The Impact of Blood Transfusion on Recurrence and Mortality Following Colorectal Cancer Resection: A Propensity Score Analysis of 4,030 Patients

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Abstract

Whether blood transfusion exacerbates cancer outcomes after surgery in humans remains inconclusive. We utilized a large cohort to investigate the effect of perioperative blood transfusion on cancer prognosis following colorectal cancer (CRC) resection. Patients with stage I through III CRC undergoing tumour resection at a tertiary medical center between 2005 and 2014 were identified and evaluated through August 2016. Propensity score matching was used to cancel out imbalances in patient characteristics. Postoperative disease-free survival (DFS) and overall survival (OS) were analysed using Cox regression model. A total of 4,030 and 972 patients were analysed before and after propensity score matching. Cox regression analyses demonstrated blood transfusion associated with shorter DFS and OS before and after matching (hazard ratio: 1.41, 95% CI: 1.2–1.66 for DFS; 1.97, 95% CI: 1.6–2.43 for OS). Larger transfusion volume was linked to higher overall mortality (≤4 units vs. nil, HR = 1.58; >4 units vs. nil, HR = 2.32) but not more cancer recurrence. Preoperative anemia was not associated with decreased survival after adjusting covariates. Perioperative blood transfusion was associated with worse cancer prognosis after curative colorectal resection, independently of anemia status. Strategies aimed at minimizing transfusion requirements should be further developed.

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Most cited references 20

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Prognostic factors in colorectal cancer. College of American Pathologists Consensus Statement 1999.

James D. Sargent, R D Nagle, Katherine Fielding … (2000)

Under the auspices of the College of American Pathologists, the current state of knowledge regarding pathologic prognostic factors (factors linked to outcome) and predictive factors (factors predicting response to therapy) in colorectal carcinoma was evaluated. A multidisciplinary group of clinical (including the disciplines of medical oncology, surgical oncology, and radiation oncology), pathologic, and statistical experts in colorectal cancer reviewed all relevant medical literature and stratified the reported prognostic factors into categories that reflected the strength of the published evidence demonstrating their prognostic value. Accordingly, the following categories of prognostic factors were defined. Category I includes factors definitively proven to be of prognostic import based on evidence from multiple statistically robust published trials and generally used in patient management. Category IIA includes factors extensively studied biologically and/or clinically and repeatedly shown to have prognostic value for outcome and/or predictive value for therapy that is of sufficient import to be included in the pathology report but that remains to be validated in statistically robust studies. Category IIB includes factors shown to be promising in multiple studies but lacking sufficient data for inclusion in category I or IIA. Category III includes factors not yet sufficiently studied to determine their prognostic value. Category IV includes factors well studied and shown to have no prognostic significance. The medical literature was critically reviewed, and the analysis revealed specific points of variability in approach that prevented direct comparisons among published studies and compromised the quality of the collective data. Categories of variability recognized included the following: (1) methods of analysis, (2) interpretation of findings, (3) reporting of data, and (4) statistical evaluation. Additional points of variability within these categories were defined from the collective experience of the group. Reasons for the assignment of an individual prognostic factor to category I, II, III, or IV (categories defined by the level of scientific validation) were outlined with reference to the specific types of variability associated with the supportive data. For each factor and category of variability related to that factor, detailed recommendations for improvement were made. The recommendations were based on the following aims: (1) to increase the uniformity and completeness of pathologic evaluation of tumor specimens, (2) to enhance the quality of the data needed for definitive evaluation of the prognostic value of individual prognostic factors, and (3) ultimately, to improve patient care. Factors that were determined to merit inclusion in category I were as follows: the local extent of tumor assessed pathologically (the pT category of the TNM staging system of the American Joint Committee on Cancer and the Union Internationale Contre le Cancer [AJCC/UICC]); regional lymph node metastasis (the pN category of the TNM staging system); blood or lymphatic vessel invasion; residual tumor following surgery with curative intent (the R classification of the AJCC/UICC staging system), especially as it relates to positive surgical margins; and preoperative elevation of carcinoembryonic antigen elevation (a factor established by laboratory medicine methods rather than anatomic pathology). Factors in category IIA included the following: tumor grade, radial margin status (for resection specimens with nonperitonealized surfaces), and residual tumor in the resection specimen following neoadjuvant therapy (the ypTNM category of the TNM staging system of the AJCC/UICC). (ABSTRACT TRUNCATED)

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Perineural invasion is an independent predictor of outcome in colorectal cancer.

