C-reactive protein-albumin-lymphocyte index is a useful indicator for recurrence and survival following curative resection of stage I–III colorectal cancer

C-reactive protein-albumin-lymphocyte index is a useful indicator for recurrence and survival following curative resection of stage I–III colorectal cancer | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article C-reactive protein-albumin-lymphocyte index is a useful indicator for recurrence and survival following curative resection of stage I–III colorectal cancer Tomoaki Bekki, Manabu Shimomura, Takuya Yano, Saki Sato, Atsuhiro Watanabe, and 8 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4221754/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Purpose Recently, several simple inflammation-based prognostic scores that can be calculated easily from serum parameters, have been reported to be related to colorectal cancer prognosis. This study aimed to investigate factors influencing the prognosis of patients, including inflammation-based prognostic scores, with stage I–III colorectal cancer following curative resection. Methods This single-center study included 608 patients with stage I–III colorectal cancer who underwent curative resection between April 2010 and December 2018. A retrospective analysis was performed to identify the prognosis-associated variables in these patients. Next, 1659 patients with stage I–III colorectal cancer who underwent curative resection from a multi-center database belonging to the Hiroshima Surgical study group of Clinical Oncology were analyzed for survival. Results Of the inflammation-based prognostic scores, only preoperative C-reactive protein-albumin-lymphocyte index was revealed to predict a poor prognosis in patients with stage I–III colorectal cancer following curative resection. The low C-reactive protein-albumin-lymphocyte index was associated with poor overall survival and recurrence-free survival, which was similar in patients from multi-center database. The C-reactive protein-albumin-lymphocyte index was found to be associated with patient age, systemic condition, comorbidities, and tumor factors. The time-dependent area under the curve for the C-reactive protein-albumin-lymphocyte index was superior to those of other inflammation-based prognostic scores in most postoperative observation periods. Conclusions The preoperative C-reactive protein-albumin-lymphocyte index was independently associated with long-term prognosis in patients with stage I–III colorectal cancer following curative resection. colorectal cancer curative resection C-reactive protein-albumin-lymphocyte index inflammation-based prognostic scores Figures Figure 1 Figure 2 Figure 3 Figure 4 Introduction Colorectal disease (CRC) is the most frequently diagnosed gastrointestinal cancer and the second most common new cause of cancer-related deaths worldwide [ 1 ]. It accounts for approximately 10% of new cancer cases and cancer-related deaths worldwide [ 1 ]. The frequency at which CRC is encountered in clinical practice is increasing; it is critical to identify prognostic markers easily and to plan appropriate treatment strategies for CRC. It has been reported that systemic inflammatory responses play a central role in carcinogenesis and cancer progression [ 2 ]. According to epidemiological studies, various types of cancers show predisposition to the development of chronic inflammation [ 3 ], and inflammation responses influence prognosis by providing a suitable environment for tumor progression [ 4 ]. C-reactive protein (CRP) is a common clinical indicator that reflects the inflammatory levels in patients [ 5 ]. Hypoalbuminemia is associated with inflammation [ 6 ]; albumin (Alb) is not an indicator of the nutritional condition of patients but rather an indicator of their recovery from inflammation [ 7 ]. Host immune function is also recognized as a pivotal factor influencing both carcinogenesis and progression of cancer; lymphocyte count is an indicator which reflects immune function of patients [ 8 ]. In patients with cancer, Alb values and lymphocyte counts are reduced, and CRP values are elevated owing to inflammation, poor nutrition, and a weakened immune system. Based on this principle, several simple indicators such as C-reactive protein/albumin ratio (CAR), prognostic nutritional index (PNI), and modified Glasgow prognostic score (mGPS), calculated from serum parameters, including lymphocytes, Alb, and CRP, have been reported to be related to CRC prognosis [ 9 , 10 ]. Recently, the C-reactive protein-albumin-lymphocyte (CALLY) index which is calculated from CRP, Alb, and lymphocyte counts drawn from blood examination results, was reported as a new inflammation-based prognostic scores (IBPS) [ 11 ]. As it is calculated from inflammatory responses and factors indicative of immune function, it is being increasingly reported as a prognostic indicator for various types of carcinomas [ 11 – 14 ]. However, a few studies have reported the effect of CALLY index on the prognosis of patients with CRC [ 15 ]. To date, there have been no studies detailing the prognostic impact of the CALLY index following curative resection for stage I-III CRC. This retrospective study investigated prognostic factors, including preoperative IBPS such as CALLY index, PNI, and mGPS, which affect the prognosis of patients who underwent curative resection for stage I–III CRC. Materials and Methods Study Population This retrospective study evaluated 663 patients with stage I–III CRC who underwent R0 resection between April 2010 and December 2018 at the Hiroshima University Hospital. Patients with other primary malignancies during the same period, heterochronic CRC within 5 years, or coexisting colon and rectal cancers were excluded. Finally, 608 patients who underwent R0 resection were enrolled in this single-center study. For the multi-center study, 1804 patients with stage I–III CRC who underwent R0 resection for the first time between January 2017 and December 2018 at 14 institutions, excluding Hiroshima University Hospital, which belongs to the Hiroshima Surgical study group of Clinical Oncology (HiSCO) were evaluated, and we analyzed 1659 patients, excluding 145 patients because of the exclusion criteria described above. Survival time analysis was performed as a multi-center study to confirm the results of the single-center study. This study was conducted in accordance with the guidelines of the Declaration of Helsinki (Fortaleza, Brazil, October 2013) and was approved by the Institutional Review Board of Hiroshima University Hospital (approval no. E-744-4, E-2570). Definition of inflammation-based prognostic scores IBPS were calculated using preoperative blood examinations at initial visit. The CALLY index was calculated as serum Alb level (g/dL) multiplied by the peripheral lymphocyte count and divided by serum CRP level (mg/dL) multiplied by 10000 [(Alb × lymphocyte) ÷ (CRP × 10 4 )][ 11 ]. The neutrophil/lymphocyte ratio (NLR) was calculated as a ratio: neutrophil (%)/relative lymphocyte (%).The PNI was calculated as 10 × Alb level (g/dL) + 0.005 × total lymphocyte count (per mm 3 ) [ 16 ]. The mGPS was calculated as previously described [ 17 ]. Patients with both an increased CRP level (> 1.0 mg/dL) and hypoalbuminemia (< 3.5 g/dL) were allocated a score of 2. Patients showing one or neither of these blood chemistry abnormalities were allocated a score of 1 or 0, respectively. Treatment and follow-up Follow-up blood examinations to identify tumor markers were performed every 3–6 months, 5 years after surgery. Simple or enhanced abdominal computed tomography was performed to rule out recurrence every 6–12 months, and colonoscopy was performed in the first, third, and fifth years after surgery. Patients with high-risk stage II or III CRC underwent postoperative adjuvant chemotherapy (ACT). Postoperative ACT for older patients or those with severe comorbidities was performed at the discretion of the primary surgeon based on the patients’ general condition. Statistical analysis Continuous variables are presented as medians and interquartile ranges. Nominal variables are expressed as numbers (%). Nonparametric quantitative data were analyzed using the Mann–Whitney U -test. The chi-square test or Fisher’s exact test was performed to determine the relationships among nominal variables. For continuous variables such as operative time and intraoperative blood loss, median values were used as cutoff values. The cutoff values for IBPS were set using receiver operating characteristic (ROC) curve analysis with reference to overall survival (OS) after surgery. The performance of the prognostic systems was evaluated in terms of the area under the ROC (AUROC) curve. The AUROC was compared between each model using DeLong’s method. The Kaplan–Meier method was used to analyze OS and recurrence-free survival (RFS), and the log-rank test was used to compare parameters between different groups. Multivariate analyses were performed to assess the factors influencing OS and RFS using the Cox regression model. All variables were included in the multivariate models, and the backward elimination method with a removal criterion of P = 0.10 was used to select the covariates. The prognostic capabilities of the CALLY index, PNI, NLR, and mGPS were compared using time-dependent ROC curves and the area under the curve (AUC). Harrell’s concordance index (C-index) was calculated for each model to determine which index had a predictive association with the endpoints. Bootstrapping method was used to calculate 95% confidence intervals (CI). P-values < 0.05 were considered statistically significant. Calculations were performed using JMP v17 (SAS Institute, Cary, NC, USA) and EZR Ver 1.61 (Saitama Medical Center, Jichi Medical University, Saitama, Japan) [ 18 ]. Results Characteristics of patients with CRC in single-center study Among 663 patients who underwent R0 curative resection of stage I–III CRC between April 2010 and December 2018 at our institute, 608 patients were enrolled in single-center study, excluding 55 patients because of the exclusion criteria. Table 1 summarizes the characteristics of the patients in single-institution study. The median age of the patients was 67 years, with more men than women among the patients enrolled. The median CEA and CA19-9 were 2.9 ng/mL and 6.0 U/mL, respectively. Overall, 87 patients (14.3%) experienced recurrence. Figure 1 presents a comparison of ROC curve analysis for each IBPS with reference to OS after surgery. The AUC value of the CALLY index was 0.6549, which was higher than that of the other indices (PNI, 0.5982; NLR, 0.5694; mGPS, 0.5954). Table 1 Patient characteristics in single-center study Characteristics Patients (n = 608) Male/Female 371/237 Age (years) 67 (61–75) BMI (kg/m 2 ) 22.6 (20.4–24.6) ASA-PS ≥ 3 33 (5.4%) HTN (+) 231 (38.0%) DM (+) 124 (20.4%) DL (+) 186 (30.6%) Ventilatory disease (+) 47 (7.7%) Medication: antiplatelet or coagulation agent 74 (12.2%) CEA (ng/mL) 2.9 (1.8–5.6) CA19-9 (U/mL) 6.0 (3.0–13.0) PNI 51.4 (47.1–54.7) CALLY index 8.4 (2.5–19.8) NLR 2.3 (1.7–3.2) mGPS 0/1/2 495/87/26 Tumor localization: colon/rectum 335/273 pT ≥ 4 32 (5.3%) pN (+) 177 (19.1%) Histology: other than differentiated carcinoma 76 (12.6%) Vascular invasion (+) 385 (63.5%) Continuous variables are expressed as medians (interquartile ranges). Qualitative variables are expressed as numbers (%). Abbreviations: BMI, body mass index; ASA-PS, American Society of Anesthesiologists Physical Status; HTN, hypertension; DM, diabetes mellitus; DL, dyslipidemia; CEA, carcinoembryonic antigen; CA19-9, carbohydrate antigen 19 − 9; PNI, prognostic nutrition index; CALLY index, C-reactive protein-albumin-lymphocyte index; NLR, neutrophile/lymphocyte ratio; mGPS, modified Glasgow prognostic score. Comparison of univariate and multivariate analyses of prognostic factors for OS and RFS in patients with stage I-III CRC in single-center study Table 2 summarizes the results of univariate and multivariate analyses of prognostic factors for OS in a single-center study. In the univariate analysis, statistically significant prognostic factors for poor OS were age ≥ 75 (year) ( P = 0.0074), American society of Anesthesiologists Physical Status (ASA-PS) ≥ 3 ( P = 0.0049), diabetes mellitus (DM) ( P = 0.0102), carcinoembryonic antigen (CEA) > 5 (ng/mL) ( P 37 (U/mL) ( P < 0.0001), PNI ≤ 46 ( P = 0.0054), CALLY index ≤ 3.35 ( P 3.0 ( P = 0.0063), mGPS ≥ 1 ( P = 0.0014), open surgery ( P = 0.0256), intraoperative blood transfusion ( P = 0.0023), pT ≥ 4 ( P = 0.0419), pathological positivity of lymph node metastasis ( P < 0.0001), and positivity of vascular invasion ( P = 0.0251). In the multivariate analysis, the following six factors were identified as prognostic factors for poor OS in patients: age ≥ 75 (year) (hazard ratio [HR] = 2.154; 95% CI = 1.21–3.82, P = 0.0087), ASA-PS ≥ 3 (HR = 2.816; 95% CI = 1.13–6.99, P = 0.0256), CEA > 5 (ng/mL) (HR = 1.938; 95% CI = 1.09–3.44, P = 0.0241), CA19-9 > 37 (U/mL) (HR = 3.126; 95% CI = 1.50–6.49, P = 0.0022), CALLY index ≤ 3.35 (HR = 2.069; 95% CI = 1.20–3.57, P = 0.0091), and pathological positivity of lymph node metastasis (HR = 3.108; 95% CI = 1.80–5.36, P < 0.0001). Table 2 Univariate and multivariate analyses of prognostic factor for overall survival in single-center study Variables Univariate Multivariate N = 608 HR 95% CI P -value HR 95% CI P -value Male 371 1.221 0.70–2.12 0.4775 1.725 0.97–3.08 0.0658 Age (year) ≥ 75 153 2.138 1.23–3.73 0.0074 2.154 1.21–3.82 0.0087 BMI (kg/m 2 ) < 25 131 1.764 0.83–3.73 0.1367 ASA-PS ≥ 3 33 3.397 1.45–7.96 0.0049 2.816 1.13–6.99 0.0256 HTN (+) 231 1.398 0.82–2.37 0.2139 DM (+) 124 2.063 1.19–3.58 0.0102 DL (+) 186 1.057 0.61–1.84 0.8440 Ventilatory disease (+) 47 1.253 0.50–3.14 0.6310 Medications: antiplatelet or coagulation agents 74 1.525 0.75–3.11 0.2461 CEA (ng/mL) > 5 165 3.133 1.86–5.28 37 38 5.083 2.68–9.65 < 0.0001 3.126 1.50–6.49 0.0022 PNI ≤ 46 113 2.213 1.27–3.87 0.0054 CALLY index ≤ 3.35 177 2.909 1.73–4.90 3.0 177 2.070 1.23–3.49 0.0063 mGPS ≥ 1 113 2.440 1.41–4.21 0.0014 Open surgery 108 1.932 1.08–3.44 0.0256 Operative time (min) ≥ 280 297 1.500 0.87–2.57 0.1406 Blood loss (mL) ≥ 60 309 1.447 0.85–2.48 0.1774 Intraoperative blood transfusion (+) 25 3.737 1.60–8.73 0.0023 Tumor localization: