key: cord-0726326-sqk1t2tg authors: Mungan, İbrahim; Bostancı, Erdal Birol; Türksal, Erbil; Tezcan, Büşra; Aktaş, Mehmet Nesim; Can, Müçteba; Kazancı, Dilek; Turan, Sema title: The predictive power of C‐reactive protein‐ lymphocyte ratio for in‐hospital mortality after colorectal cancer surgery date: 2021-02-15 journal: Cancer Rep (Hoboken) DOI: 10.1002/cnr2.1330 sha: 17b8d03c932fd2967602a79d294beed6de75898a doc_id: 726326 cord_uid: sqk1t2tg BACKGROUND: The relation between immunity, inflammation, and tumor development and progression has been emphasized in colorectal cancer widely and the prognosis is linked to the inflammatory reaction of the host as well as the biological behavior of the tumor. AIM: In this study, we aimed to find out the predictive power of C‐reactive protein‐ lymphocyte ratio (CLR) for in‐hospital mortality after colorectal surgery. METHODS AND RESULTS: A series of 388 CRC patients were enrolled in the present retrospective study which was conducted in a tertiary state Hospital in Ankara, Turkey. In‐hospital mortality was the main outcome to evaluate the predictive power of inflammatory markers, while the other outcomes that would be evaluated as separate variables were LOS in hospital and LOS in ICU. In this study, there were 260 males and 128 females, and the mean age was 60.9. The in‐hospital mortality rate was 3.4% (n = 13) and age, APACHE II score and Charlson comorbidity index score were related to in‐hospital mortality statistically. The mean LOS in the hospital was 13.9 days and LOS in ICU was 4.5 days. The CRP levels and the CLR levels were higher both in the preoperative and postoperative periods in the mortality (+) group and the difference was significant statistically (P = .008/ .002 and .004/ <.001, respectively). CLR in the postoperative period had the best predictive power with AUC: 0.876. CONCLUSION: In conclusion, within the context of our study there appears to be a relationship between CLR, as measured on day 2 postoperatively, and in‐hospital mortality. It is observed to be more effective than NLR, ALC, and CRP. cases. 3 The relation between innate immunity, inflammation, and tumor development and progression have been specifically emphasized in cases of CRC arising from inflammatory bowel disease (IBD) and it is concluded that the prognosis of CRC is associated with the inflammatory reaction of the host as well as the biological behavior of the tumor. 4 The inflammatory response-tumor interaction is extending out These inflammation-related markers are either derived from complete blood count like neutrophil-lymphocyte ratio (NLR) and platelet related inflammatory markers or derived from routine laboratory tests like C-reactive protein (CRP). The most concerning inflammatory markers are NLR, platelet lymphocyte ratio (PLR), CRP, and CRPalbumin ratio (CAR), and they have been studied in a wide range of cancer, including breast cancer, CRC, lung cancer, gastric cancer, and ovarian cancer. 5, 8 The prognostic factors for colorectal cancer are well-defined as tumor stage, histological grade, lymph node status, and intravascular invasion, whereas due to the influence of systemic inflammation in CRC progression, biomarkers offer potential supplemental predictive parameters. 9, 10 In a recent study, it was stressed that neutrophil, platelet, and CRP levels were related to up-regulation in disease progression while lymphocyte and albumin values were related to down-regulation in disease progression for CRC. 11 Approximately 20% to 40% increment in the serum levels of acute-phase proteins like CRP in the case of resectable CRC was reported, while the amount of preoperative or postoperative level was correlated with poor prognosis. 7 The lymphocyte-to-monocyte ratio (LMR), the NLR, the platelet -lymphocyte ratio (PLR), and prognostic scores like modified Glasgow Prognostic Score (mGPS) and systemic inflammation score (SIS) which comprise the serum albumin levels, serum C-reactive protein (CRP) or LMR are the other investigated predictive biomarkers for prognosis in CRC cases. 9, 12, 13 In this study, we aimed to find out the predictive power of Creactive protein-lymphocyte ratio (CLR) for in-hospital mortality after colorectal surgery and to compare it with the other well-known inflammatory markers like CRP and NLR. As far as we know, Creactive protein-lymphocyte ratio (CLR) has not been investigated as a prognostic or predictive factor in the CRC cases in the literature. The other criteria for exclusion were benign pathologies like IBD or ischemia, history of other malignancies, the requirement for a second operation in the first month after CRC surgery, and clinical evidence of autoimmune disorder, systemic inflammation, or infection. All demographic and clinical data, including gender, age, Acute Physiologic Assessment, and Chronic Health Evaluation II (APACHE II) score, Charlson