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结直肠癌肝转移患者在肝切除术前接受结直肠癌化疗不会对围手术期结局产生不利影响。

Chemotherapy for colorectal cancer prior to liver resection for colorectal cancer hepatic metastases does not adversely affect peri-operative outcomes.

作者信息

Sahajpal Ajay, Vollmer Charles M, Dixon Elijah, Chan Elisa K, Wei Alice, Cattral Mark S, Taylor Bryce R, Grant David R, Greig Paul D, Gallinger Steven

机构信息

University of Toronto, Toronto, Ontario, Canada.

出版信息

J Surg Oncol. 2007 Jan 1;95(1):22-7. doi: 10.1002/jso.20632.

Abstract

BACKGROUND

Systemic chemotherapy is being used increasingly in patients with colorectal cancer. The effects of prior systemic adjuvant or palliative chemotherapy on morbidity following hepatic resection for metastases are not well defined.

OBJECTIVES

To assess the peri-operative impact of systemic chemotherapy on liver resection for colorectal cancer hepatic metastases.

METHODS

Ninety-six resections for colorectal cancer hepatic metastases performed from July 2001 to July 2003 (93% > or =2 segments) were reviewed. Pre-operative demographics, peri-operative features, and post-operative outcomes were collected prospectively. Type of chemotherapy and the temporal relationship of chemotherapy to the liver resection were analyzed.

RESULTS

Fifty-three of 96 patients (55%) received a mean of 5.7 cycles (6.1 months) of systemic chemotherapy prior to hepatic resection, with a median interval of 12 months from end of chemotherapy to liver resection (range 1-75 months). Thirty-five received 5-fluorouracil/leucovorin (5-FU/LV) alone, nine had irinotecan (CPT-11) in addition to 5-FU/LV, and nine were not specified. Pre-operative age, sex, co-morbidities, ASA score, biochemical and liver enzyme profiles, tumor number, and extent and technique of hepatic resection were the same in the chemotherapy and non-chemotherapy cohorts. Mean tumor size was smaller (4.5 cm vs. 5.8 cm) and synchronous metastases were half as common (25% vs. 49%) in the chemotherapy group. Liver resection operative time was equivalent (270 min) in the two groups. Higher estimated blood loss (EBL) (1,000 ml vs. 850 ml), but fewer transfusions (23% vs. 15%) were associated with the chemotherapy group. Although not statistically significant, post-operative liver enzyme peaks were higher in the chemotherapy group (AST = 402 U/L vs. 302 U/L, P = 0.09 and ALT = 433 U/L vs. 312 U/L, P = 0.1). Peak changes in INR and serum bilirubin did not differ. Complications and length of stay (LOS) did not differ between the groups. The only post-operative death was in the non-chemotherapy group. Interestingly, hepatic steatosis was present in 28% of the non-chemotherapy cases and 57% of the chemotherapy resection specimens (P = 0.005) and was marked (>30%) in 7% and 10%, respectively. Further analysis of the chemotherapy group based on the interval between completion of chemotherapy and the hepatic resection (<6 months, 7-12 months, 1-2 years, and >2 years) revealed a trend towards worse outcomes in most categories for those in the >2 years cohort. When comparing the 5-FU/LV alone, to the CPT-11 group there were no significant differences except higher intra-operative blood loss in the group receiving 5-FU/LV alone (1,295 ml vs. 756 ml, P = 0.01).

CONCLUSION

Despite variations in biochemical function and hepatic steatosis, short-term clinical outcomes are not affected by the administration of chemotherapy prior to hepatic resection. Furthermore, there is no detrimental effect of close timing of chemotherapy prior to resection, and there are no appreciable differences between irinotecan containing regimes and more traditional 5-FU-only based therapies, although the subset sample sizes were small in this study.

摘要

背景

全身化疗在结直肠癌患者中的应用越来越广泛。既往全身辅助化疗或姑息化疗对肝转移灶切除术后发病率的影响尚不明确。

目的

评估全身化疗对结直肠癌肝转移灶肝切除围手术期的影响。

方法

回顾了2001年7月至2003年7月期间进行的96例结直肠癌肝转移灶切除术(93%≥2个肝段)。前瞻性收集术前人口统计学资料、围手术期特征和术后结果。分析化疗类型以及化疗与肝切除的时间关系。

结果

96例患者中有53例(55%)在肝切除术前平均接受了5.7个周期(6.1个月)的全身化疗,从化疗结束到肝切除的中位间隔时间为12个月(范围1 - 75个月)。35例仅接受氟尿嘧啶/亚叶酸钙(5-FU/LV),9例除5-FU/LV外还接受了伊立替康(CPT-11),9例未明确说明。化疗组和未化疗组的术前年龄、性别、合并症、美国麻醉医师协会(ASA)评分、生化和肝酶谱、肿瘤数量以及肝切除范围和技术相同。化疗组的平均肿瘤大小较小(4.5 cm对5.8 cm),同时性转移的发生率为未化疗组的一半(25%对49%)。两组肝切除手术时间相当(270分钟)。化疗组估计失血量(EBL)较高(1000 ml对850 ml),但输血较少(23%对15%)。虽然无统计学意义,但化疗组术后肝酶峰值较高(谷草转氨酶[AST]=402 U/L对302 U/L,P = 0.09;谷丙转氨酶[ALT]=433 U/L对312 U/L,P = 0.1)。国际标准化比值(INR)和血清胆红素的峰值变化无差异。两组并发症和住院时间(LOS)无差异。唯一的术后死亡发生在未化疗组。有趣的是,28%的未化疗病例和57%的化疗切除标本存在肝脂肪变性(P = 0.005),分别有7%和10%的标本肝脂肪变性明显(>30%)。根据化疗结束至肝切除的间隔时间(<6个月、7 - 12个月、1 - 2年和>2年)对化疗组进行进一步分析发现,>2年队列中的大多数类别预后有变差趋势。比较单纯5-FU/LV组和CPT-11组,除单纯接受5-FU/LV组术中失血量较多外(1295 ml对756 ml,P = 0.01),无显著差异。

结论

尽管生化功能和肝脂肪变性存在差异,但肝切除术前给予化疗并不影响短期临床结果。此外,化疗与肝切除时间接近并无有害影响,含伊立替康方案与更传统的单纯5-FU方案之间无明显差异,尽管本研究中的亚组样本量较小。

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