A Amato1, M Pescatori. 1. Sigma Tau Research, Inc., 10101 Grosvenor Place, apartment#1415, Rockville, Maryland 20852, USA. Antonino.Amato@st-research.com
Abstract
BACKGROUND: The improvement of renal allograft survival by pre-transplantation transfusions alerted the medical community to the potential detrimental effect of transfusions in patients being treated for cancer. OBJECTIVES: The present meta-analysis aims to evaluate the role of perioperative blood transfusions (PBT) on colorectal cancer recurrence. This is accomplished by validating the results of a previously published meta-analysis (Amato 1998); and by updating it to December 2004. SEARCH STRATEGY: Published papers were retrieved using Medline, EMBASE, the Cochrane Library, controlled trials web-based registries, or the CCG Trial Database. The search strategy used was: {colon OR rectal OR colorectal} WITH {cancer OR tumor OR neoplasm} AND transfusion. The tendency not to publish negative trials was balanced by inspecting 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 any amount of blood products within one month of surgery. Excluded were patients with distant metastases at surgery, and studies with short follow-up or with no data. DATA COLLECTION AND ANALYSIS: A specific form was developed for data collection. Data extraction was cross-checked, using the most recent publication in case of repetitive ones. Papers' quality was ranked 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 4.2). When available, data were stratified for risk factors of cancer recurrence. MAIN RESULTS: The findings of the 1998 meta-analysis were confirmed, with small variations in some estimates. Updating it through December 2004 led to the identification of 237 references. Two-hundred and one of them were excluded because they analyzed survival (n=22), were repetitive (n=26), letters/reviews (n=66) or had no data (n=87). Thirty-six studies on 12,127 patients were included: 23 showed a detrimental effect of PBT; 22 used also multivariable analyses, and 14 found PBT to be an independent prognostic factor. Pooled estimates of PBT effect on colorectal cancer recurrence yielded overall OR of 1.42 (95% CI, 1.20 to 1.67) against transfused patients in randomized controlled studies. Stratified meta-analyses confirmed these findings, also when stratifying patients by site and stage of disease. The PBT effect was observed 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. All analyses support the hypothesis that PBT have a detrimental effect on the recurrence of curable colorectal cancers. However, since heterogeneity was detected and conclusions on the effect of surgical technique could not be drawn, a causal relationship cannot still be claimed. Carefully restricted indications for PBT seems necessary.
BACKGROUND: The improvement of renal allograft survival by pre-transplantation transfusions alerted the medical community to the potential detrimental effect of transfusions in patients being treated for cancer. OBJECTIVES: The present meta-analysis aims to evaluate the role of perioperative blood transfusions (PBT) on colorectal cancer recurrence. This is accomplished by validating the results of a previously published meta-analysis (Amato 1998); and by updating it to December 2004. SEARCH STRATEGY: Published papers were retrieved using Medline, EMBASE, the Cochrane Library, controlled trials web-based registries, or the CCG Trial Database. The search strategy used was: {colon OR rectal OR colorectal} WITH {cancer OR tumor OR neoplasm} AND transfusion. The tendency not to publish negative trials was balanced by inspecting 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 any amount of blood products within one month of surgery. Excluded were patients with distant metastases at surgery, and studies with short follow-up or with no data. DATA COLLECTION AND ANALYSIS: A specific form was developed for data collection. Data extraction was cross-checked, using the most recent publication in case of repetitive ones. Papers' quality was ranked 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 4.2). When available, data were stratified for risk factors of cancer recurrence. MAIN RESULTS: The findings of the 1998 meta-analysis were confirmed, with small variations in some estimates. Updating it through December 2004 led to the identification of 237 references. Two-hundred and one of them were excluded because they analyzed survival (n=22), were repetitive (n=26), letters/reviews (n=66) or had no data (n=87). Thirty-six studies on 12,127 patients were included: 23 showed a detrimental effect of PBT; 22 used also multivariable analyses, and 14 found PBT to be an independent prognostic factor. Pooled estimates of PBT effect on colorectal cancer recurrence yielded overall OR of 1.42 (95% CI, 1.20 to 1.67) against transfused patients in randomized controlled studies. Stratified meta-analyses confirmed these findings, also when stratifying patients by site and stage of disease. The PBT effect was observed 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. All analyses support the hypothesis that PBT have a detrimental effect on the recurrence of curable colorectal cancers. However, since heterogeneity was detected and conclusions on the effect of surgical technique could not be drawn, a causal relationship cannot still be claimed. Carefully restricted indications for PBT seems necessary.
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