Annals of Surgery：异体输血增加结直肠癌术后不良结局风险

《外科学年鉴》8月刊发表的一项纳入55项研究的Meta分析表明，围手术期异体输血(ABT)可显著增加结直肠癌手术患者死亡、术后感染以及其他不良临床结局风险(Ann. Surg. 2012;256:235-44)。

英国诺丁汉大学女王医学中心消化疾病治疗中心的Austin G. Acheson博士及其同事查阅了2004年12月~2010年10月间发表的12项前瞻性研究和43项回顾性队列研究，包括了术后平均随访时间约为5年的20,795例结直肠癌手术患者，其中近60%(12,242例)的患者接受平均3个单位的异体红细胞输注。

结果显示，接受输注的患者年龄相对较大，女性、直肠手术(相对于右或左结肠手术)、手术失血量较多以及Dukes 分期较差的患者输注率明显较高。在考察全因死亡率的29项研究中，异体血液输注者与未输注者全因死亡率分别为45%和35%，前者风险显著增加72%；校正观察持续时间后，年全因死亡率分别为9%和6.5%。在考察癌症相关死亡率的17项研究中，两组患者分别为31%和24%，前者风险增加71%；校正观察时间后，年癌症相关死亡率分别为5.4%和4%。在考察复发/转移死亡率复合终点的19项研究中，两组分别为43%和33%，前者风险增加66%。在12项考察术后感染风险的研究中，两组分别为29%和11%，前者风险增加3倍多。在2项考察需要再次手术干预的研究中，前者风险增加4倍。在考察住院时间的4项研究中，平均住院时间分别为18天和14天。上述所有ABT与不良临床结局的相关性均具有统计学意义。

基于该项Meta分析和其他研究证据，术前贫血是结肠手术不良预后的独立风险因素。根据该项Meta分析所显示的ABT与不良临床结局的相关性，作者声称，适当的血液处置措施对于结直肠癌择期手术患者非常重要。由于治疗水平的提高，在过去25年中ABT的应用已有所减少，但作者认为还应进一步努力以减少ABT的应用。此外，尚需开展设计良好的研究“以确定术前贫血纠正措施而非ABT是否不仅有益于结直肠癌外科领域发展，还有助于改善患者临床结局，以及哪些患者适宜采取这一措施。”

该研究得到专门致力于铁缺乏药物研制的Vifor制药公司的无限制研究经费资助。作者报告接受Vifor、爱惜康、强生以及阿斯利康等公司的咨询或代言酬金和(或)交通补助，其所在研究单位得到Vifor等公司的基金支持。

By: ELIZABETH MECHCATIE, Oncology Practice

The risks of death, postoperative infection, and other adverse clinical outcomes were significantly increased among patients undergoing colorectal cancer surgery who received perioperative allogeneic blood transfusions, according to a meta-analysis of 55 studies published in the August issue of Annals of Surgery.

Dr. Austin G. Acheson of the Nottingham (England) Digestive Disease Center at Queen’s Medical Centre and his associates reviewed 12 prospective studies and 43 retrospective cohort studies published between December 2004 and October 2010. The studies included 20,795 patients who were followed for a mean of about 5 years after undergoing surgery for colorectal cancer. Almost 60% (12,242) of these patients received a mean of three units of allogeneic red blood cells (Ann. Surg. 2012;256:235-44).

Patients who were transfused tended to be older, and the transfusion rate was significantly higher in women, those undergoing rectal surgery (compared with those undergoing right or left colon surgery), those with greater surgical blood loss, and those with worsening Dukes stage.

All associations between ABT and the adverse clinical outcomes described below were statistically significant.

The rates of all-cause mortality in the 29 studies that looked at this outcome were 45% among the patients who received blood transfusions vs. 35% of those who did not, a significant difference that represented a 72% increased risk. After adjusting for the duration of the observation period, the investigators found that the annual incidence of all-cause mortality was almost 9% among the transfused patients vs. 6.5% among those who were not transfused.

The rate of cancer-related mortality was 31% vs. 24% in the 17 studies that measured this outcome, a 71% increased risk. After adjusting for the length of observation, the investigators said the annual incidence of cancer-related mortality was 5.4% of those transfused and 4% of those who were not.

The rate of the combined end point of death resulting from recurrence/metastasis was 43% of those who were transfused vs. 33% of those who were not transfused – a 66% increase in risk – in the 19 studies that measured this outcome.

The risk of postoperative infections in the 12 studies that measured this outcome was 29% among those who were transfused vs. 11% of those who were not transfused, which was more than a threefold increased risk. In the two studies that measured the need for surgical reintervention, the risk was increased fourfold among those who were transfused.

In the four studies that measured the length of hospitalization, the hospital stay was a mean of almost 18 days among those who received transfusions, compared with 14 days among those who did not.

Based on evidence in this meta-analysis and other studies showing that preoperative anemia is an independent risk factor for a worse prognosis after colon surgery, and based on the association between ABTs and poorer clinical outcomes in this meta-analysis, the authors wrote that "appropriate blood management measures should, therefore, be given an important place in the care of patients with CRC [colorectal cancer] undergoing elective surgery."

The use of ABT has dropped over the past 25 years because of improvements in patient care, and the authors stated that they believe efforts should be made to further minimize ABT use. Well-designed studies are needed "to determine whether and in which patients preoperative corrective measures of anemia, other than ABTs, will contribute not only in the field of colorectal surgery but also to improve clinical outcomes," they added.

The study was supported by an unrestricted research grant from Vifor Pharma AG, a specialty pharmaceuticals company focused on the treatment of iron deficiency, according to its website. The authors disclosed receiving honoraria and/or travel support for consulting or lecturing for companies that include Vifor, Ethicon Endosurgery, Johnson & Johnson, and AstraZeneca AG; their research departments received grant support from companies that included Vifor.