Comorbidity Index score, the surgical procedure, and the outcomes in the postoperative period were derived from the institutional database. Our study was designed in a retrospective manner and did not require any specific laboratory test or clinical data other than obtained data from patients' files or nurse sheets. The Between June 2015 and July 2018, 388 patients who underwent CRC surgery were included in this study after the exclusion of the 190 cases which was described in Figure 1 . There were 260 males and 128 females, and the mean age was 60.9. The demographic and descriptive variables were listed in Table 1 . The in-hospital mortality rate was 3.4% (n = 13) and age, APACHE II score and Charlson comorbidity index score were related to in-hospital mortality statistically. The location of the tumor, the histological grade, and the TNM stageeven the metastasis-did not differ between mortality (+) and mortality (−) groups statistically (P > .05). Among the 13 who died, the most The values of the chosen inflammatory markers in the preoperative period (Day 0), and the postoperative period (Day 2), the difference between postoperative and preoperative values were listed and compared according to mortality Preoperative ANC (×10 9 /l) (mean ± SD) 6.5 ± 4 8.1 ± 5.5 6.4 ± 3.9 .212 Postoperative ANC (×10 9 /l) (mean ± SD) 7.6 ± 3.9 8.9 ± 5.8 7.6 ± 3.8 .367 ANC difference (×10 9 /l) (mean ± SD) 1.1 ± 4.5 0.9 ± 4.9 1.1 ± .4.5 .798 Preoperative ALC (×10 9 /l) (mean ± SD) 1.7 ± 0.8 1.4 ± 0.5 1.7 ± 0.8 .131 Postoperative ALC (×10 9 /l) (mean ± SD) 1 common reasons for in-hospital mortality were cardiovascular disease (acute myocardial infarction and arrhythmia; n = 4), respiratory disease (pneumonia and acute exacerbation of chronic obstructive pulmonary disease; n = 6), and sepsis (n = 2). In one patient, the cause of death was acute respiratory failure after stroke. As it was described in detail in Table 2 , the operative variables like surgical procedure type and the duration of surgery, and the postoperative outcomes like the length of stay (LOS) in hospital and intensive care unit (ICU) did not differ between groups as well. The mean LOS in hospital was 13.9 days and LOS in ICU was 4.5 days. The anastomoses leak rate was 3.6% (n = 14) and did not correlate with mortality statistically (P = .423). In Table 3 The predictive power of the inflammatory markers for in-hospital mortality was compared by AUC and ROC curves in Table 4 and cancer, 20 and in CRC. 11 In the second study, he deduced that the combination of lymphocyte count along with C-reactive protein levels was more correlated with recurrence, overall survival (OS), and disease-free survival (DFS) than other biomarkers in CRC patients. 11 Also, Daldal et al 21 In conclusion, within the context of our study there appears to be a relationship between CLR, as measured on day 2 postoperatively, and in-hospital mortality. It was observed to be more effective than NLR, ALC, and CRP. Hence, the predictive power should be assessed with prospective controlled studies, but we believed that CLR has the potential to complete the missing piece of the puzzle as a prognostic biomarker in CRC patients. Besides the findings of our study, there were some limitations to conclude more specific determinations. Being a single-center, small-scale, and short-termed follow-up study were the main limitations. The retrospective and cohort nature of this study were the other limitations. Prospective multi-center studies would be more accurate to confirm these initial results. The authors of this original article certify that they have NO affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers' bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patentlicensing arrangements), or nonfinancial interest (such as personal or professional relationships, affiliations, knowledge or beliefs) in the subject matter or materials discussed in this manuscript. The authors declare that they have no competing interests or no conflict of interest. Because our study was in the category of noninterventional clinical research with its retrospective structure, we did not apply to ethics committee approval and an extra formal consent other than the patients had given prior to hospitalization was waived. This situation complies with the principles outlined in the Helsinki Declaration of 1975, as revised in 2008. All authors had full access to the data in the study and take responsi- The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request. ORCID _ Ibrahim Mungan https://orcid.org/0000-0003-0002-3643 Müçteba Can https://orcid.org/0000-0002-8316-5075 Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries Cellular Pathology as Based upon Physiological and Pathological Histology. Philadelphia Inflammation and cancer: back to Virchow? 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