disease <ul><li>JF. Fraumeni et al., Principles and Practice in Oncology, 1993 </li></ul><ul><li>D. Cunningham, M. Findlay, Eur. J. Cancer, 1993; 29A, 15: 2077-79 </li></ul>
  3. 3. Liver metastases from colorectal cancer 1. Kemeny et al (1999); 2. Seifert (1998); 3. Borner ( 1999) Liver, the most common site of metastases from CRC – 50 to 75% of patients with advanced CRC will develop liver metastases 1 – 15 to 25% of patients of any stage have liver metastases at presentation 1, 2 – 20 to 35% of patients with metastatic disease confined to the liver 3 Surgery of liver metastases is at a turning point
  4. 4. <ul><li>Per operative ultrasound should be done in surgery of colon cancer </li></ul>
  5. 5. Arguments for hepatic metastases resection <ul><li>Without resection, survival up to 5 years : rare (1) </li></ul><ul><li>Resected : 5 years 30-40%, 10 years 25% </li></ul><ul><li>Low operative mortality 0-6% </li></ul><ul><li>Chemotherapy only: 3 years <20% </li></ul><ul><li>Resection must be RO : </li></ul><ul><li>Results of resection non RO is equivalent to absence of treatment (2) </li></ul><ul><li>Wagner Ann Surg 1984,Hugues Surg Clin North Am 1989,Wood Clin Oncol 1976 </li></ul><ul><li>2. AFC 1996, Hughes K. Surg Clin North Am 1989, Bakalakos EA. World J Surg 1998, Ohisson B. World J Surg 1998 </li></ul>
  6. 6. Surgery of liver metastases: potential for long-term survival <ul><li>SM. Wilson, MA. Adson, Arch. Surg., 1976; 111: 330-34 </li></ul>25% 60 non operated patients 60 operated patients Survival (in months) 120 CRC patients with comparable N. of liver metastases and extent of disease 10 20 30 40 50 60 70 80 90 100 % of patients 10 20 30 40 50 60 70 80 5 years
  7. 7. Questions <ul><li>1 What investigations ? </li></ul><ul><li>2 What metastases are immediately resectable ? </li></ul><ul><li>3 What is the place of the chemotherapy ? </li></ul><ul><li>4 What are conditions and possibilities of treatment by local ablation ? </li></ul><ul><li>5 What is possible to make metastases resectable ? </li></ul>
  8. 8. Evidence base levels Grade A : scientific diagnosis established : (gradeA) Level 1 of scientific evidence Trial and meta-analyses and comparative randomised studies Analyses conducted on well organised studies Grade B : scientific diagnosis presumption: (grade B) Level 2 cohort studies, low level randomised comparative trials , non randomised controlled clinical trial well performed Grade C, low scientific diagnosis level : (grade C) Level 3 Case report, control-tests Level 4 Retrospective and comparative studies with important bias, case series, developped studies of epidemiology ….. consensus
  9. 9. 1 What investigations ? Complete physical examination ( OMS 3> Stop) Colonoscopy CEA useful after therapeutic response ( grade C) Ultrasound: Limits T< 1cm differentiate metastases (MRI) from other benign tumors CT with contrast > ultrasound ( gradeB ) MRI with liver contrast agents = CT scan ( grade B) MRI + gadolinium if doubt on CT or if CT not possible ( grade B) 1.McCall JL Dis Colon Rectum 1994 - 2. Renehan AG méta-analyse BM J2002
  10. 10. It is mandatory to look for a local reccurence and extra hepatic metastases
  11. 11. local recurrence and extra hepatic metastases <ul><li>Clinical evaluation </li></ul><ul><li>colonoscopy … if extra luminal : difficult </li></ul><ul><li>endosonography </li></ul><ul><li>MRI > pelvic CT scan++(1) PET ? (2) </li></ul><ul><li>Pulmonary metastases Chest CT ( grade B) </li></ul><ul><li>Abdominal lymph nodes PET promising (4) </li></ul><ul><li>Peritoneal disease PET scan ? variations within the results (4,5) </li></ul><ul><li>M any false positives and negatives Laparoscopy if doubt about irresectability </li></ul><ul><li>1.Kinkel K radiology 1996, Krestin GP radiology 1988 - 2.Flamen P J Clin Oncol 1999, Takeuchi O Br J Surg 1999)– 4. Lai DT. Arch Surg 1996 – 5. Huntinx R. Gastroenterol Clin Biol 1999 </li></ul>
  12. 12. PETscan (FDG) within evaluation patients with high risks of dissemination (grade B) métastases Se 88-90% Sp 95> (méta-Analyses: Huebner RH J Nucl Med 2000 Kinkel K Radiology 2002)
  13. 13. 2 What metastases are immediately resectable ?
