Perioperative blood transfusions and recurrence of colorectal cancer

 

Abstract

Background

The improvement of renal allograft survival by pre-transplantation transfusions alerted to the potential detrimental effect of transfusions in cancer treatment.

Objectives

This meta-analysis evaluates the role of perioperative blood transfusions (PBT) on colorectal cancer recurrence. This is accomplished by updating the results of a previously published meta-analysis (Amato 2006) to December 2009.

Search methods

Papers were retrieved using Medline, EMBASE, the Cochrane Library, trials web-based registries, or the CCG Database. The search strategy was: {colon OR rectal OR colorectal} WITH {cancer OR tumor OR neoplasm} AND transfusion. The publication bias was balanced by reviewing the proceedings of international congresses.

Selection criteria

Patients undergoing curative resection of colorectal cancer (classified either as Dukes stages A-C, Astler-Coller stages A-C2, or TNM stages T1-3a/N0-1/M0) were included if they had received blood products within one month of surgery. Excluded were patients with distant metastases and studies with short follow-up or no data.

Data collection and analysis

A specific form was used for data collection. Data was cross-checked, using the most recent publication in case of repetitive ones. Papers' quality was evaluated using the method by Evans and Pollock. Odds ratios (OR, with 95% confidence intervals) were computed for each study, and pooled estimates were generated by RevMan (version 5). When available, data were stratified for risk factors of cancer recurrence.

Main results

Updating the previous review through December 2009 identified 41 additional papers, for a grand total of 278 references. Two-hundred and fourty-two of them were excluded because they analyzed survival (n=27), were repetitive (n=29), letters/reviews (n=71) or had no data (n=115). Thirty-six studies on 12,127 patients remained included: 23 showed a detrimental effect of PBT; 22 used multivariable analyses, and 14 found an independent PBT effect. Pooled estimates of PBT effect on recurrence in randomised studies yielded an OR of 1.42 (95% CI, 1.20 to 1.67) against transfused patients. Stratified meta-analyses confirmed these findings also by site and stage of disease, regardless of timing, type, and in a dose-related fashion, although heterogeneity was detected. Data on surgical techniques was not available for further analysis.

Authors' conclusions

This updated meta-analysis confirms the previous findings and supports the association of PBT on the recurrence of curable colorectal cancers. However, since heterogeneity was detected and the effect of surgical technique could not be assessed, a causal relationship cannot still be claimed. Carefully restricted indications for PBT seems necessary.

 

Plain language summary

Does perioperative blood transfusion affect the recurrence rate of potentially curable operations for colorectal cancer?

This review include 36 studies, identified from 278 references retrieved until December 2009, and report a moderate association between colorectal cancer recurrence and perioperative transfusions, with an OR of 1.42 (95% CI, 1.20 to 1.67). Similar estimates are present in several subgroup meta-analyses, as well as in meta-analyses stratified for known risk factors. These findings support carefully restricted indications for perioperative blood transfusions in colorectal cancer patients operated for cure, and continue to await the results of studies addressing the role of surgeon-related risk factors on the need for transfusion and disease recurrence.

 

摘要

背景

手術期間輸血(Perioperative blood transfusion)對於大腸癌復發的影響

進行移植前輸血對於腎臟移植存活率的改善提醒了醫界到對於正在接受癌症治療的患者來說，輸血可能造成的潛在不良影響

目標

本研究的主要目的在於藉由現有後設分析來評估手術期間輸血(perioperative blood transfusions，PBT)對於大腸癌復發的影響，這個方法會伴隨著先前已公開後的試驗的有效結果(1998年)，並且更新到2004年12月的數據

搜尋策略

利用Medline、EMBASE、Cochrane Library、對照試驗網路版(controlled trials webbased registries)或是CCG Trial Database等資料庫進行檢索以確認納入本研究的公開文獻，檢索策略包括使用下列關鍵字：「{colon OR rectal OR colorectal} WITH {cancer OR tumor OR neoplasm} AND transfusion」，不公開負面試驗的傾向會因為受到正在進行中的國際會議所審視而達到平衡效果

選擇標準

接受大腸癌治癒性切除(分類為Dukes階段Ａ至Ｃ，AstlerColler階段A至C2或是TNM階段T1−3a/N0−1/M0)，且如果有在手術的1個月內接受任何數量血液產品的患者都會被納入研究中，在手術期間發生病患已經出現遠端轉移現象、研究後追蹤時間過短或是缺乏數據都會被排除於試驗之外

資料收集與分析

我們發展出一種特別的表格來蒐集數據，數據萃取的工作會使用最新公開的方法進行交叉確認以預防取用重複的數據，文獻的品質則是使用Evans和Pollock所訂定的方法加以評分，每個試驗的OR值(配合95％信心區間進行表示)會以電腦進行運算，整體的計算都透過RevMan(4.2版本)軟體來進行，在可行的前提下，數據會被分層以評估癌症復發的風險因子。

主要結論

本研究中有1998個後設分析被確認，在某些估算中的變異十分微小，在2004年12月進行的更新可以確認237篇參考文獻，有201試驗因為是針對存活率(22篇)、重複試驗(26篇)、屬於信函或文獻回顧形式(66篇)和缺乏數據(87篇)而被排除於研究之外，有36個試驗針對12127名患者進行測試被納入本研究中：其中有23個試驗顯示PBT對於患者有不利影響；有22個試驗使用多變異數分析分法；有14個試驗發現PBT是一個獨立的預後因子(prognostic factor)，針對PBT對於大腸癌復發的影響進行整合性的分析，相對於隨機性對照試驗接受輸血的患者來說，其整體性OR值為1.42(95％的信心區間介於1.20至1.67之間)。分層的後設分析結果確認了這個發現，其中患者係依據疾病的部位及程度進行分級，無論時間、癌症種類，都可觀察到PBT的影響，並與劑量有關，但是仍有檢測到試驗之間的異質性。由手術技術的數據並無法用來進行更進一步的分析

作者結論

本次更新的後設分析確認了先前的研究發現，所有的分析都支持有關於PBT是一種對大腸直腸癌治癒後復發的不利因子的推論，但是因為異質性的存在，因此無法針對手術的影響進行結論，也不能明確歸納出其中的相互關係，似乎有必要小心的限制PBT的使用

翻譯人

此翻譯計畫由臺灣國家衛生研究院(National Health Research Institutes, Taiwan)統籌

總結

是否進行手術中輸血會影響大腸直腸癌手術痊癒後癌細胞的復發率？至2004年12月為止，本研究由確認的237個參考文獻資料納入了36個試驗，並且提出在大腸直腸癌復發率和手術中輸血之間距有中度的「相關性」，OR值為.42(95％的信心區間介於1.20至1.67之間)，在所有次分組的後設分析結果中也出現類似的結果，對於已知風險因子的分組後設分析中也是如此，這些發現應該在大腸直腸癌患者的手術過程中至痊癒這段時間內需要小心且有限制的使用輸血，並且等待更多可以說明手術相關風險因子對於輸血需求及疾病復發率中所扮演角色的試驗結果