Rectum 273 1.350 0.80–2.27 0.2576 pT ≥ 4 32 2.488 1.03–5.08 0.0419 pN (+) 177 3.051 1.80–5.18 < 0.0001 3.108 1.80–5.36 < 0.0001 Histology: other than differentiated carcinoma 76 1.527 0.77–3.03 0.2258 Vascular invasion (+) 385 2.194 1.10–4.36 0.0251 Postoperative chemotherapy (+) 197 1.167 0.69–1.99 0.5699 Postoperative complications CD ≥ 3 (+) 45 1.672 0.76–3.70 0.2041 The variables in bold are statistically significant ( P < 0.05). Abbreviations: HR, hazard ratio; CI, confidence interval; BMI, body mass index; ASA-PS, American Society of Anesthesiologists Physical Status; HTN, hypertension; DM, diabetes mellitus; DL, dyslipidemia; CEA, carcinoembryonic antigen; CA19-9, carbohydrate antigen 19 − 9; PNI, prognostic nutrition index; CALLY index, C-reactive protein-albumin-lymphocyte index; NLR, neutrophil/lymphocyte ratio; mGPS, modified Glasgow prognostic score; CD, Clavien-Dindo. Table 3 summarizes the results of univariate and multivariate analyses of prognostic factors for RFS in a single-center study. In the univariate analysis, statistically significant prognostic factors for poor RFS were as follows: male ( P = 0.0202), ASA-PS ≥ 3 ( P = 0.0043), DM ( P = 0.0266), CEA > 5 (ng/mL) ( P 37 (U/mL) ( P = 0.0001), PNI ≤ 46 ( P = 0.0116), CALLY index ≤ 3.35 ( P = 0.0022), NLR > 3.0 ( P = 0.0076), mGPS ≥ 1 ( P = 0.0005), open surgery ( P = 0.0109), operative time ≥ 280 (min) ( P = 0.0014), blood loss ≥ 60 (mL) ( P = 0.0029), rectal cancer ( P = 0.0006), pT ≥ 4 ( P = 0.0021), pathological positivity of lymph node metastasis ( P < 0.0001), positivity of vascular invasion ( P = 0.0006), and postoperative chemotherapy ( P = 0.0039). In the multivariate analysis, the following seven factors were identified as prognostic factors for poor RFS: male (HR = 1.789; 95% CI = 1.17–2.72, P = 0.0068), ASA-PS ≥ 3 (HR = 2.599; 95% CI = 1.32–5.12, P = 0.0058), CEA > 5 (ng/mL) (HR = 2.136; 95% CI = 1.44–3.17, P = 0.0002), CA19-9 > 37 (U/mL) (HR = 2.006; 95% CI = 1.13–3.57, P = 0.0177), CALLY index ≤ 3.35 (HR = 1.556; 95% CI = 1.05–2.31, P = 0.0289), rectal cancer (HR = 1.891; 95% CI = 1.28–2.79, P = 0.0013), and pathological positivity of lymph node metastasis (HR = 2.796; 95% CI = 1.91–4.09, P < 0.0001). Figures 2 summarizes the Kaplan–Meier analysis showing OS and RFS in a single-center study using the CALLY index. The low CALLY index was associated with poor OS and RFS (OS: P < 0.0001; log-rank test; Fig. 2 a, RFS: P = 0.0019; log-rank test; Fig. 2 b). Table 3 Univariate and multivariate analyses of prognostic factor for recurrence-free survival in single-center study Variables Univariate Multivariate N = 608 HR 95% CI P -value HR 95% CI P -value Male 371 1.627 1.08–2.45 0.0202 1.789 1.17–2.72 0.0068 Age (year) ≥ 75 153 0.987 0.63–1.54 0.9531 BMI (kg/m 2 ) < 25 131 1.536 0.93–2.54 0.0956 ASA-PS ≥ 3 33 2.578 1.34–4.94 0.0043 2.599 1.32–5.12 0.0058 HTN (+) 231 1.122 0.76–1.65 0.5556 DM (+) 124 1.600 1.06–2.42 0.0266 DL (+) 186 1.131 0.76–1.68 0.5398 Ventilatory disease (+) 47 1.057 0.53–2.09 0.8731 Medications: antiplatelet or coagulation agents 74 0.9323 0.52–1.67 0.8128 CEA (ng/mL) > 5 165 2.873 1.98–4.17 37 38 2.915 1.69–5.03 0.0001 2.006 1.13–3.57 0.0177 PNI ≤ 46 113 1.728 1.13–2.64 0.0116 CALLY index ≤ 3.35 177 1.812 1.24–2.65 0.0022 1.556 1.05–2.31 0.0289 NLR > 3.0 177 1.681 1.15–2.46 0.0076 mGPS ≥ 1 113 2.070 1.38–3.11 0.0005 Open surgery 108 1.745 1.14–2.68 0.0109 Operative time (min) ≥ 280 297 1.894 1.28–2.81 0.0014 Blood loss (mL) ≥ 60 309 1.801 1.22–2.65 0.0029 Intraoperative Blood transfusion (+) 25 2.024 0.94–4.36 0.0717 Tumor localization: Rectum 273 1.943 1.33–2.85 0.0006 1.891 1.28–2.79 0.0013 pT ≥ 4 32 2.577 1.41–4.71 0.0021 pN (+) 177 2.701 1.86–3.92 < 0.0001 2.796 1.91–4.09 < 0.0001 Histology: other than differentiated carcinoma 76 1.061 0.60–1.86 0.8364 Vascular invasion (+) 385 2.276 1.43–3.63 0.0006 Postoperative chemotherapy (+) 197 1.736 1.19–2.53 0.0039 Postoperative complications CD ≥ 3 (+) 45 1.413 0.76–2.64 0.2768 The variables in bold are statistically significant ( P < 0.05). Abbreviations: HR, hazard ratio; CI, confidence interval; BMI, body mass index; ASA-PS, American Society of Anesthesiologists Physical Status; HTN, hypertension; DM, diabetes mellitus; DL, dyslipidemia; CEA, carcinoembryonic antigen; CA19-9, carbohydrate antigen 19 − 9; PNI, prognostic nutrition index; CALLY index, C-reactive protein-albumin-lymphocyte index; NLR, neutrophil/lymphocyte ratio; mGPS, modified Glasgow prognostic score; CD, Clavien-Dindo. Comparison of backgrounds by preoperative CALLY index in single-center study Table 4 summarizes the characteristics of the patients in the high and low CALLY index groups in this single-center study. Compared with the low-CALLY index group, the high-CALLY index group included younger patients ( P = 0.0004), higher body mass index ( P = 0.0160), less patients with ASA-PS ≥ 3 ( P < 0.0001), less patients with DM ( P = 0.0486), less patients with ventilatory disease ( P = 0.0347), less patients who underwent open surgery ( P < 0.0001), and less patients with intraoperative blood transfusion ( P < 0.0001). Intraoperative blood loss ( P < 0.0001) and the number of patients with deeper tumor invasion ( P < 0.0001) were higher in the low-CALLY-index group than in the high-CALLY index group. Tumor marker levels were higher in the low-CALLY index group than in the high-CALLY index group (CEA: P < 0.0001, CA19-9: P = 0.0009). Among the IBPS, the PNI ( P < 0.0001), NLR ( P < 0.0001), and mGPS ( P < 0.0001) were significantly different between the two groups. Table 4 Comparison of patient characteristics with high- and low-CALLY index group in single-center study High-CALLY index group (n = 431) Low-CALLY index group (n = 177) P -value Age (year) 66 (60–73) 69 (63–78) 0.0004 Sex (M/F) 259/172 112/65 0.4646 BMI (kg/m 2 ) 22.8 (20.6–24.7) 21.9 (19.7–24.3) 0.0160 ASA-PS ≥ 3 12 (2.8%) 21 (11.9%) < 0.0001 HTN (+) 157 (36.4%) 74 (41.8%) 0.2143 DM (+) 79 (18.3%) 45 (25.4%) 0.0486 DL (+) 137 (31.8%) 49 (27.7%) 0.3186 Ventilatory disease (+) 27 (6.3%) 20 (11.3%) 0.0347 Medication: antiplatelet or coagulation agent 49 (11.4%) 25 (14.1%) 0.3452 Lymphocyte count (/µL) 1668 (1336–2098) 1410 (1008–1913) < 0.0001 Alb (g/dL) 4.4 (4.1–4.6) 3.9 (3.5–4.2) < 0.0001 CRP (mg/dL) 0.05 (0.02–0.10) 0.56 (0.29–1.09) < 0.0001 CEA (ng/mL) 2.6 (1.6–4.9) 3.5 (2.3–7.9) < 0.0001 CA19-9 (U/mL) 6.0 (3.0–11.0) 8.0 (3.0–19.3) 0.0009 PNI 52.5 (49.3–55.8) 46.3 (40.7–51.0) < 0.0001 NLR 2.1 (1.5–2.8) 3.1 (2.1–4.5) < 0.0001 mGPS 426/5/0 69/82/26 < 0.0001 Open/Laparoscopic or robot-assisted 51/380 57/120 < 0.0001 Operative time (min) 284 (237–356) 275 (223–352) 0.5538 Blood loss (ml) 50 (26–123) 81 (35–279) < 0.0001 Intraoperative blood transfusion (+) 9 (2.1%) 16 (9.1%) < 0.0001 Tumor localization: colon/rectum 228/203 107/70 0.0890 pT (1/2/3/4) 155/95/167/14 37/25/97/18 < 0.0001 pN (+) 124 (28.8%) 53 (29.9%) 0.7724 Histology: other than differentiated carcinoma 47 (11.0%) 29 (16.4%) 0.0681 Vascular invasion (+) 267 (62.1%) 118 (67.1%) 0.2502 Postoperative chemotherapy (+) 143 (33.2%) 54 (30.5%) 0.5228 Postoperative complications CD ≥ 3 (+) 31 (7.2%) 14 (7.9%) 0.7570 The variables in bold are statistically significant (P < 0.05). Continuous variables are expressed as medians (interquartile ranges). Qualitative variables are expressed as numbers (%). Abbreviations: M, male; F, female; BMI, body mass index; ASA-PS, American Society of Anesthesiologists Physical Status; HTN, hypertension; DM, diabetes mellitus; DL, dyslipidemia; Alb, albumin; CRP, C-reactive protein; CEA, carcinoembryonic antigen; CA19-9, carbohydrate antigen 19 − 9; PNI, prognostic nutrition index; NLR, neutrophile/lymphocyte ratio; mGPS, modified Glasgow prognostic score; CD, Clavien-Dindo. Comparison of inflammation-based prognostic scores for OS and RFS in single-center study Figure 3 summarizes the comparison of time-dependent ROC curve of IBPS for OS and RFS in single-center study. A time-dependent ROC curve was used to calculate the AUC values at different time points. In terms of both OS and RFS, Harrell’s concordance index (C-index) values for the CALLY index were superior than those for other IBPS after surgery (OS: CALLY index, 0.655; 95% CI = 0.571–0.739, SE = 0.043; PNI, 0.616; 95% CI = 0.522–0.803, SE = 0.046; NLR, 0.574; 95% CI = 0.487–0.663, SE = 0.046; mGPS, 0.593; 95% CI = 0.520–0.665, SE = 0.037; Fig. 3 a, RFS: CALLY index, 0.598; 95% CI = 0.542–0.656, SE = 0.030; PNI, 0.580; 95% CI = 0.521–0.637, SE = 0.030; NLR, 0.586; 95% CI = 0.530–0.641, SE = 0.023; mGPS, 0.564; 95% CI = 0.520–0.612, SE = 0.023; Fig. 3 b). External multi-center analysis of the CALLY index associated with prognosis of stage I-III CRC following curative resection To confirm the applicability of the cut-off value of the CALLY index, which was identified as a prognostic factor following curative resection for CRC based on our institutional study, we conducted a survival time analysis using the HiSCO multi-center dataset, which included a larger population. Figure 4 summarizes the Kaplan–Meier analysis showing OS and RFS in a multi-center study using the CALLY index with a cutoff value determined in a single-center study. A low CALLY index was associated with poor OS and RFS (OS: P < 0.0001, log-rank test; Fig. 4 a; RFS: P < 0.0001, log-rank test; Fig. 4 b). Supplemental Table 1 summarizes the characteristics of the patients in the high- and low-CALLY index groups in the multi-center study. Compared with the low-CALLY index group, the high-CALLY index group included younger patients ( P < 0.0001), less patients with ASA-PS ≥ 3 ( P < 0.0001). The number of patients with deeper tumor invasion ( P < 0.0001) were higher in the low-CALLY-index group than in the high-CALLY index group. Tumor marker levels were higher in the low CALLY index group than in the high CALLY index group (CEA, P < 0.0001; CA19-9, P = 0.0002). The above results of the multi-center study were similar to those of the single-center study. Discussion This retrospective study investigated prognostic factors, which include IBPS, affecting long-term prognosis in patients who underwent curative resection for stage I–III CRC. In addition to severe systemic condition and tumor factors such as tumor markers and lymph node metastasis, preoperative low CALLY index, an inflammation-based marker, was associated with poor long-term prognosis in patients with stage I–III CRC following curative resection. CRC is the most frequently diagnosed gastrointestinal cancer. It ranks third in both incidence and mortality in males, and second in incidence and third in mortality in females worldwide [ 1 ]. Various factors such as age, postoperative complication, tumor-node-metastasis (TNM) stage, tumor marker, tumor differentiation, and circulating tumor cells, have been reported as prognostic factors affecting the postoperative outcome of stage I–III CRC [ 19 – 21 ]. In this study, age, male, severe systemic condition, comorbidities, and tumor factors were identified as factors affecting postoperative prognosis of CRC, which was consistent with the results of previous studies. Interestingly, among the IBPS compared in this study, only the CALLY index was identified as a useful postoperative prognostic indicator following curative resection for CRC. The CALLY index, which is calculated from CRP and Alb reflecting inflammation, and lymphocyte counts reflecting immune function, was reported as an IBPS, and as a postoperative prognostic predictor for hepatocellular carcinoma [ 11 ]. The CALLY index is being increasingly reported as being associated with prognosis for various types of carcinomas [ 11 – 14 ]. In this study, compared to other IBPS, the CALLY index was an accurate prognostic indicator, and a low CALLY index was an independent poor prognostic factor for stage I–III CRC after curative resection. Both single- and multi-center studies have shown that a low CALLY index is associated with poor postoperative prognosis in patients with CRC and is strongly related to age and tumor factors. In addition, the preoperative CALLY index was found to be a better predictor of prognosis than the other markers in a time-dependent ROC curve for OS and RFS in single-center study. This index reflects inflammation and may be a sensitive indicator of preoperative systemic status, and it can be considered useful in predicting postoperative outcomes for patients with various types of cancers. Cancer development and progression have been shown to be closely associated with the host nutritional status and inflammatory responses within the tumor microenvironment [ 2 , 22 , 23 ]; high CRP and low Alb levels were reported as factors for poor survival in patients with CRC [ 24 , 25 ]. Peripheral lymphocyte count has also been reported as a prognostic indicator of patients with CRC [ 26 ]. In patients with cancer, Alb values and lymphocyte counts are reduced, and the CRP values are elevated owing to inflammation, poor nutrition, and a weakened immune system; various IBPS calculated from CRP and Alb which are called inflammatory markers, and lymphocyte, which is a surrogate marker of immunocompetence, were already reported as prognostic indicators for CRC following curative resection [ 9 , 10 , 27 ]. Because the CALLY index is calculated from three factors mentioned above, it more accurately reflects the inflammatory responses within the tumor microenvironment and may be a more sensitive marker for the prognosis of various cancers than other IBPS. In fact, this study revealed that the CALLY index is associated with tumor markers and tumor depth, and it was found to be the most sensitive prognostic indicator for patients with stage I–III CRC following curative resection among the IBPS examined in this study. The CALLY index is considered as an extremely useful marker to identify the patients at risk of poor prognosis and to establish appropriate treatment strategies. In addition, another reason why the CALLY index is considered a valuable prognostic indicator for patients with stage I–III CRC following curative resection is its susceptibility to the influence of age. The prevalence of cancer in older patients is increasing, and by 2030, approximately 70% of all new cancer cases will be diagnosed in individuals aged ≥ 65 years [ 28 ]. In this study, it was confirmed that age, a known prognostic factor