  14. 14. Resection for CRC liver metastases: the traditionally perceived criteria Metachronous detection Unilobar disease < 4 metastases > 1 cm resection margin If we accept these criteria, then very few patients are eligible for surgery
  15. 15. <ul><li>1.Technical criteria </li></ul><ul><li>(volume of hepatic tumor) </li></ul>2. Carcinological criteria Criteria of resection
  16. 16. 1.Technical criteria : per-operative Visual and manual exploration ( grade C) Per-operative ultrasonography ( grade C) Modify therapeutic data in 10 to 42% of cases(1) More efficient than porto-scan and helical (2) Can be done by laparoscopy (3) Avoid useless laparotomy Technical efficiency but less reliable for node evaluation and posterior liver segments exploration (consensus) 1 Castaing 1986, Boutkan 1992, Machi 1993, Kane 1995 2 TDMBloed W 2000, Schmidt J 2000, Jamagin WR 2001 - 3 Milsom JW 2000, Jarnagin WR 2000
  17. 17. Resectable yes but? Reserve of hepatic tissue adequate (hepatic insufficiency) ? functional (vascularization and biliary drainage ) ? Anticipated mortality and minimal morbidity? Global morbidity 8-23% (1) Global mortality 1-2% (2) 1 Aaron R. Seminar in oncology 2002 – 2 Belghiti J. Am Coll Surg 2000)
  18. 18. Anatomic possibility of resection : Solitary or multiple unilobular tumors Irresectability : rare Size: no problem Location (caudate lobe) (1) Vascular limits : Involving the portal confluence : rare, no posterior approach Involving inferior veina cava : Hepatic vascular exclusion (TVE) With (2) or without preservation of caval flow ( 3) Replacement (4) of veina cava Vascular reconstruction(5) of hepatic vein Ex-situ in- vivo liver surgery (6) 1 Launois B. Ann Chirg 1990, Tono T Int Surg 2000 - 2 Cherqui D Ann Surg 1999 - Torzilli G Ann Surg 2001 - 3 Edmond JC 1996, Evans PM 1998, Huguet C 1992 - 4 Torzilli G Ann Surg 2001, Miyasaki M Am J Surg 1999 - 5 Nakamura S 1997 - 6 Hannoun L lancet 1991
  19. 19. Anatomic possibility of resection Bilateral multiple tumors Several segmentectomies with respected vascularisation of remnant liver Limitation: Number and areas of metastases More than 6 segments involved or 5 separated Vascular connections : involving 2 portal pedicles Liver transplantation not advisable (ANAES 1993)
  20. 20. Is hepatic resection safe ? Risk evaluation Hepatocellular insufficiency : 1- 5% of major hepatectomies Depend on remnant hepatic parenchyma and its pre and post-operative condition Remnant hepatic mass : prediction scoring system : liver volume by CT Okhamato (1984) or URATA (1995) Hepatology Resection limits : HCI risk for a healthy liver when >40% no risk remnant 25-40% increased liver <25% hepatectomy contra-indicated (C,4)
  21. 21. Three-dimensional reconstructions for anatomic liver resection with CT or MRI <ul><li>Aim: </li></ul><ul><li>Location of T. according to vessels (1) </li></ul><ul><li>Size of remnant liver (virtual residual hepatic volume ..) (2) </li></ul><ul><li>The anticipated evaluation of the remnant liver is requested if large resection ( grade C) </li></ul><ul><li>Its depends upon : </li></ul><ul><li> quantitative volume 25 to 40% ( grade C) </li></ul><ul><li> qualitative liver parenchyma </li></ul><ul><li>1 Lamade W Ach Surg 2000 Wigmore SJ Ann Surg 2001 </li></ul>
  22. 22. To summarize : Anatomic possibility of resection Simple resectability : classic hepatectomy leaving 40%> of liver parenchyma (resectability class I ) : (I*) Possible resectability : hepatectomy difficult or very large requesting a risky and/or a difficult procedure (resectability class II) : ( II*)
