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      Preoperative anemia in colorectal cancer: relationships with tumor characteristics, systemic inflammation, and survival

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          Abstract

          Anemia is common in colorectal cancer (CRC) but its relationships with tumor characteristics, systemic inflammation, and survival have not been well characterized. In this study, blood hemoglobin levels and erythrocyte mean corpuscular volume (MCV) levels were measured in two independent cohorts of 148 CRC patients and 208 CRC patients, and their correlation with patient and tumor characteristics, systemic inflammatory markers (modified Glasgow Prognostic Score: mGPS; serum levels of thirteen cytokines, C-reactive protein, albumin), and survival were analyzed. We found that anemia, most frequently normocytic, followed by microcytic, was present in 43% of the patients. Microcytic anemia was most commonly associated with proximal colon tumor location. Average MCV and blood hemoglobin levels were lower in tumors with high T-class. Low blood hemoglobin associated with systemic inflammation, including high mGPS and high serum levels of C-reactive protein and IL-8. Particularly, normocytic anemia associated with higher mGPS. Normocytic anemia associated with a tendency towards worse overall survival (multivariate hazard ratio 1.61, 95% confidence interval 1.07–2.42, p = 0.023; borderline statistical significance considering multiple hypothesis testing). In conclusion, anemia in CRC patients is most frequently normocytic. Proximal tumor location is associated with predominantly microcytic anemia and systemic inflammation is associated with normocytic anemia.

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          The systemic inflammation-based Glasgow Prognostic Score: a decade of experience in patients with cancer.

          Since the initial work, a decade ago that the combination of C-reactive protein and albumin, the Glasgow Prognostic Score (GPS), had independent prognostic value in patients with cancer, there have been more than 60 studies (>30,000 patients) that have examined and validated the use of the GPS or the modified GPS (mGPS) in a variety of cancer scenarios. The present review provides a concise overview of these studies and comments on the current and future clinical utility of this simple objective systemic inflammation-based score. The GPS/mGPS had independent prognostic value in (a) unselected cohorts (4 studies, >19,400 patients) (b) operable disease (28 studies, >8,000 patients) (c) chemo/radiotherapy (11 studies, >1500 patients) (d) inoperable disease (11 studies, >2,000 patients). Association studies (15 studies, >2,000 patients) pointed to an increased GPS/mGPS being associated with increased weight and muscle loss, poor performance status, increased comorbidity, increased pro-inflammatory and angiogenic cytokines and complications on treatment. These studies have originated from 13 different countries, in particular the UK and Japan. A chronic systemic inflammatory response, as evidenced by the GPS/mGPS, is clearly implicated in the prognosis of patients with cancer in a variety of clinical scenarios. The GPS/mGPS is the most extensively validated of the systemic inflammation-based prognostic scores and therefore may be used in the routine clinical assessment of patients with cancer. It not only identifies patients at risk but also provides a well defined therapeutic target for future clinical trials. It remains to be determined whether the GPS has prognostic value in other disease states. Copyright © 2012 Elsevier Ltd. All rights reserved.
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            Anemia as an independent prognostic factor for survival in patients with cancer: a systemic, quantitative review.

            Anemia is common in cancer patients, although the prevalence is influenced both by the type of malignancy and the choice of treatment. Individual studies have compared the survival of patients with and without anemia and have shown reduced survival times in patients with various malignancies, including carcinoma of the lung, cervix, head and neck, prostate, lymphoma, and multiple myeloma. The objective of this study was to systematically review, to summarize, and to obtain an overall estimate of the effect of anemia on survival in patients with malignant disease. A comprehensive literature review was carried out using the MEDLINE data base and reviewing the reference lists from published studies. Two hundred papers were identified. Of these, 60 papers that reported the survival of cancer patients according to either hemoglobin levels or the presence of anemia were included. Among these papers, 25% related to patients with lung carcinoma, 17% related to patients with head and neck carcinoma, 12% related to patients with multiple myeloma, 10% related to patients with prostate carcinoma, 8% related to patients with cervicouterine carcinoma, 7% related to patients with leukemia, 5% related to patients with lymphoma, and 16% related to patients with other types of malignancies. The relative risk of death increased by 19% (95% confidence interval, 10-29%) in anemic patients with lung carcinoma, by 75% (37-123%) in anemic patients with head and neck carcinoma, by 47% (21-78%) in anemic patients with prostate carcinoma, and by 67% (30-113%) in anemic patients with lymphoma. The overall estimate increase in risk was 65% (54-77%). Anemia is associated with shorter survival times for patients with lung carcinoma, cervicouterine carcinoma, head and neck carcinoma, prostate carcinoma, lymphoma, and multiple myeloma. Copyright 2001 American Cancer Society.
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              Prevalence and outcomes of anemia in cancer: a systematic review of the literature.