for postoperative CRC, is associated with the CALLY index. Generally, older patients have age-related declines in organ function and immunity [ 29 ], and a relation between aging and decreased lymphocyte counts has been reported [ 30 ]. Recently, frailty has also been reported as a poor prognostic factor for stage I–III CRC following curative resection [ 31 ]; elevated CRP and hypoalbuminemia, which lead to chronic inflammation in older patients, have been suggested as candidate indicators for frailty [ 32 ]. In other words, the three factors mentioned above, which are components of the CALLY index, are also considered to be affected by not only tumor factors but also aging. Based on the above, the CALLY index, which is influenced by age, may be considered as an accurate prognostic indicator after surgery for various types of cancers, including CRC. This study has several limitations. First, its retrospective design. Second, all common postoperative prognostic factors for CRC reported in previous studies were not included in the analysis. Third, the cohorts for biological markers such as RAS, BRAF, and MSI had a limited sample size and could not be included in the analysis. Therefore, more analyses are needed to confirm whether these results are similar to those of the present study after accumulating more cases of these biological markers. However, the results of this study, including single- and multi-center analyses, show that the CALLY index is a good prognostic indicator for patients with CRC following curative resection. Conclusions Low preoperative CALLY index was found to be independently associated with poor prognosis in patients with stage I–III CRC after curative resection. Preoperative CALLY index was a useful assessment index for predicting the prognosis of patients who underwent curative resection of stage I–III CRC. Further studies investigating the association between CALLY index and CRC prognosis are warranted. Declarations Data availability The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request. Funding This study did not receive any specific grants from funding agencies in the public, commercial, or non-profit sectors. Competing interests The authors have no relevant financial or non-financial interests to disclose. Author contributions: TB, TY, SA and MS drafted the manuscript. MH contributed to the interpretation of data and analysis. HO substantively revised the manuscript. All the authors have cooperated in the accumulation of cases and approved the final manuscript. Ethics statements There is no need for consent to participate to be obtained due to retrospective study. Administrative permissions were not required to access and use the medical records described in this study. This study was authorized in advance by the institutional review board of the Hiroshima University Hospital (approval number: E-744-4, E-2527). Acknowledgments We thank all the members of the Hiroshima Surgical study group of Clinical Oncology. We would like to thank Editage (www.editage.com ) for the English language editing. References Sung H, Ferlay J, Siegel RL et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021; 71: 209–249. Mantovani A, Allavena P, Sica A, Balkwill F. Cancer-related inflammation. Nature 2008; 454: 436–444. Balkwill F, Mantovani A. Inflammation and cancer: back to Virchow? Lancet. 2001; 357: 539–545. Diakos CI, Charles KA, McMillan DC, Clarke SJ. Cancer-related inflammation and treatment effectiveness. Lancet Oncol. 2014; 15: e493-503. Sproston NR, Ashworth JJ. Role of C-Reactive Protein at Sites of Inflammation and Infection. Front Immunol. 2018; 9: 754. Soeters PB, Wolfe RR, Shenkin A. Hypoalbuminemia: Pathogenesis and Clinical Significance. JPEN J Parenter Enter Nutr. 2019; 43: 181–193. Fuhrman MP, Charney P, Mueller CM. Hepatic proteins and nutrition assessment. J Am Diet Assoc. 2004; 104: 1258–1264. doi: 10.1016/j.jada.2004.05.213 . Fleisher TA, Oliveira JB. Functional and molecular evaluation of lymphocytes. J Allergy Clin Immunol. 2004; 114: 227–234; quiz 235. Ishizuka M, Nagata H, Takagi K et al. Clinical Significance of the C-Reactive Protein to Albumin Ratio for Survival After Surgery for Colorectal Cancer. Ann Surg Oncol. 2016; 23: 900–907. Xie H, Wei L, Yuan G et al. Prognostic Value of Prognostic Nutritional Index in Patients With Colorectal Cancer Undergoing Surgical Treatment. Front Nutr. 2022; 9: 794489. Iida H, Tani M, Komeda K et al. Superiority of CRP-albumin-lymphocyte index (CALLY index) as a non-invasive prognostic biomarker after hepatectomy for hepatocellular carcinoma. HPB (Oxford). 2022; 24: 101–115. Zhang H, Shi J, Xie H et al. Superiority of CRP-albumin-lymphocyte index as a prognostic biomarker for patients with gastric cancer. Nutrition. 2023; 116: 112191. Tsunematsu M, Haruki K, Taniai T et al. The impact of C-reactive protein-albumin-lymphocyte (CALLY) index on the prognosis of patients with distal cholangiocarcinoma following pancreaticoduodenectomy. Ann Gastroenterol Surg. 2023; 7: 503–511. Liu XY, Zhang X, Zhang Q et al. The value of CRP-albumin-lymphocyte index (CALLY index) as a prognostic biomarker in patients with non-small cell lung cancer. Support Care Cancer. 2023; 31: 533. Yang M, Lin SQ, Liu XY et al. Association between C-reactive protein-albumin-lymphocyte (CALLY) index and overall survival in patients with colorectal cancer: From the investigation on nutrition status and clinical outcome of common cancers study. Front Immunol. 2023; 14: 1131496. Onodera T, Goseki N, Kosaki G. [Prognostic nutritional index in gastrointestinal surgery of malnourished cancer patients]. Nihon Geka Gakkai zasshi. 1984; 85: 1001–1005. O'Gorman P, McMillan DC, McArdle CS. Prognostic factors in advanced gastrointestinal cancer patients with weight loss. Nutr Cancer 2000; 37: 36–40. Kanda Y. Investigation of the freely available easy-to-use software ‘EZR’ for medical statistics. Bone Marrow Transplant. 2013;48:452–458. Uen YH, Lu CY, Tsai HL et al. Persistent presence of postoperative circulating tumor cells is a poor prognostic factor for patients with stage I-III colorectal cancer after curative resection. Ann Surg Oncol 2008; 15: 2120–2128. Mehrkhani F, Nasiri S, Donboli K et al. Prognostic factors in survival of colorectal cancer patients after surgery. Colorectal Dis. 2009; 11: 157–161. Miyamoto Y, Hiyoshi Y, Tokunaga R et al. Postoperative complications are associated with poor survival outcome after curative resection for colorectal cancer: A propensity-score analysis. J Surg Oncol. 2020; 122: 344–349. Michels KB. The role of nutrition in cancer development and prevention. Int J Cancer. 2005; 114: 163–165. Taniguchi K, Karin M. NF-κB, inflammation, immunity and cancer: coming of age. Nat Rev Immunol. 2018; 18: 309–324. Lai CC, You JF, Yeh CY et al. Low preoperative serum albumin in colon cancer: a risk factor for poor outcome. Int J Colorectal Dis. 2011; 26: 473–481. Swede H, Hajduk AM, Sharma J et al. Baseline serum C-reactive protein and death from colorectal cancer in the NHANES III cohort. Int J Cancer. 2014; 134: 1862–1870. Iseki Y, Shibutani M, Maeda K et al. The impact of the preoperative peripheral lymphocyte count and lymphocyte percentage in patients with colorectal cancer. Surg Today. 2017; 47: 743–754. Guthrie GJ, Roxburgh CS, Farhan-Alanie OM et al. Comparison of the prognostic value of longitudinal measurements of systemic inflammation in patients undergoing curative resection of colorectal cancer. Br J Cancer. 2013; 109: 24–28. Smith BD, Smith GL, Hurria A et al. Future of cancer incidence in the United States: burdens upon an aging, changing nation. J Clinl Oncol. 2009; 27: 2758–2765. Nikolich-Žugich J. The twilight of immunity: emerging concepts in aging of the immune system. Nat Immunol. 2018; 19: 10–19. Erkeller-Yuksel FM, Deneys V, Yuksel B et al. Age-related changes in human blood lymphocyte subpopulations. J Pediatri. 1992; 120: 216–222. Mima K, Miyanari N, Morito A et al. Frailty is an independent risk factor for recurrence and mortality following curative resection of stage I-III colorectal cancer. Ann Gastroenterol Surg. 2020; 4: 405–412. Velissaris D, Pantzaris N, Koniari I et al. C-Reactive Protein and Frailty in the Elderly: A Literature Review. J Clin Med Res. 2017; 9: 461–465. Additional Declarations No competing interests reported. Supplementary Files Suptable1.docx Supplemental Table 1: Comparison of patient characteristics with high- and low-CALLY index group in multi-center study. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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University","correspondingAuthor":false,"prefix":"","firstName":"Shintaro","middleName":"","lastName":"Akabane","suffix":""},{"id":288204221,"identity":"d6d3e429-d93f-4b1b-9d0a-ed6a2647f304","order_by":12,"name":"Hideki Ohdan","email":"","orcid":"","institution":"Hiroshima University","correspondingAuthor":false,"prefix":"","firstName":"Hideki","middleName":"","lastName":"Ohdan","suffix":""}],"badges":[],"createdAt":"2024-04-05 08:47:28","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4221754/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4221754/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":54445901,"identity":"85e29462-cdaf-4d18-97cb-7f36eff158c4","added_by":"auto","created_at":"2024-04-10 16:19:22","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":38037,"visible":true,"origin":"","legend":"\u003cp\u003eComparison of the areas under receiver operating curves for survival prediction among the IBPS.\u003c/p\u003e","description":"","filename":"20240331Fig1.png","url":"https://assets-eu.researchsquare.com/files/rs-4221754/v1/9ed818f2b58d534b9f1675ad.png"},{"id":54445904,"identity":"0f843872-6b66-4853-b62d-8dc7c0f204fd","added_by":"auto","created_at":"2024-04-10 16:19:22","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":25406,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003e2a, 2b\u003c/strong\u003e: Kaplan–Meier curves for overall survival and recurrence-free survival in patients used to compare the high- and low-CALLY index groups in single-center study.\u003c/p\u003e","description":"","filename":"20240331Fig2.png","url":"https://assets-eu.researchsquare.com/files/rs-4221754/v1/28c07b59d6083b1c4746b7c9.png"},{"id":54445902,"identity":"2951ce98-4948-43a6-adbf-47b240f727b3","added_by":"auto","created_at":"2024-04-10 16:19:22","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":39703,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003e3a, 3b\u003c/strong\u003e: Comparison of the time-dependent areas under receiver operating curves for overall survival and recurrence-free survival between CALLY index and other indices in single-center study.\u003c/p\u003e","description":"","filename":"20240331Fig3.png","url":"https://assets-eu.researchsquare.com/files/rs-4221754/v1/30d2d819f45052a8645ee0c3.png"},{"id":54447023,"identity":"e849e705-7759-4002-9352-dbd6a8330637","added_by":"auto","created_at":"2024-04-10 16:27:22","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":24720,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003e4a, 4b\u003c/strong\u003e: Kaplan–Meier curves for overall survival and recurrence-free survival in patients used to compare the high- and low-CALLY index groups in multi-center study.\u003c/p\u003e","description":"","filename":"20240331Fig4.png","url":"https://assets-eu.researchsquare.com/files/rs-4221754/v1/d9023222485178626fa9bd2b.png"},{"id":56411941,"identity":"9e9d9e02-90d7-40bf-86d8-885dcd65f8a2","added_by":"auto","created_at":"2024-05-13 20:32:05","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1404530,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4221754/v1/800d4751-aef8-476f-870a-cfddf5c431fb.pdf"},{"id":54445905,"identity":"67038e8c-bc33-45ff-bf90-01d35a3217fd","added_by":"auto","created_at":"2024-04-10 16:19:22","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":24650,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eSupplemental Table 1\u003c/strong\u003e: Comparison of patient characteristics with high- and low-CALLY index group in multi-center study.\u003c/p\u003e","description":"","filename":"Suptable1.docx","url":"https://assets-eu.researchsquare.com/files/rs-4221754/v1/5b31601aa38fc0878900048d.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"C-reactive protein-albumin-lymphocyte index is a useful indicator for recurrence and survival following curative resection of stage I–III colorectal cancer","fulltext":[{"header":"Introduction","content":"\u003cp\u003eColorectal disease (CRC) is the most frequently diagnosed gastrointestinal cancer and the second most common new cause of cancer-related deaths worldwide [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. It accounts for approximately 10% of new cancer cases and cancer-related deaths worldwide [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. The frequency at which CRC is encountered in clinical practice is increasing; it is critical to identify prognostic markers easily and to plan appropriate treatment strategies for CRC.