  23. 23. <ul><li>2. Carcinological criteria </li></ul><ul><li>possibility of resection </li></ul><ul><li>1° Initial pathology </li></ul><ul><li>2° Hepatic disease </li></ul><ul><li>3° Surgical technique </li></ul><ul><li>4° Extra hepatic disease 5° Metastatic disease </li></ul>
  24. 24. Initial pathology : Synchronic metastases No increase risk for combined resection (1) Pro: Non randomized series (2) and comparative series (3) Con: Sequential resection does increase the survival : 5 years survival: 35%/13%)(3) Allows appropriate selection of the patients. Recommendation: Combined resection is possible except for complex resection, advanced disease or emergency case (consensus) 1. Elias D. Am J Surg 1995, Jaeck D. Ann Chir 1996 – 2. Scheele J. Chirurg 2001, Lyass S. J Surg Oncol 2001. – 3. Vogt P. World J Surg 1991 – 3 Jenkins LT. Am Surg 1997, Lambert LA. Arch Surg 2000
  25. 25. Initial pathology : Metachronic metastases Advanced stage of colon cancer is not a contra-indication to resection (1) Quality of colon surgery has his own prognosis (2) Local recurrenc is not a contra-indication if resected at the same time (3) Recommendation: The tumor stage should not change the indication 1.Jamison RL Arch Surg 1997, Doci R Tumori 1995 - 2. Wigmore SJ. Ann Surg 1999 3. Scheele J. surgery 1991
  26. 26. Hepatic disease : Morphological features of metastases <ul><li>Not a contra-indication to resection: </li></ul><ul><li>Size: Poor prognosis if >5-10cm (1) </li></ul><ul><li>Number: poor prognosis if N>3-4. </li></ul><ul><li> 5 year survival 24% (1) , 10 years : 20% (2) </li></ul><ul><li>Bilobular localization : is not a prognostic factor. </li></ul><ul><li>Size, number and bilobular localization combined </li></ul><ul><li> % involved liver </li></ul><ul><ul><li>Is a prognostic factor if >20% (3), 25-50% (4), 30% (5), 50%(6) </li></ul></ul><ul><li>1. Fong Y.Ann Surg 1999 - 2. Minagawa M. Ann Surg 2000 – 3 Elias D. Ann Chir 1999 - 4 Doci R. Tumori 1995 – 5 Lise M.World J Surg 2001 – 6 Rosen SA. Arch Surg 2000 </li></ul>
  27. 27. Hepatic disease : Relapses after liver resection 1 - R. Adam et al., Ann. Surg., 1997 - 2 - B. Nordlinger et al., Cancer, 1996 - 3 - HJ. Wanebo, et al., Surgery, 1996 Tumor relapse will occur in 60-70% of resected patients (1, 2) Recurrences are confined to the liver in 20-30% of cases (3) Iterative resection is possible in 10-25% of patients (1, 3) Long-term results after iterative resection are comparable to those obtained after a first hepatectomy (1) The relevance of rehepatectomy is based on the arguments listed to the initial hepatectomy ( grade C )
  28. 28. Results of iterative resections Author, year N. of Operative 5-yr patient mortality survival rate Nordlinger, 1994 (1) 130 0.9% - Fernandez Trigo, 1995 (2) 170 - 32% Pinson, 1996 (3) 134 1.9% 40% Adam, 1997 (4) 64 0% 41% 1 - B. Nordlinger et al., JCO 1994 3 - CW. Pinson et al., Ann. Surg., 1996 2 - V. Fernandez Trigo et al., Surgery 1995 4 - R. Adam et al., Ann. Surg., 1997
  29. 29. Oncological resection possibility Recommendation If easy (class I : I*), resection must be done (whatever number, size, vascular or biliary invasion, ECA level) (grade C) If possible but risky (class II : II*), relevance of neo-adjuvant chemotherapy (clinical trial) (consensus)
