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1、结直肠癌肝转移新辅助结直肠癌肝转移新辅助化疗的共识与争议化疗的共识与争议Epidemiology of colorectal cancer(CRC)Results of Hepatic Resection for Metastatic Colorectal CancerLiver metastases of CRCManagement of MCRC:An Evolving Treatment Algorithm Neoadj:where is the most controversyConcept of resectability手术的关注重点由手术的关注重点由“哪些可以切除哪些可以切除”转
2、变为转变为“哪些可以保留哪些可以保留”Timothy M.Pawlik 2008只要能够完全切除，转移灶的个数与长期生存率无关只要能够完全切除，转移灶的个数与长期生存率无关Altendorf-Hofmann A,Scheele J.A critical review of the major indicators of prognosis after resection of hepatic metastases from colorectal carcinoma.Surg Oncol Clin N Am 2003;12:165192 No.of met and resectability(A
3、):(A):不完全性切除患者的不完全性切除患者的MSTMST只有只有 14 14 月，而完全切除患者的月，而完全切除患者的MSTMST为为44 44 月。月。Altendorf-Hofmann A,et al.Surg Oncol Clin N Am 2003;12:165192.(B):只要能够完全切除，切除边界只要能够完全切除，切除边界的宽度对生存时间无明显影响。的宽度对生存时间无明显影响。Pawlik TM,et al.Effect of surgical margin status on survival and site of recurrence after hepatic res
4、ection for colorectal metastases.Ann Surg 2005;241:715722;discussion 722724Margin and resectability Neoadjuvant chemotherapy for resectable liver metastases of CRC resectablePreoperative chemotherapywhat are possible benefits?Tumor shrinkage may facilite resection whith a hope for higher survival ra
5、tes Test chemoresponsiveness of matastases Select candidates for resection -Exclude tumors progressing while on chemotherapy -Be more aggressive on responding tumorsEORTC 40983:Peri-operative chemotherapySize of lesions after pre-op chemotherapyPhase 3 Trial of Perioperative FOLFOX4 and Surgery for
6、Resectable CRC Liver Metastases(EORTC 40983):PFSRationale AGAINST neoadjuvant CT Risk that metastases become unresectable if they progress during chemotherapy Uncertainty about how to deal with“complete response”to chemotherapy Liver damage induced by chemotherapyPreoperative chemotherapy:potential
7、problems Lost window of opportunity Tumor growth in a critical area may render metastases unresectable Chemotherapy induced portal vein thrombosis 1.Donadon M,et al.W J Gastroenteral 12:6556,2006Survival according to response to neoadjuvant chemotherapy ATE：cerebral infact,myocardial infarction,TIA,
8、angina Risk factors for developing ATE Age 65 y(P=0.01)Prior history of ATE(P 4.5 cm Residual tumor identified:83%Chemotherapy reduces sensitivity of PET detection of matastases2,31.Benoist S,et al,J Clin Oncol 24:3939,20062.Akhurst T,et al,J Clin Oncol 23:8713,20053.Tan,MCB et al,J Gastrointest Sur
9、g 11:1112,2007“Complete response”:does it cure?Complete responsePreoperative chemotherapy:potential problemsRadiographic CR Pathologoc CR Radiographic CR Pathologoc CR1 Resection strategy must remove these lesions“Blind”removal sounds easy in conceptBenoist S,et al,JCO 24:3939,2006Chemotherapy induc
10、es liver damage The“blue”liverThe type of liver injury depends on drug administered Vascular lesions:Oxaliplatin (Rubbia-Brandt et al,2004)Steatosis:5FU,Irinotecan?(Parikh et al,2003)Steatohepatitis:Irinotecan (Vauthey et al,2006)Liver damage induced by chemotherapySinusoidal lesionsSteatohepatitisA
11、SCO AMERICAN SOCIETY OF CLINICAL ONCOLOGYVascular Change in Liver Post Systemic Chemotherapy Clinical significance:impact on surgery Clinical outcome related to liver damage Steatosis associated with higher infection rate Steatosis associated with higher infection rate (Kooby et al,2003)(Kooby et al
12、,2003)Steatohepatitis associated with higher mortality rate due Steatohepatitis associated with higher mortality rate due to liver failure after surgery to liver failure after surgery (Vauthey et al.2006)(Vauthey et al.2006)Vascular injury associated with higher rate of operative Vascular injury ass
13、ociated with higher rate of operative bleeding and transfusion requirementbleeding and transfusion requirement (Vauthey et al.2006.Aloia et al.2006)(Vauthey et al.2006.Aloia et al.2006)Peroperative chemotherapy:potential problemsEORTC 40983:impact of pre-operative chemotherapy on surgeryB O S(Biolog
14、ics,Oxaliplatin,Surgery)EORTC 40051Resectable CRC liver metastases:Unanswered Questions Is peri-operative chemotherapy superior to post-operative chemotherapy?How much preoperative chemotherapy?How do you assess nature and extent of chemotherapy-induced liver injury?Do targeted agents modulate chemo
15、therapy-induced liver injury?Neoadj for unresectable liver metastases of CRC Chemotherapy for unresectable Is there a benefit to add surgery to chemotherapy?To which patients?With what regimens?After how much duration of treatment?Take-home message Chemotherapy for unresectable Is there a benefit to
16、 add surgery to chemotherapy?To which patients?With what regimens?After how much duration of treatment?Take-home messageDownstaging UnresectableColorectal MetastasesResponse to neoadjuvant chemothrapySurvival after liver Resection of Non Resectable Colorectal Matastases after Systemic Chemotherapy Survival after liver Resection of Colorectal MatastasesSurvival After Chemotherapy For CRLMEffective Preoperative Therapy+Hepatic Resection:Long-term Results in“unresectable”Patients Chemotherapy for u