\u003c/p\u003e \u003cp\u003eIt has been reported that systemic inflammatory responses play a central role in carcinogenesis and cancer progression [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. According to epidemiological studies, various types of cancers show predisposition to the development of chronic inflammation [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e], and inflammation responses influence prognosis by providing a suitable environment for tumor progression [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. C-reactive protein (CRP) is a common clinical indicator that reflects the inflammatory levels in patients [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Hypoalbuminemia is associated with inflammation [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]; albumin (Alb) is not an indicator of the nutritional condition of patients but rather an indicator of their recovery from inflammation [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Host immune function is also recognized as a pivotal factor influencing both carcinogenesis and progression of cancer; lymphocyte count is an indicator which reflects immune function of patients [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. In patients with cancer, Alb values and lymphocyte counts are reduced, and CRP values are elevated owing to inflammation, poor nutrition, and a weakened immune system. Based on this principle, several simple indicators such as C-reactive protein/albumin ratio (CAR), prognostic nutritional index (PNI), and modified Glasgow prognostic score (mGPS), calculated from serum parameters, including lymphocytes, Alb, and CRP, have been reported to be related to CRC prognosis [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eRecently, the C-reactive protein-albumin-lymphocyte (CALLY) index which is calculated from CRP, Alb, and lymphocyte counts drawn from blood examination results, was reported as a new inflammation-based prognostic scores (IBPS) [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. As it is calculated from inflammatory responses and factors indicative of immune function, it is being increasingly reported as a prognostic indicator for various types of carcinomas [\u003cspan additionalcitationids=\"CR12 CR13\" citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. However, a few studies have reported the effect of CALLY index on the prognosis of patients with CRC [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. To date, there have been no studies detailing the prognostic impact of the CALLY index following curative resection for stage I-III CRC.\u003c/p\u003e \u003cp\u003eThis retrospective study investigated prognostic factors, including preoperative IBPS such as CALLY index, PNI, and mGPS, which affect the prognosis of patients who underwent curative resection for stage I\u0026ndash;III CRC.\u003c/p\u003e"},{"header":"Materials and Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy Population\u003c/h2\u003e \u003cp\u003eThis retrospective study evaluated 663 patients with stage I\u0026ndash;III CRC who underwent R0 resection between April 2010 and December 2018 at the Hiroshima University Hospital. Patients with other primary malignancies during the same period, heterochronic CRC within 5 years, or coexisting colon and rectal cancers were excluded. Finally, 608 patients who underwent R0 resection were enrolled in this single-center study.\u003c/p\u003e \u003cp\u003e For the multi-center study, 1804 patients with stage I\u0026ndash;III CRC who underwent R0 resection for the first time between January 2017 and December 2018 at 14 institutions, excluding Hiroshima University Hospital, which belongs to the Hiroshima Surgical study group of Clinical Oncology (HiSCO) were evaluated, and we analyzed 1659 patients, excluding 145 patients because of the exclusion criteria described above. Survival time analysis was performed as a multi-center study to confirm the results of the single-center study.\u003c/p\u003e \u003cp\u003e This study was conducted in accordance with the guidelines of the Declaration of Helsinki (Fortaleza, Brazil, October 2013) and was approved by the Institutional Review Board of Hiroshima University Hospital (approval no. E-744-4, E-2570).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eDefinition of inflammation-based prognostic scores\u003c/h2\u003e \u003cp\u003eIBPS were calculated using preoperative blood examinations at initial visit. The CALLY index was calculated as serum Alb level (g/dL) multiplied by the peripheral lymphocyte count and divided by serum CRP level (mg/dL) multiplied by 10000 [(Alb \u0026times; lymphocyte) \u0026divide; (CRP \u0026times; 10\u003csup\u003e4\u003c/sup\u003e)][\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. The neutrophil/lymphocyte ratio (NLR) was calculated as a ratio: neutrophil (%)/relative lymphocyte (%).The PNI was calculated as 10 \u0026times; Alb level (g/dL)\u0026thinsp;+\u0026thinsp;0.005 \u0026times; total lymphocyte count (per mm\u003csup\u003e3\u003c/sup\u003e) [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. The mGPS was calculated as previously described [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. Patients with both an increased CRP level (\u0026gt;\u0026thinsp;1.0 mg/dL) and hypoalbuminemia (\u0026lt;\u0026thinsp;3.5 g/dL) were allocated a score of 2. Patients showing one or neither of these blood chemistry abnormalities were allocated a score of 1 or 0, respectively.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eTreatment and follow-up\u003c/h2\u003e \u003cp\u003eFollow-up blood examinations to identify tumor markers were performed every 3\u0026ndash;6 months, 5 years after surgery. Simple or enhanced abdominal computed tomography was performed to rule out recurrence every 6\u0026ndash;12 months, and colonoscopy was performed in the first, third, and fifth years after surgery. Patients with high-risk stage II or III CRC underwent postoperative adjuvant chemotherapy (ACT). Postoperative ACT for older patients or those with severe comorbidities was performed at the discretion of the primary surgeon based on the patients\u0026rsquo; general condition.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eContinuous variables are presented as medians and interquartile ranges. Nominal variables are expressed as numbers (%). Nonparametric quantitative data were analyzed using the Mann\u0026ndash;Whitney \u003cem\u003eU\u003c/em\u003e-test. The chi-square test or Fisher\u0026rsquo;s exact test was performed to determine the relationships among nominal variables. For continuous variables such as operative time and intraoperative blood loss, median values were used as cutoff values. The cutoff values for IBPS were set using receiver operating characteristic (ROC) curve analysis with reference to overall survival (OS) after surgery. The performance of the prognostic systems was evaluated in terms of the area under the ROC (AUROC) curve. The AUROC was compared between each model using DeLong\u0026rsquo;s method. The Kaplan\u0026ndash;Meier method was used to analyze OS and recurrence-free survival (RFS), and the log-rank test was used to compare parameters between different groups. Multivariate analyses were performed to assess the factors influencing OS and RFS using the Cox regression model. All variables were included in the multivariate models, and the backward elimination method with a removal criterion of \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.10 was used to select the covariates.\u003c/p\u003e \u003cp\u003eThe prognostic capabilities of the CALLY index, PNI, NLR, and mGPS were compared using time-dependent ROC curves and the area under the curve (AUC). Harrell\u0026rsquo;s concordance index (C-index) was calculated for each model to determine which index had a predictive association with the endpoints. Bootstrapping method was used to calculate 95% confidence intervals (CI). P-values\u0026thinsp;\u0026lt;\u0026thinsp;0.05 were considered statistically significant. Calculations were performed using JMP v17 (SAS Institute, Cary, NC, USA) and EZR Ver 1.61 (Saitama Medical Center, Jichi Medical University, Saitama, Japan) [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e].\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eCharacteristics of patients with CRC in single-center study\u003c/h2\u003e \u003cp\u003eAmong 663 patients who underwent R0 curative resection of stage I\u0026ndash;III CRC between April 2010 and December 2018 at our institute, 608 patients were enrolled in single-center study, excluding 55 patients because of the exclusion criteria. Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e summarizes the characteristics of the patients in single-institution study. The median age of the patients was 67 years, with more men than women among the patients enrolled. The median CEA and CA19-9 were 2.9 ng/mL and 6.0 U/mL, respectively. Overall, 87 patients (14.3%) experienced recurrence. Figure\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e presents a comparison of ROC curve analysis for each IBPS with reference to OS after surgery. The AUC value of the CALLY index was 0.6549, which was higher than that of the other indices (PNI, 0.5982; NLR, 0.5694; mGPS, 0.5954).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003ePatient characteristics in single-center study\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCharacteristics\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePatients (n\u0026thinsp;=\u0026thinsp;608)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale/Female\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e371/237\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge (years)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e67 (61\u0026ndash;75)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBMI (kg/m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e22.6 (20.4\u0026ndash;24.6)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eASA-PS\u0026thinsp;\u0026ge;\u0026thinsp;3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e33 (5.4%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHTN (+)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e231 (38.0%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDM (+)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e124 (20.4%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDL (+)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e186 (30.6%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVentilatory disease (+)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e47 (7.7%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMedication: antiplatelet or coagulation agent\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e74 (12.2%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCEA (ng/mL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.9 (1.8\u0026ndash;5.6)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCA19-9 (U/mL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6.0 (3.0\u0026ndash;13.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePNI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e51.4 (47.1\u0026ndash;54.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCALLY index\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8.4 (2.5\u0026ndash;19.8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNLR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.3 (1.7\u0026ndash;3.2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003emGPS 0/1/2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e495/87/26\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTumor localization: colon/rectum\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e335/273\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003epT\u0026thinsp;\u0026ge;\u0026thinsp;4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e32 (5.3%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003epN (+)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e177 (19.1%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHistology: other than differentiated carcinoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e76 (12.6%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVascular invasion (+)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e385 (63.5%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"2\"\u003eContinuous variables are expressed as medians (interquartile ranges). Qualitative variables are expressed as numbers (%). Abbreviations: BMI, body mass index; ASA-PS, American Society of Anesthesiologists Physical Status; HTN, hypertension; DM, diabetes mellitus; DL, dyslipidemia; CEA, carcinoembryonic antigen; CA19-9, carbohydrate antigen 19\u0026thinsp;\u0026minus;\u0026thinsp;9; PNI, prognostic nutrition index; CALLY index, C-reactive protein-albumin-lymphocyte index; NLR, neutrophile/lymphocyte ratio; mGPS, modified Glasgow prognostic score.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003cb\u003eComparison of univariate and multivariate analyses of prognostic factors for OS and RFS in patients with stage I-III CRC in single-center study\u003c/b\u003e \u003c/p\u003e \u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e summarizes the results of univariate and multivariate analyses of prognostic factors for OS in a single-center study. In the univariate analysis, statistically significant prognostic factors for poor OS were age\u0026thinsp;\u0026ge;\u0026thinsp;75 (year) (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.0074), American society of Anesthesiologists Physical Status (ASA-PS)\u0026thinsp;\u0026ge;\u0026thinsp;3 (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.0049), diabetes mellitus (DM) (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.0102), carcinoembryonic antigen (CEA)\u0026thinsp;\u0026gt;\u0026thinsp;5 (ng/mL) (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.0001), carbohydrate antigen 19\u0026thinsp;\u0026minus;\u0026thinsp;9 (CA19-9)\u0026thinsp;\u0026gt;\u0026thinsp;37 (U/mL) (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.0001), PNI\u0026thinsp;\u0026le;\u0026thinsp;46 (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.0054), CALLY index\u0026thinsp;\u0026le;\u0026thinsp;3.35 (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.0001), NLR\u0026thinsp;\u0026gt;\u0026thinsp;3.0 (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.0063), mGPS\u0026thinsp;\u0026ge;\u0026thinsp;1 (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.0014), open surgery (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.0256), intraoperative blood transfusion (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.0023), pT\u0026thinsp;\u0026ge;\u0026thinsp;4 (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.0419), pathological positivity of lymph node metastasis (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.0001), and positivity of vascular invasion (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.0251). In the multivariate analysis, the following six factors were identified as prognostic factors for poor OS in patients: age\u0026thinsp;\u0026ge;\u0026thinsp;75 (year) (hazard ratio [HR]\u0026thinsp;=\u0026thinsp;2.154; 95% CI\u0026thinsp;=\u0026thinsp;1.21\u0026ndash;3.82, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.0087), ASA-PS\u0026thinsp;\u0026ge;\u0026thinsp;3 (HR\u0026thinsp;=\u0026thinsp;2.816; 95% CI\u0026thinsp;=\u0026thinsp;1.13\u0026ndash;6.99, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.0256), CEA\u0026thinsp;\u0026gt;\u0026thinsp;5 (ng/mL) (HR\u0026thinsp;=\u0026thinsp;1.938; 95% CI\u0026thinsp;=\u0026thinsp;1.09\u0026ndash;3.44, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.0241), CA19-9\u0026thinsp;\u0026gt;\u0026thinsp;37 (U/mL) (HR\u0026thinsp;=\u0026thinsp;3.126; 95% CI\u0026thinsp;=\u0026thinsp;1.50\u0026ndash;6.49, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.0022), CALLY index\u0026thinsp;\u0026le;\u0026thinsp;3.35 (HR\u0026thinsp;=\u0026thinsp;2.069; 95% CI\u0026thinsp;=\u0026thinsp;1.20\u0026ndash;3.57, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.0091), and pathological positivity of lymph node metastasis (HR\u0026thinsp;=\u0026thinsp;3.108; 95% CI\u0026thinsp;=\u0026thinsp;1.80\u0026ndash;5.36, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.0001).