  30. 30. Carcinological resection possibility Related factors to surgical technique Security margin resection: 1 cm-5 mn, (consensus) 2mn (1) Margin non independent prognosis factor (2) Importance of Ro. surgery (3) Type of exeresis : anatomical or nonanatomical resection: no recommendation If possible: liver sparing approach (4) so to enable repeated resection of the liver. importance of resection margin ++ 1 Makuuchi Arch Surg 2002 - 2 Elias D. J Surg Oncol 1998 – 3 Weber SM Ann Surg Oncol 2000, Scheele J Chirurg 2001 – 4 Kokudo N.am J Surg 2001
  31. 31. Related factors to extra hepatic disease Lymph node involvement : Hepatic pedicle involvement Rare 1-12.5% microscopic 11-19% (1) 5 years survival = 0(2), 3.4% (3) even if microscopic involvement (4). French register : 5 years 12% Regional lymph nodes ? If microscopic involvement = chemotherapy ? Pre-operative coeliac lymph node involvement : no exeresis Per-op: I* : exeresis can be considered. but within multidisciplinary decision ( grade C) II* : no exeresis ( grade C) 1 Elias D. Br J Surg 1996. Gibbs JF Cancer 1998. Ekberg H. Br J Surg 1986 – 2 Ekberg H. Br J Surg 1986 3 Rodgers MS Br J Surg 2000 - 4 Beckurts KT Br J Surg 1997 .
  32. 32. Related factors to extra hepatic disease : Other intra-abdominal localizations If resectable : yes 21% to 5 years. (1) 18% (2) But increased risk if operation combined If two surgical procedures : treat the liver first If high risk of resection (II*) or factors of poor prognosis : chemotherapy 1° If non resectable : surgical contra-indication (consensus) 1 Makuuchi Ann Surg 2000 - 2 Blumgart LH. Ann Surg 1999
  33. 33. Related factors to extra hepatic disease : Other intra-abdominal localizations Peritoneal disease 3.3% (1) : no resection laparoscopy if suspicion and/or large laparotomy (2) On trials : cyto reductive surgery followed by immediate intraperitoneal chemotherapy: 3 years survival : 40% (3) 1 Jarnagin WR. Am Coll Surg 1999 - 2 Gibbs JF. Cancer 1998 - 3 Elias D. J Surg Invest 2001, Sugarbaker PH. Ann Ital Chir 1996.
  34. 34. Related factors to extra hepatic disease : Extra-abdominal localizations Pulmonary metastases resected : 5 years survival rate of 28-52% (1,4) If resection, treat thtee liver first after brain CT scan (2) ( grade C) Other metastases : contra-indication (gradeC) 1 Murata S. Cancer 1998. Robinson BJ. J Thorac Cardiovasc Surg 1999. - 2 Wronski M. Cancer 1999 - 3 Nagakura S. J Am Coll Surg 2001 – 4 Headrick JR. An Thorac Surg 2001
  35. 35. 3 What is the place of chemotherapy ? 1 Adjuvant chemotherapy <ul><li>Hepatic arterial infusion (H.A.I.) </li></ul><ul><li>Intravenous (I.V.) </li></ul>
  36. 36. H.A.I. after RO resection H.A.I.C./ O randomised prospective (1) : 5Fu- Folinic Ac/control (n=226 ) therapeutic inefficiency and important toxicity . H.A.I.C. + I.V.C. / O randomised ECOG-SOG (2) : Fin favour of chemotherapy (M: 63.7 /49 mois) H.A.I.C. + I.V.C./ I.V.C. Memorial (3) :In favour of combined arm (M: 72.2/59.3 mois) . Prospective (4) : In favour of combined treatment H. A.I.C. ( FUDR)+ I.V.C. favorable ( grade B) but high cost and high morbidity, not available in Europe 1 Lorenz M Ann Surg 1998 - 2 Kemeny MM. J Clin Oncol 2002 - 3 Kemeny N Engl J Med 1999 4 Lygidakis Hepatogastroenterolgy 2001
  37. 37. I.V.C. after RO resection Retrospective studies: FFCD (Portier G. J Clin Oncol 2002) I.V.C. /control : N.S. Study inter-group europeo-canadian (Langer B. J Clin Oncol 2002) N.S. After Ro resection : Testing of new molecules : yes if no testing: no evidence of benefit (grade B,C) but the consensus suggest a sytemic association 5Fu-folinic ac