Daniel J. Wilks, H. Berger, Catherine Liebig … (2009)

Perineural invasion (PNI) is associated with decreased survival in several malignancies, but its significance in colorectal cancer (CRC) remains to be clearly defined. We evaluated PNI as a potential prognostic indicator in CRC, focusing on its significance in node-negative patients. We identified 269 consecutive patients who had CRC resected at our institution. Tumors were re-reviewed for PNI by a pathologist blinded to the patients' outcomes. Overall and disease-free survivals were determined using the Kaplan-Meier method, with differences determined by multivariate analysis using the Cox multiple hazards model. Results were compared using the log-rank test. PNI was identified in less than 0.5% of the initial pathology reports. On rereview, 22% of tumors in our series were found to be PNI positive. The 5-year disease-free survival rate was four-fold greater for patients with PNI-negative tumors versus those with PNI-positive tumors (65% v 16%, respectively; P < .0001). The 5-year overall survival rate was 72% for PNI-negative tumors versus 25% for PNI-positive tumors. On multivariate analysis, PNI was an independent prognostic factor for both cancer-specific overall and disease-free survival. In a subset analysis comparing patients with node-negative disease with patients with stage III disease, the 5-year disease-free survival rate was 56% for stage III patients versus 29% for patients with node-negative, PNI-positive tumors (P = .0002). Similar results were seen for overall survival. PNI is grossly underreported in CRC and could serve as an independent prognostic factor of outcomes in these patients. PNI should be considered when stratifying CRC patients for adjuvant treatment.

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Inflammatory response, immunosuppression, and cancer recurrence after perioperative blood transfusions.

Juan Cata, Sruthima N. V. S. Gottumukkala, D Sessler … (2013)

Debate on appropriate triggers for transfusion of allogeneic blood products and their effects on short- and long-term survival in surgical and critically ill patients continue with no definitive evidence or decisive resolution. Although transfusion-related immune modulation (TRIM) is well established, its influence on immune competence in the recipient and its effects on cancer recurrence after a curative resection remains controversial. An association between perioperative transfusion of allogeneic blood products and risk for recurrence has been shown in colorectal cancer in randomized trials; whether the same is true for other types of cancer remains to be determined. This article focuses on the laboratory, animal, and clinical evidence to date on the mechanistic understanding of inflammatory and immune-modulatory effects of blood products and their significance for recurrence in the cancer surgical patient.

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Author and article information

Contributors

Kuang-Yi Chang: kychang@vghtpe.gov.tw

Journal

Journal ID (nlm-ta): Sci Rep

Journal ID (iso-abbrev): Sci Rep

Title: Scientific Reports

Publisher: Nature Publishing Group UK (London )

ISSN (Electronic): 2045-2322

Publication date (Electronic): 6 September 2018

Publication date PMC-release: 6 September 2018

Publication date Collection: 2018

Volume: 8

Electronic Location Identifier: 13345

Affiliations

[1 ]ISNI 0000 0004 0604 5314, GRID grid.278247.c, Department of Anesthesiology, , Taipei Veterans General Hospital, ; Taipei, Taiwan

[2 ]ISNI 0000 0004 0604 5314, GRID grid.278247.c, Department of Surgery, , Taipei Veterans General Hospital, ; Yuli Branch, Hualien Taiwan

[3 ]ISNI 0000 0001 0425 5914, GRID grid.260770.4, School of Medicine, , National Yang-Ming University, ; Taipei, Taiwan

[4 ]ISNI 0000 0000 9337 0481, GRID grid.412896.0, Department of Anesthesiology, , Shuang Ho Hospital, Taipei Medical University, ; New Taipei City, Taiwan

[5 ]ISNI 0000 0000 9337 0481, GRID grid.412896.0, Department of Anesthesiology, , School of Medicine, College of Medicine, Taipei Medical University, ; Taipei, Taiwan

[6 ]ISNI 0000 0001 2158 7670, GRID grid.412090.e, Department of Technology Application and Human Resource Development, , National Taiwan Normal University, ; Taipei, Taiwan

[7 ]ISNI 0000 0004 0546 0241, GRID grid.19188.39, Division of Biostatistics, Graduate Institute of Epidemiology and Preventive Medicine, , College of Public Health, National Taiwan University, ; Taipei, Taiwan

Article

Publisher ID: 31662

DOI: 10.1038/s41598-018-31662-5

PMC ID: 6127303

PubMed ID: 30190571

SO-VID: 2a147b9f-0fae-40ee-9763-336ab7241428

License:

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

History

Date received : 21 March 2018

Date accepted : 14 August 2018

Funding

Funded by: FundRef https://doi.org/10.13039/501100004663, Ministry of Science and Technology, Taiwan (Ministry of Science and Technology of Taiwan);

Award ID: MOST104-2314-B-075-015

Award Recipient : Hsiang-Ling Wu Ying-Hsuan Tai Shih-Pin Lin Min-Ya Chan Hsiu-Hsi Chen

Funded by: Taipei Veterans General Hospital (V104C-096)

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The Impact of Blood Transfusion on Recurrence and Mortality Following Colorectal Cancer Resection: A Propensity Score Analysis of 4,030 Patients

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Abstract

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Most cited references 20

Prognostic factors in colorectal cancer. College of American Pathologists Consensus Statement 1999.

Perineural invasion is an independent predictor of outcome in colorectal cancer.

Inflammatory response, immunosuppression, and cancer recurrence after perioperative blood transfusions.

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Cited by 42

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