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eUnivariate and multivariate analyses of prognostic factor for overall survival in single-center study\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"8\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eVariables\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eUnivariate\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eMultivariate\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eN\u0026thinsp;=\u0026thinsp;608\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eHR\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e95% CI\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e-value\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eHR\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003e95% CI\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e371\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.221\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.70\u0026ndash;2.12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.4775\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1.725\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.97\u0026ndash;3.08\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.0658\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge (year)\u0026thinsp;\u0026ge;\u0026thinsp;75\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e153\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2.138\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.23\u0026ndash;3.73\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.0074\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e2.154\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e1.21\u0026ndash;3.82\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e\u003cb\u003e0.0087\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBMI (kg/m\u003csup\u003e2\u003c/sup\u003e)\u0026thinsp;\u0026lt;\u0026thinsp;25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e131\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.764\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.83\u0026ndash;3.73\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.1367\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eASA-PS\u0026thinsp;\u0026ge;\u0026thinsp;3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e33\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e3.397\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.45\u0026ndash;7.96\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.0049\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e2.816\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e1.13\u0026ndash;6.99\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e\u003cb\u003e0.0256\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHTN (+)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e231\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.398\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.82\u0026ndash;2.37\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.2139\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDM (+)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e124\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2.063\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.19\u0026ndash;3.58\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.0102\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDL (+)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e186\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.057\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.61\u0026ndash;1.84\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.8440\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVentilatory disease (+)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e47\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.253\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.50\u0026ndash;3.14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.6310\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMedications: antiplatelet or coagulation agents\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e74\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.525\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.75\u0026ndash;3.11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.2461\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCEA (ng/mL)\u0026thinsp;\u0026gt;\u0026thinsp;5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e165\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e3.133\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.86\u0026ndash;5.28\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.0001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1.938\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e1.09\u0026ndash;3.44\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e\u003cb\u003e0.0241\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCA19-9 (U/mL)\u0026thinsp;\u0026gt;\u0026thinsp;37\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e38\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e5.083\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e2.68\u0026ndash;9.65\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.0001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e3.126\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e1.50\u0026ndash;6.49\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e\u003cb\u003e0.0022\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePNI\u0026thinsp;\u0026le;\u0026thinsp;46\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e113\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2.213\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.27\u0026ndash;3.87\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.0054\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCALLY index\u0026thinsp;\u0026le;\u0026thinsp;3.35\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e177\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2.909\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.73\u0026ndash;4.90\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.0001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e2.069\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e1.20\u0026ndash;3.57\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e\u003cb\u003e0.0091\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNLR\u0026thinsp;\u0026gt;\u0026thinsp;3.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e177\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2.070\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.23\u0026ndash;3.49\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.0063\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003emGPS\u0026thinsp;\u0026ge;\u0026thinsp;1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e113\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2.440\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.41\u0026ndash;4.21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.0014\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOpen surgery\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e108\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.932\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.08\u0026ndash;3.44\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.0256\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOperative time (min)\u0026thinsp;\u0026ge;\u0026thinsp;280\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e297\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.500\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.87\u0026ndash;2.57\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.1406\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBlood loss (mL)\u0026thinsp;\u0026ge;\u0026thinsp;60\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e309\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.447\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.85\u0026ndash;2.48\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.1774\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIntraoperative blood transfusion (+)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e3.737\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.60\u0026ndash;8.73\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.0023\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTumor localization: Rectum\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e273\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.350\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.80\u0026ndash;2.27\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.2576\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003epT\u0026thinsp;\u0026ge;\u0026thinsp;4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e32\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2.488\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.03\u0026ndash;5.08\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.0419\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003epN (+)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e177\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e3.051\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.80\u0026ndash;5.18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.0001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e3.108\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e1.80\u0026ndash;5.36\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.0001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHistology: other than differentiated carcinoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e76\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.527\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.77\u0026ndash;3.03\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.2258\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVascular invasion (+)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e385\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2.194\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.10\u0026ndash;4.36\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.0251\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePostoperative chemotherapy (+)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e197\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.167\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.69\u0026ndash;1.99\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.5699\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePostoperative complications CD\u0026thinsp;\u0026ge;\u0026thinsp;3 (+)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e45\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.672\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.76\u0026ndash;3.70\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.2041\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"8\"\u003eThe variables in bold are statistically significant (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05). Abbreviations: HR, hazard ratio; CI, confidence interval; BMI, body mass index; ASA-PS, American Society of Anesthesiologists Physical Status; HTN, hypertension; DM, diabetes mellitus; DL, dyslipidemia; CEA, carcinoembryonic antigen; CA19-9, carbohydrate antigen 19\u0026thinsp;\u0026minus;\u0026thinsp;9; PNI, prognostic nutrition index; CALLY index, C-reactive protein-albumin-lymphocyte index; NLR, neutrophil/lymphocyte ratio; mGPS, modified Glasgow prognostic score; CD, Clavien-Dindo.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e summarizes the results of univariate and multivariate analyses of prognostic factors for RFS in a single-center study. In the univariate analysis, statistically significant prognostic factors for poor RFS were as follows: male (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.0202), ASA-PS\u0026thinsp;\u0026ge;\u0026thinsp;3 (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.0043), DM (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.0266), CEA\u0026thinsp;\u0026gt;\u0026thinsp;5 (ng/mL) (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.0001), CA19-9\u0026thinsp;\u0026gt;\u0026thinsp;37 (U/mL) (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.0001), PNI\u0026thinsp;\u0026le;\u0026thinsp;46 (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.0116), CALLY index\u0026thinsp;\u0026le;\u0026thinsp;3.35 (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.0022), NLR\u0026thinsp;\u0026gt;\u0026thinsp;3.0 (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.0076), mGPS\u0026thinsp;\u0026ge;\u0026thinsp;1 (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.0005), open surgery (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.0109), operative time\u0026thinsp;\u0026ge;\u0026thinsp;280 (min) (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.0014), blood loss\u0026thinsp;\u0026ge;\u0026thinsp;60 (mL) (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.0029), rectal cancer (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.0006), pT\u0026thinsp;\u0026ge;\u0026thinsp;4 (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.0021), pathological positivity of lymph node metastasis (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.0001), positivity of vascular invasion (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.0006), and postoperative chemotherapy (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.0039). In the multivariate analysis, the following seven factors were identified as prognostic factors for poor RFS: male (HR\u0026thinsp;=\u0026thinsp;1.789; 95% CI\u0026thinsp;=\u0026thinsp;1.17\u0026ndash;2.72, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.0068), ASA-PS\u0026thinsp;\u0026ge;\u0026thinsp;3 (HR\u0026thinsp;=\u0026thinsp;2.599; 95% CI\u0026thinsp;=\u0026thinsp;1.32\u0026ndash;5.12, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.0058), CEA\u0026thinsp;\u0026gt;\u0026thinsp;5 (ng/mL) (HR\u0026thinsp;=\u0026thinsp;2.136; 95% CI\u0026thinsp;=\u0026thinsp;1.44\u0026ndash;3.17, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.0002), CA19-9\u0026thinsp;\u0026gt;\u0026thinsp;37 (U/mL) (HR\u0026thinsp;=\u0026thinsp;2.006; 95% CI\u0026thinsp;=\u0026thinsp;1.13\u0026ndash;3.57, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.0177), CALLY index\u0026thinsp;\u0026le;\u0026thinsp;3.35 (HR\u0026thinsp;=\u0026thinsp;1.556; 95% CI\u0026thinsp;=\u0026thinsp;1.05\u0026ndash;2.31, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.0289), rectal cancer (HR\u0026thinsp;=\u0026thinsp;1.891; 95% CI\u0026thinsp;=\u0026thinsp;1.28\u0026ndash;2.79, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.0013), and pathological positivity of lymph node metastasis (HR\u0026thinsp;=\u0026thinsp;2.796; 95% CI\u0026thinsp;=\u0026thinsp;1.91\u0026ndash;4.09, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.0001). Figures\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e summarizes the Kaplan\u0026ndash;Meier analysis showing OS and RFS in a single-center study using the CALLY index. The low CALLY index was associated with poor OS and RFS (OS: \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.0001; log-rank test; Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003ea, RFS: \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.0019; log-rank test; Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eb).