  38. 38. Intravenous chemotherapy after RO resection Resectable metastases after neoadjuvant chemotherapy. To continue chemotherapy according to : importance of response, cumulative toxicity, post-operative course (Consensus) After local ablation (RF, cryotherapy): no consensus multidisciplinary decision
  39. 39. <ul><li>Neoadjuvant </li></ul><ul><li>chemotherapy </li></ul>
  40. 40. Objectives of neoadjuvant chemotherapy <ul><li>Resectable metastases : Reduce the reccurence risk post resection and/or make the resection easier (no published trials) </li></ul><ul><li>Non resectable metastases : </li></ul><ul><li>Improve resectability </li></ul>
  41. 41. Consensus about neoadjuvant chemotherapy <ul><li>Classe I : </li></ul><ul><li>resectable and no poor prognosis criteria : </li></ul><ul><li>No neoadjuvant chemotherapy except on trial (consensus) </li></ul><ul><li>Classe II and/or poor prognosis criteria: </li></ul><ul><li>Possible neoadjuvant chemotherapy (trials) (consensus) </li></ul><ul><li>Synchrone metastase non initialy resected : </li></ul><ul><li>In-between chemotherapy (consensus) </li></ul>
  42. 42. <ul><li>Conditions and possibility </li></ul><ul><li>of treatments </li></ul><ul><li>by </li></ul><ul><li>local destruction. </li></ul>
  43. 43. Local ablation of hepatic metastases <ul><li>in addition to improve surgical treatment with multiple unresectable C.R. metastases </li></ul><ul><li>Subject to clinical trials </li></ul><ul><li>Radiofrequency </li></ul><ul><li>Cryothérapy </li></ul><ul><li>Laser hyperthermia </li></ul><ul><li>Microwave coagulation Therapy </li></ul>RF
  44. 44. Local ablation of hepatic metastases <ul><li>Various techniques </li></ul><ul><li>alcohol Injection inefficient ( consensus) </li></ul><ul><li>R.F. : if it is per cutaneous ( consensus) </li></ul><ul><li>Technique: </li></ul><ul><li>No ablation method is required except If sub capsular tumor : surgical approach ( consensus) </li></ul><ul><li>With guiding imaging (PA) and post-therapeutic modification around the tumor >1 cm (grade C) </li></ul><ul><li>Control: </li></ul><ul><li>CT or MRI with injection > ultrasonography (grade C) </li></ul><ul><li>Periodicity : every 2 or 3 months the 1° year (consensus) </li></ul>
  45. 45. Local ablation of hepatic metastases (consensus) Indications: T. <3cm R.F. or laser or cryotherapy but if 3 cm> cryotherapy (1) Nb < 4 In proximity of a vessel 4mn > temporary occlusion Contra-indications: Next to the biliary duct or 1 cm< hilar Patients with a biliodigestive anastomosis Risk of septic complications ++ Next to the digestive- tract if per-cutaneous 1. Bilchick AJ 2000
  46. 46. Radiofrequency Nb Pts  moyen Survival 3 y Per cutaneous : Solbiati 1999 120 3,1 cm 38 % Gillams 1999 69 3,9 cm 54 % Per operative : RF 14 2,7 14% Resection 16 3,4 23% NS (prospective, non randomized) Shibata et al. Cancer 2000; 89: 276-84
  47. 47. Cryotherapy - 196° . Respect of vessels
  48. 48. <ul><ul><li>Wallace JR. Surgery 1999 - Finlay IG. Eur J Surg 2000 </li></ul></ul>Prospective non randomized studies Survival 38% 37% Résection (33 pts) Résection + cryo (24 pts)
  49. 49. Indications of local ablation <ul><li>Nothing better than resection (consensus) </li></ul><ul><li>Treatments not approved </li></ul><ul><li>Multidisciplinary approach </li></ul><ul><li>Alone or per-operative, must totally eradicate the disease </li></ul><ul><li>Should be focused on non resectable metastases </li></ul><ul><li>This treatment should concern only operable patients within trial </li></ul>