              Anemia is common in patients with cancer. This systematic literature review of reports published in 1966 through February 2003 identified the prevalence of anemia in specific cancers and assessed the impact of anemia on survival and quality of life (QOL). Studies about chemotherapy-induced anemia were excluded. Anemia prevalence varied widely; most studies found that between 30% and 90% of patients with cancer had anemia. Prevalence was affected strongly by the definition of anemia: 7% of patients with Hodgkin disease had anemia when the condition was defined as a hemoglobin level <90.0 g/L; as many as 86% of patients had anemia when it was defined as a hemoglobin value <110.0 g/L. Prevalence varied by cancer type and disease stage: 40% of patients with early-stage colon tumors and nearly 80% of patients with advanced disease had anemia. Patients with anemia had poorer survival and local tumor control than did their nonanemic counterparts in 15 of 18 studies. In 8 of 12 studies, patients without anemia (most treated with epoetin) needed fewer transfusions. QOL was positively correlated with hemoglobin levels in 15 of 16 studies. There was no significant difference in treatment toxicity between patients with and without anemia. Tumor hypoxia, which has been associated with resistance to radiation therapy and chemotherapy, may stimulate angiogenesis, leading to poor local control of tumors and increased morbidity and mortality. Treatment of anemia may have a significant impact on patient survival and QOL. However, a standard definition of anemia is needed, as is research about the effect of anemia on cancer progression.
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                Author and article information

                Contributors
                juha.vayrynen@oulu.fi
                Journal
                Sci Rep
                Sci Rep
                Scientific Reports
                Nature Publishing Group UK (London )
                2045-2322
                18 January 2018
                18 January 2018
                2018
                : 8
                : 1126
                Affiliations
                [1 ]ISNI 0000 0001 0941 4873, GRID grid.10858.34, Cancer and Translational Medicine Research Unit, , University of Oulu, POB 5000, ; Oulu, 90014 Finland
                [2 ]ISNI 0000 0004 4685 4917, GRID grid.412326.0, Department of Pathology, , Oulu University Hospital and Medical Research Center Oulu, Oulu, POB 21, ; Oulu, 90029 Finland
                [3 ]ISNI 0000 0001 0941 4873, GRID grid.10858.34, Research Unit of Surgery, , Anesthesia and Intensive Care, University of Oulu, POB 5000, ; Oulu, 90014 Finland
                [4 ]ISNI 0000 0004 4685 4917, GRID grid.412326.0, Department of Surgery, , Oulu University Hospital and Medical Research Center Oulu, POB 21, ; Oulu, 90029 Finland
                [5 ]ISNI 0000 0001 0941 4873, GRID grid.10858.34, Research Unit of Biomedicine and Biocenter of Oulu, , University of Oulu, POB 5000, ; Oulu, 90014 Finland
                [6 ]ISNI 0000 0004 4685 4917, GRID grid.412326.0, Oulu University Hospital and Medical Research Center Oulu, POB 21, ; Oulu, 90029 Finland
                [7 ]ISNI 0000 0001 2205 0971, GRID grid.22254.33, Department of Gastroenterology and Metabolism, , Poznan University of Medical Sciences, ul. Szpitalna 27/33, ; 60-572 Poznan, Poland
                Article
                19572
                10.1038/s41598-018-19572-y
                5773501
                29348549
                411b2167-6727-424c-b527-188da7dcd06f
                © The Author(s) 2018

                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/.

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                : 17 August 2017
                : 4 January 2018
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