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eUnivariate and multivariate analyses of prognostic factor for recurrence-free survival in single-center study\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"8\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eVariables\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eUnivariate\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eMultivariate\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eN\u0026thinsp;=\u0026thinsp;608\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eHR\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e95% CI\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e-value\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eHR\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003e95% CI\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e371\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.627\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.08\u0026ndash;2.45\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.0202\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1.789\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e1.17\u0026ndash;2.72\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e\u003cb\u003e0.0068\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge (year)\u0026thinsp;\u0026ge;\u0026thinsp;75\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e153\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.987\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.63\u0026ndash;1.54\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.9531\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBMI (kg/m\u003csup\u003e2\u003c/sup\u003e)\u0026thinsp;\u0026lt;\u0026thinsp;25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e131\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.536\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.93\u0026ndash;2.54\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.0956\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eASA-PS\u0026thinsp;\u0026ge;\u0026thinsp;3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e33\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2.578\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.34\u0026ndash;4.94\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.0043\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e2.599\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e1.32\u0026ndash;5.12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e\u003cb\u003e0.0058\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHTN (+)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e231\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.122\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.76\u0026ndash;1.65\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.5556\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDM (+)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e124\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.600\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.06\u0026ndash;2.42\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.0266\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDL (+)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e186\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.131\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.76\u0026ndash;1.68\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.5398\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVentilatory disease (+)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e47\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.057\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.53\u0026ndash;2.09\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.8731\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMedications: antiplatelet or coagulation agents\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e74\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.9323\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.52\u0026ndash;1.67\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.8128\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCEA (ng/mL)\u0026thinsp;\u0026gt;\u0026thinsp;5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e165\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2.873\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.98\u0026ndash;4.17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.0001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e2.136\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e1.44\u0026ndash;3.17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e\u003cb\u003e0.0002\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCA19-9 (U/mL)\u0026thinsp;\u0026gt;\u0026thinsp;37\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e38\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2.915\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.69\u0026ndash;5.03\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.0001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e2.006\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e1.13\u0026ndash;3.57\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e\u003cb\u003e0.0177\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePNI\u0026thinsp;\u0026le;\u0026thinsp;46\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e113\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.728\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.13\u0026ndash;2.64\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.0116\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCALLY index\u0026thinsp;\u0026le;\u0026thinsp;3.35\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e177\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.812\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.24\u0026ndash;2.65\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.0022\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1.556\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e1.05\u0026ndash;2.31\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e\u003cb\u003e0.0289\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNLR\u0026thinsp;\u0026gt;\u0026thinsp;3.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e177\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.681\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.15\u0026ndash;2.46\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.0076\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003emGPS\u0026thinsp;\u0026ge;\u0026thinsp;1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e113\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2.070\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.38\u0026ndash;3.11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.0005\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOpen surgery\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e108\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.745\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.14\u0026ndash;2.68\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.0109\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOperative time (min)\u0026thinsp;\u0026ge;\u0026thinsp;280\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e297\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.894\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.28\u0026ndash;2.81\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.0014\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBlood loss (mL)\u0026thinsp;\u0026ge;\u0026thinsp;60\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e309\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.801\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.22\u0026ndash;2.65\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.0029\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIntraoperative Blood transfusion (+)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2.024\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.94\u0026ndash;4.36\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.0717\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTumor localization: Rectum\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e273\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.943\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.33\u0026ndash;2.85\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.0006\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1.891\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e1.28\u0026ndash;2.79\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e\u003cb\u003e0.0013\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003epT\u0026thinsp;\u0026ge;\u0026thinsp;4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e32\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2.577\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.41\u0026ndash;4.71\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.0021\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003epN (+)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e177\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2.701\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.86\u0026ndash;3.92\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.0001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e2.796\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e1.91\u0026ndash;4.09\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.0001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHistology: other than differentiated carcinoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e76\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.061\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.60\u0026ndash;1.86\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.8364\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVascular invasion (+)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e385\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2.276\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.43\u0026ndash;3.63\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.0006\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePostoperative chemotherapy (+)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e197\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.736\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.19\u0026ndash;2.53\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.0039\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePostoperative complications CD\u0026thinsp;\u0026ge;\u0026thinsp;3 (+)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e45\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.413\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.76\u0026ndash;2.64\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.2768\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"8\"\u003eThe variables in bold are statistically significant (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05). Abbreviations: HR, hazard ratio; CI, confidence interval; BMI, body mass index; ASA-PS, American Society of Anesthesiologists Physical Status; HTN, hypertension; DM, diabetes mellitus; DL, dyslipidemia; CEA, carcinoembryonic antigen; CA19-9, carbohydrate antigen 19\u0026thinsp;\u0026minus;\u0026thinsp;9; PNI, prognostic nutrition index; CALLY index, C-reactive protein-albumin-lymphocyte index; NLR, neutrophil/lymphocyte ratio; mGPS, modified Glasgow prognostic score; CD, Clavien-Dindo.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003eComparison of backgrounds by preoperative CALLY index in single-center study\u003c/h2\u003e \u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e summarizes the characteristics of the patients in the high and low CALLY index groups in this single-center study. Compared with the low-CALLY index group, the high-CALLY index group included younger patients (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.0004), higher body mass index (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.0160), less patients with ASA-PS\u0026thinsp;\u0026ge;\u0026thinsp;3 (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.0001), less patients with DM (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.0486), less patients with ventilatory disease (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.0347), less patients who underwent open surgery (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.0001), and less patients with intraoperative blood transfusion (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.0001). Intraoperative blood loss (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.0001) and the number of patients with deeper tumor invasion (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.0001) were higher in the low-CALLY-index group than in the high-CALLY index group. Tumor marker levels were higher in the low-CALLY index group than in the high-CALLY index group (CEA: \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.0001, CA19-9: \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.0009). Among the IBPS, the PNI (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.0001), NLR (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.0001), and mGPS (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.0001) were significantly different between the two groups.