  50. 50. <ul><li>How we can improve the resectability rate </li></ul><ul><li>for colorectal metastases initially </li></ul><ul><li>Non resectable </li></ul>
  51. 51. Nonresectable hepatic metastases <ul><li>Positive margin </li></ul><ul><li>Nonresectable Presence of unresectable </li></ul><ul><li>(consensus) intra or extrahepatic disease </li></ul><ul><li>Inability to preserve an adequate reserve of functional hepatic tissue (25-40%) </li></ul><ul><li>To enhance resectability, 3 points (consensus.) : </li></ul><ul><li>Downstaging intra and/or extrahepatic disease, aim : RO </li></ul><ul><li>Eradicate the numerous and diffused metastases aim : RO </li></ul><ul><li>Induce hypertrophy of the remnant liver to 25-40% </li></ul>
  52. 52. To enhance resectability <ul><li>Neoadjuvant chemotherapy </li></ul><ul><li>Local ablation </li></ul><ul><li>Portal vein embolization </li></ul><ul><li>Two stage hepatectomy  </li></ul>
  53. 53. Neoadjuvant chemotherapy <ul><li>Surgery remains the only potentially curative treatment in metastatic CRC (1) </li></ul><ul><li>Only 10-20% of patients presenting with metastatic disease are candidate for curative resection (2) </li></ul><ul><li>Systemic chemotherapy in advanced disease improves survival (3) and quality of life (4) but does not allow to obtain long-term survival (2) </li></ul><ul><li>Development of combined modality approach: preoperative chemotherapy to allow secondary resection in patients with initially unresectable CRC metastases (2) </li></ul><ul><li>1 - Bismuth H. et al., Ed. D. Cunningham et al., 1999 - 2 - Adam R. et al., Ann. Surg. Oncol., 2001 - 3 - Scheithauer W. et al., BMJ, 1993 - 4 - Glimelius B. et al., Cancer, 1994; 73, 3: 556-62 </li></ul>
  54. 54. Adam et al (2001) 300 250 200 150 100 50 0 95/701 (11%) 171 (20%) No. of pts Oxali/5-FU/LV increased the proportion of patients resected by 55% Initially resectable Initially non-resectable, resectable with oxaliplatin Ability of oxaliplatin-based chemotherapy to allow secondary surgery in metastatic CRC
  55. 55. Five-year survival following secondary surgery in metastatic CRC Survival time (years) 1.0 0 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 0 1 2 3 4 5 Proportion surviving 91% 50% 34% n=95 Survival of patients initially non-resectable, made resectable with oxali/5-FU/LV Adam et al (2001)
  56. 56. Survival according to categories of initial non resectability (n=95) Adam et al (2001) 18% Extrahepatic (26) Proportion surviving 1.0 0 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 0 1 2 3 4 5 Survival time (years) 34% Multinodular (48) 60% Large (9) 49% -located (12)
  57. 57. Survival after oxaliplatin-based chemotherapy and surgery 58 patients: macroscopically complete resection 74 non-operated patients 30% 50% Giacchetti et al (1999) Time (years) Patients (%) 100 0 80 60 40 20 0 1 2 3 4 5 6 7 8 9 77 operated patients 151 patients with initially unresectable liver metastases
  58. 58. Impact of oxaliplatin on resection of colorectal liver metastases: Liverpool experience July 2001 CEA 997 Jan 2002 CEA 3
  59. 59. Resection rates after FOLFOX in initially inoperable patients Patients 51% 32% 13.6% 35.7% 18.9% resected (%) Complete 38% 21% 13.6% 28.5% 11.7% resection 5-year 50% – 35% – – survival (%) Study Giachetti Giachetti Adam Alberts Tournigand
  60. 60. Neoadjuvant chemotherapy <ul><li>Neo-adjuvant therapy improves resectability rates (C) </li></ul><ul><li>Results similar to primary surgery (C) </li></ul><ul><li>5Fu- folinic Ac + irinotecan or oxaliplatin (C) </li></ul><ul><li>Morphological evaluation every 2-3 months (CT scan or MRI) </li></ul><ul><li>(consensus ) </li></ul><ul><li>If effective minimum time of treatment : 3 months (C) </li></ul><ul><li>Surgery 1 month after chemotherapy treatment (consensus) </li></ul><ul><li>Resect metastases before they disappear or resect all the initial areas (consensus) </li></ul><ul><li>After surgery : continuation of chemotherapy depending on treament’s duration and efficiency (consensus) </li></ul>
  61. 61. Local ablation <ul><li>Indications : </li></ul><ul><li>To reinforce surgery in case of multiple localizations and high number of métastases </li></ul><ul><li>Proximity of the tumor with a major vessel </li></ul><ul><li>Too enormous hepatic resection </li></ul><ul><li>Poor clinical condition not allowing surgery </li></ul><ul><li>Particularities: </li></ul><ul><li>In addition to resection R1 : cryotherapy </li></ul><ul><li>Preparation of an hemiliver during a colorectal surgery or before portal embolization (RF) (gradeC) </li></ul><ul><li>Theses techniques must be performed in specialized centers </li></ul><ul><li>and be subjected to larger clinical trials (consensus) </li></ul>
  62. 62. Portal vein embolization to Induce hypertrophy of the remnant liver
  63. 63. Portal vein embolization technique (PVE) <ul><li>Pre-operative or intra-operative PVE induces hypertrophy of the remnant liver and increases safety (1) </li></ul><ul><li>Substances : </li></ul><ul><li>Lipiodol, Gelfoam, coils, polyvinilique alcohol, absolute alcohol, Cyanoacrylate++ (2) </li></ul><ul><li>Cyanoacrylate : Hypertrophy is 90% after 30 days </li></ul><ul><li>Absolute alcool : importance of necrosis and periportal fibrosis. Major side effects ++ </li></ul><ul><li>PVE: no major side effect (1) </li></ul><ul><li>Must be atraumatic : percutaneous ++ (grade C) </li></ul><ul><li>Hepatectomy after 30-45 days (grade C) </li></ul><ul><li>1 Makuuchi M. Surgery 1990 - 2 De Baere T. Hepatology 1996 </li></ul>
  64. 64. Right portal vein embolization P.E. (D0) Hépatectomy (D50-60) (Small left lobe)
  65. 65. Portal vein embolization Indications : depends on the rate of remnant functional liver parenchyma (CT) < 25% : essential > 40% : not advisable 25-40% : treatment’prescriptions to be treated separately according to the duration of neoadjuvant chemotherapy, the possible ischemic operation time and the complexity of the resection surgery (grade C) Survival up to 5 years : 40% (Azoulay D. Ann Surg 2000) 37% (Elias D. Surgery 2002)
  66. 66. « Two stage hepatectomy » <ul><li>Based on the association of combined or sequential treatments : </li></ul><ul><li>Neoadjuvant chemotherapy </li></ul><ul><li>Local ablation </li></ul><ul><li>Portal vein embolization </li></ul><ul><li>Hepatic resection </li></ul>
  67. 67. Right portal vein embolization and two stage hepatectomy Right P.E. (D14) Right hepatectomy (D70-80) 1° step (D0) Résection of left liver metastases  3 nodules
  68. 68. « Two stage hepatectomy » <ul><li>Selected patients </li></ul><ul><li>Multidisciplinary approach </li></ul><ul><li>Technique in evaluation </li></ul><ul><li>Specialized centers (*) </li></ul><ul><li>* Adam R. Ann Surg 2000 </li></ul>
  69. 69. Conclusion <ul><li>Multidisciplinary approach </li></ul><ul><li>Multimodality approach of treatment </li></ul><ul><li>Participation to therapeutic trials </li></ul><ul><li>Metastases’treatments to be done in specialized centers </li></ul>

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