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eComparison of patient characteristics with high- and low-CALLY index group in single-center study\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHigh-CALLY index group (n\u0026thinsp;=\u0026thinsp;431)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eLow-CALLY index group (n\u0026thinsp;=\u0026thinsp;177)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge (year)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e66 (60\u0026ndash;73)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e69 (63\u0026ndash;78)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.0004\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSex (M/F)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e259/172\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e112/65\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.4646\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBMI (kg/m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e22.8 (20.6\u0026ndash;24.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e21.9 (19.7\u0026ndash;24.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.0160\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eASA-PS\u0026thinsp;\u0026ge;\u0026thinsp;3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12 (2.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e21 (11.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.0001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHTN (+)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e157 (36.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e74 (41.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.2143\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDM (+)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e79 (18.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e45 (25.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.0486\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDL (+)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e137 (31.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e49 (27.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.3186\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVentilatory disease (+)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e27 (6.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e20 (11.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.0347\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMedication: antiplatelet or coagulation agent\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e49 (11.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e25 (14.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.3452\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLymphocyte count (/\u0026micro;L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1668 (1336\u0026ndash;2098)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1410 (1008\u0026ndash;1913)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.0001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAlb (g/dL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4.4 (4.1\u0026ndash;4.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.9 (3.5\u0026ndash;4.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.0001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCRP (mg/dL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.05 (0.02\u0026ndash;0.10)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.56 (0.29\u0026ndash;1.09)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.0001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCEA (ng/mL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.6 (1.6\u0026ndash;4.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.5 (2.3\u0026ndash;7.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.0001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCA19-9 (U/mL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6.0 (3.0\u0026ndash;11.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8.0 (3.0\u0026ndash;19.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.0009\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePNI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e52.5 (49.3\u0026ndash;55.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e46.3 (40.7\u0026ndash;51.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.0001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNLR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.1 (1.5\u0026ndash;2.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.1 (2.1\u0026ndash;4.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.0001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003emGPS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e426/5/0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e69/82/26\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.0001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOpen/Laparoscopic or robot-assisted\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e51/380\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e57/120\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.0001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOperative time (min)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e284 (237\u0026ndash;356)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e275 (223\u0026ndash;352)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.5538\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBlood loss (ml)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e50 (26\u0026ndash;123)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e81 (35\u0026ndash;279)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.0001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIntraoperative blood transfusion (+)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9 (2.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e16 (9.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.0001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTumor localization: colon/rectum\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e228/203\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e107/70\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.0890\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003epT (1/2/3/4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e155/95/167/14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e37/25/97/18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.0001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003epN (+)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e124 (28.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e53 (29.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.7724\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHistology: other than differentiated carcinoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e47 (11.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e29 (16.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.0681\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVascular invasion (+)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e267 (62.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e118 (67.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.2502\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePostoperative chemotherapy (+)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e143 (33.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e54 (30.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.5228\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePostoperative complications CD\u0026thinsp;\u0026ge;\u0026thinsp;3 (+)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e31 (7.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14 (7.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.7570\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eThe variables in bold are statistically significant (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05). Continuous variables are expressed as medians (interquartile ranges). Qualitative variables are expressed as numbers (%). Abbreviations: M, male; F, female; BMI, body mass index; ASA-PS, American Society of Anesthesiologists Physical Status; HTN, hypertension; DM, diabetes mellitus; DL, dyslipidemia; Alb, albumin; CRP, C-reactive protein; CEA, carcinoembryonic antigen; CA19-9, carbohydrate antigen 19\u0026thinsp;\u0026minus;\u0026thinsp;9; PNI, prognostic nutrition index; NLR, neutrophile/lymphocyte ratio; mGPS, modified Glasgow prognostic score; CD, Clavien-Dindo.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003eComparison of inflammation-based prognostic scores for OS and RFS in single-center study\u003c/h2\u003e \u003cp\u003eFigure \u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e summarizes the comparison of time-dependent ROC curve of IBPS for OS and RFS in single-center study. A time-dependent ROC curve was used to calculate the AUC values at different time points. In terms of both OS and RFS, Harrell\u0026rsquo;s concordance index (C-index) values for the CALLY index were superior than those for other IBPS after surgery (OS: CALLY index, 0.655; 95% CI\u0026thinsp;=\u0026thinsp;0.571\u0026ndash;0.739, SE\u0026thinsp;=\u0026thinsp;0.043; PNI, 0.616; 95% CI\u0026thinsp;=\u0026thinsp;0.522\u0026ndash;0.803, SE\u0026thinsp;=\u0026thinsp;0.046; NLR, 0.574; 95% CI\u0026thinsp;=\u0026thinsp;0.487\u0026ndash;0.663, SE\u0026thinsp;=\u0026thinsp;0.046; mGPS, 0.593; 95% CI\u0026thinsp;=\u0026thinsp;0.520\u0026ndash;0.665, SE\u0026thinsp;=\u0026thinsp;0.037; Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003ea, RFS: CALLY index, 0.598; 95% CI\u0026thinsp;=\u0026thinsp;0.542\u0026ndash;0.656, SE\u0026thinsp;=\u0026thinsp;0.030; PNI, 0.580; 95% CI\u0026thinsp;=\u0026thinsp;0.521\u0026ndash;0.637, SE\u0026thinsp;=\u0026thinsp;0.030; NLR, 0.586; 95% CI\u0026thinsp;=\u0026thinsp;0.530\u0026ndash;0.641, SE\u0026thinsp;=\u0026thinsp;0.023; mGPS, 0.564; 95% CI\u0026thinsp;=\u0026thinsp;0.520\u0026ndash;0.612, SE\u0026thinsp;=\u0026thinsp;0.023; Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eb).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003cb\u003eExternal multi-center analysis of the CALLY index associated with prognosis of stage I-III CRC following curative resection\u003c/b\u003e \u003c/p\u003e \u003cp\u003eTo confirm the applicability of the cut-off value of the CALLY index, which was identified as a prognostic factor following curative resection for CRC based on our institutional study, we conducted a survival time analysis using the HiSCO multi-center dataset, which included a larger population. Figure\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e summarizes the Kaplan\u0026ndash;Meier analysis showing OS and RFS in a multi-center study using the CALLY index with a cutoff value determined in a single-center study. A low CALLY index was associated with poor OS and RFS (OS: \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.0001, log-rank test; Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003ea; RFS: \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.0001, log-rank test; Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003eb). Supplemental Table\u0026nbsp;1 summarizes the characteristics of the patients in the high- and low-CALLY index groups in the multi-center study. Compared with the low-CALLY index group, the high-CALLY index group included younger patients (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.0001), less patients with ASA-PS\u0026thinsp;\u0026ge;\u0026thinsp;3 (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.0001). The number of patients with deeper tumor invasion (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.0001) were higher in the low-CALLY-index group than in the high-CALLY index group. Tumor marker levels were higher in the low CALLY index group than in the high CALLY index group (CEA, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.0001; CA19-9, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.0002). The above results of the multi-center study were similar to those of the single-center study.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis retrospective study investigated prognostic factors, which include IBPS, affecting long-term prognosis in patients who underwent curative resection for stage I\u0026ndash;III CRC. In addition to severe systemic condition and tumor factors such as tumor markers and lymph node metastasis, preoperative low CALLY index, an inflammation-based marker, was associated with poor long-term prognosis in patients with stage I\u0026ndash;III CRC following curative resection. CRC is the most frequently diagnosed gastrointestinal cancer. It ranks third in both incidence and mortality in males, and second in incidence and third in mortality in females worldwide [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Various factors such as age, postoperative complication, tumor-node-metastasis (TNM) stage, tumor marker, tumor differentiation, and circulating tumor cells, have been reported as prognostic factors affecting the postoperative outcome of stage I\u0026ndash;III CRC [\u003cspan additionalcitationids=\"CR20\" citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. In this study, age, male, severe systemic condition, comorbidities, and tumor factors were identified as factors affecting postoperative prognosis of CRC, which was consistent with the results of previous studies. Interestingly, among the IBPS compared in this study, only the CALLY index was identified as a useful postoperative prognostic indicator following curative resection for CRC. The CALLY index, which is calculated from CRP and Alb reflecting inflammation, and lymphocyte counts reflecting immune function, was reported as an IBPS, and as a postoperative prognostic predictor for hepatocellular carcinoma [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. The CALLY index is being increasingly reported as being associated with prognosis for various types of carcinomas [\u003cspan additionalcitationids=\"CR12 CR13\" citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. In this study, compared to other IBPS, the CALLY index was an accurate prognostic indicator, and a low CALLY index was an independent poor prognostic factor for stage I\u0026ndash;III CRC after curative resection. Both single- and multi-center studies have shown that a low CALLY index is associated with poor postoperative prognosis in patients with CRC and is strongly related to age and tumor factors. In addition, the preoperative CALLY index was found to be a better predictor of prognosis than the other markers in a time-dependent ROC curve for OS and RFS in single-center study. This index reflects inflammation and may be a sensitive indicator of preoperative systemic status, and it can be considered useful in predicting postoperative outcomes for patients with various types of cancers.\u003c/p\u003e \u003cp\u003eCancer development and progression have been shown to be closely associated with the host nutritional status and inflammatory responses within the tumor microenvironment [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]; high CRP and low Alb levels were reported as factors for poor survival in patients with CRC [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. Peripheral lymphocyte count has also been reported as a prognostic indicator of patients with CRC [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. In patients with cancer, Alb values and lymphocyte counts are reduced, and the CRP values are elevated owing to inflammation, poor nutrition, and a weakened immune system; various IBPS calculated from CRP and Alb which are called inflammatory markers, and lymphocyte, which is a surrogate marker of immunocompetence, were already reported as prognostic indicators for CRC following curative resection [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. Because the CALLY index is calculated from three factors mentioned above, it more accurately reflects the inflammatory responses within the tumor microenvironment and may be a more sensitive marker for the prognosis of various cancers than other IBPS. In fact, this study revealed that the CALLY index is associated with tumor markers and tumor depth, and it was found to be the most sensitive prognostic indicator for patients with stage I\u0026ndash;III CRC following curative resection among the IBPS examined in this study. The CALLY index is considered as an extremely useful marker to identify the patients at risk of poor prognosis and to establish appropriate treatment strategies. In addition, another reason why the CALLY index is considered a valuable prognostic indicator for patients with stage I\u0026ndash;III CRC following curative resection is its susceptibility to the influence of age.\u003c/p\u003e \u003cp\u003eThe prevalence of cancer in older patients is increasing, and by 2030, approximately 70% of all new cancer cases will be diagnosed in individuals aged\u0026thinsp;\u0026ge;\u0026thinsp;65 years [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. In this study, it was confirmed that age, a known prognostic factor for postoperative CRC, is associated with the CALLY index. Generally, older patients have age-related declines in organ function and immunity [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e], and a relation between aging and decreased lymphocyte counts has been reported [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]. Recently, frailty has also been reported as a poor prognostic factor for stage I\u0026ndash;III CRC following curative resection [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]; elevated CRP and hypoalbuminemia, which lead to chronic inflammation in older patients, have been suggested as candidate indicators for frailty [\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]. In other words, the three factors mentioned above, which are components of the CALLY index, are also considered to be affected by not only tumor factors but also aging. Based on the above, the CALLY index, which is influenced by age, may be considered as an accurate prognostic indicator after surgery for various types of cancers, including CRC.\u003c/p\u003e \u003cp\u003eThis study has several limitations. First, its retrospective design. Second, all common postoperative prognostic factors for CRC reported in previous studies were not included in the analysis. Third, the cohorts for biological markers such as RAS, BRAF, and MSI had a limited sample size and could not be included in the analysis. Therefore, more analyses are needed to confirm whether these results are similar to those of the present study after accumulating more cases of these biological markers. However, the results of this study, including single- and multi-center analyses, show that the CALLY index is a good prognostic indicator for patients with CRC following curative resection.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eLow preoperative CALLY index was found to be independently associated with poor prognosis in patients with stage I\u0026ndash;III CRC after curative resection. Preoperative CALLY index was a useful assessment index for predicting the prognosis of patients who underwent curative resection of stage I\u0026ndash;III CRC. Further studies investigating the association between CALLY index and CRC prognosis are warranted.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eData availability\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThis study did not receive any specific grants from funding agencies in the public, commercial, or non-profit sectors.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors have no relevant financial or non-financial interests to disclose.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contributions:\u0026nbsp;\u003c/strong\u003eTB, TY, SA and MS drafted the manuscript. MH contributed to the interpretation of data and analysis. HO substantively revised the manuscript. All the authors have cooperated in the accumulation of cases and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics statements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThere is no need for consent to participate to be obtained due to retrospective study. Administrative permissions were not required to access and use the medical records described in this study. This study was authorized in advance by the institutional review board of the Hiroshima University Hospital (approval number: E-744-4, E-2527).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe thank all the members of\u0026nbsp;the Hiroshima Surgical\u0026nbsp;study group of Clinical Oncology. We would like to thank Editage (www.editage.com\u003c/a\u003e) for the English language editing.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eSung H, Ferlay J, Siegel RL et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. \u003cem\u003eCA Cancer J Clin.\u003c/em\u003e 2021; 71: 209\u0026ndash;249.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMantovani A, Allavena P, Sica A, Balkwill F. Cancer-related inflammation. Nature 2008; 454: 436\u0026ndash;444.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBalkwill F, Mantovani A. Inflammation and cancer: back to Virchow? Lancet. 2001; 357: 539\u0026ndash;545.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDiakos CI, Charles KA, McMillan DC, Clarke SJ. Cancer-related inflammation and treatment effectiveness. 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Bone Marrow Transplant. 2013;48:452\u0026ndash;458.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eUen YH, Lu CY, Tsai HL et al. Persistent presence of postoperative circulating tumor cells is a poor prognostic factor for patients with stage I-III colorectal cancer after curative resection. Ann Surg Oncol 2008; 15: 2120\u0026ndash;2128.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMehrkhani F, Nasiri S, Donboli K et al. Prognostic factors in survival of colorectal cancer patients after surgery. Colorectal Dis. 2009; 11: 157\u0026ndash;161.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMiyamoto Y, Hiyoshi Y, Tokunaga R et al. Postoperative complications are associated with poor survival outcome after curative resection for colorectal cancer: A propensity-score analysis. J Surg Oncol. 2020; 122: 344\u0026ndash;349.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMichels KB. The role of nutrition in cancer development and prevention. Int J Cancer. 2005; 114: 163\u0026ndash;165.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTaniguchi K, Karin M. NF-κB, inflammation, immunity and cancer: coming of age. Nat Rev Immunol. 2018; 18: 309\u0026ndash;324.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLai CC, You JF, Yeh CY et al. Low preoperative serum albumin in colon cancer: a risk factor for poor outcome. Int J Colorectal Dis. 2011; 26: 473\u0026ndash;481.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSwede H, Hajduk AM, Sharma J et al. Baseline serum C-reactive protein and death from colorectal cancer in the NHANES III cohort. Int J Cancer. 2014; 134: 1862\u0026ndash;1870.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eIseki Y, Shibutani M, Maeda K et al. The impact of the preoperative peripheral lymphocyte count and lymphocyte percentage in patients with colorectal cancer. Surg Today. 2017; 47: 743\u0026ndash;754.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGuthrie GJ, Roxburgh CS, Farhan-Alanie OM et al. Comparison of the prognostic value of longitudinal measurements of systemic inflammation in patients undergoing curative resection of colorectal cancer. Br J Cancer. 2013; 109: 24\u0026ndash;28.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSmith BD, Smith GL, Hurria A et al. Future of cancer incidence in the United States: burdens upon an aging, changing nation. J Clinl Oncol. 2009; 27: 2758\u0026ndash;2765.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNikolich-Žugich J. The twilight of immunity: emerging concepts in aging of the immune system. Nat Immunol. 2018; 19: 10\u0026ndash;19.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eErkeller-Yuksel FM, Deneys V, Yuksel B et al. Age-related changes in human blood lymphocyte subpopulations. J Pediatri. 1992; 120: 216\u0026ndash;222.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMima K, Miyanari N, Morito A et al. Frailty is an independent risk factor for recurrence and mortality following curative resection of stage I-III colorectal cancer. Ann Gastroenterol Surg. 2020; 4: 405\u0026ndash;412.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eVelissaris D, Pantzaris N, Koniari I et al. C-Reactive Protein and Frailty in the Elderly: A Literature Review. J Clin Med Res. 2017; 9: 461\u0026ndash;465.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"colorectal cancer, curative resection, C-reactive protein-albumin-lymphocyte index, inflammation-based prognostic scores","lastPublishedDoi":"10.21203/rs.3.rs-4221754/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4221754/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003ePurpose\u003c/h2\u003e \u003cp\u003eRecently, several simple inflammation-based prognostic scores that can be calculated easily from serum parameters, have been reported to be related to colorectal cancer prognosis. This study aimed to investigate factors influencing the prognosis of patients, including inflammation-based prognostic scores, with stage I\u0026ndash;III colorectal cancer following curative resection.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eThis single-center study included 608 patients with stage I\u0026ndash;III colorectal cancer who underwent curative resection between April 2010 and December 2018. A retrospective analysis was performed to identify the prognosis-associated variables in these patients. Next, 1659 patients with stage I\u0026ndash;III colorectal cancer who underwent curative resection from a multi-center database belonging to the Hiroshima Surgical study group of Clinical Oncology were analyzed for survival.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eOf the inflammation-based prognostic scores, only preoperative C-reactive protein-albumin-lymphocyte index was revealed to predict a poor prognosis in patients with stage I\u0026ndash;III colorectal cancer following curative resection. The low C-reactive protein-albumin-lymphocyte index was associated with poor overall survival and recurrence-free survival, which was similar in patients from multi-center database. The C-reactive protein-albumin-lymphocyte index was found to be associated with patient age, systemic condition, comorbidities, and tumor factors. The time-dependent area under the curve for the C-reactive protein-albumin-lymphocyte index was superior to those of other inflammation-based prognostic scores in most postoperative observation periods.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eThe preoperative C-reactive protein-albumin-lymphocyte index was independently associated with long-term prognosis in patients with stage I\u0026ndash;III colorectal cancer following curative resection.\u003c/p\u003e","manuscriptTitle":"C-reactive protein-albumin-lymphocyte index is a useful indicator for recurrence and survival following curative resection of stage I–III colorectal cancer","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-04-10 16:19:17","doi":"10.21203/rs.3.rs-4221754/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"e99551f3-bb2e-4684-82c6-b22fc098900a","owner":[],"postedDate":"April 10th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-05-13T20:23:47+00:00","versionOfRecord":[],"versionCreatedAt":"2024-04-10 16:19:17","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4221754","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4221754","identity":"rs-4221754","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}