Confluence of Preoperative high levels of C-Reactive Protein and Visceral Fat index as Potential Contributor to Postoperative Complications in Colorectal Cancer: a Randomized Clinical Trial Incorporating Parenteral Nutrition

Confluence of Preoperative high levels of C-Reactive Protein and Visceral Fat index as Potential Contributor to Postoperative Complications in Colorectal Cancer: a Randomized Clinical Trial Incorporating Parenteral Nutrition | 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 Confluence of Preoperative high levels of C-Reactive Protein and Visceral Fat index as Potential Contributor to Postoperative Complications in Colorectal Cancer: a Randomized Clinical Trial Incorporating Parenteral Nutrition Francisco López-Rodríguez-Arias, Luis Sánchez-Guillén, Antonio Sanchís-López, and 6 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4325782/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 Background: Visceral fat and inflammatory conditions are risk factors in patients undergoing colorectal cancer (CRC) surgery. This study was conducted to evaluate the effect of early peripheral parenteral nutrition (PPN) in patients with an elevated inflammatory state and/or an increase in their visceral fat on the anastomotic leak of patients undergoing CRC surgery within an enhanced recovery program. Methods: A clinical trial was performed in patients undergoing CRC surgery between October 2016 and September 2019. Patients were randomized into two groups: PPN with periOlimel N4-E and conventional fluid therapy (FT). With C-reactive protein (CRP) values prior to surgery and visceral fat analysis of preoperative computer tomography, patients were stratified according to their risk of anastomotic leakage (AL). AL rates was obtained in each risk group differentiating whether they had received PPN or FT. Results: A total of 116 patients were analyzed; 63 received PPN and 53 FT. Patients with high visceral fat index (VFI) had higher mean postoperative CRP values, especially on the 2nd postoperative day (p<0.05). CRP values prior to surgery ≥5 mg/L and high VFI were associated with an AL rate of 28% (30% FT group vs. 23.5% PPN group): OR (95% CI) of 4.8 (p=0.003), and CRP values ≥10.2 mg/L showed an AL rate of 25.7% (30.8% FT group vs. 22.7% PPN group): OR (95% CI) of 6.6 (p= 0.001). Conclusions: Analysis of visceral fat and the inflammatory state of patients with CRC allows us to evaluate the risk of anastomotic leakage, and PPN should be considered to improve AL rates. Trial registration number: NCT03606863 colorectal anastomotic leakage proinflammatory status visceral fat body composition c-reactive protein parenteral nutrition Figures Figure 1 Figure 2 Figure 3 1. INTRODUCTION Colorectal cancer (CRC) is the third most common type of cancer in the world, with an incidence of 19.5 per 100,000 inhabitants, and it is the second leading cause of cancer death in the world, only behind lung cancer 1 . Surgery is still the main pillar of the treatment of CRC, but despite advances in both technological and postoperative management, it continues to present high rates of complications, with the most feared presence being anastomosis leak (AL), with an incidence between 2.5–33%. Morbidity related with the AL is a determining factor for patient outcome after colorectal surgery and involves many factors related to the underlying disease, hospital setting, surgeon expertise and patient status 2 . Tumor growth may trigger a proinflammatory status in some patients that has been related to poor postoperative outcomes and worse oncological prognosis 3–4 . Therefore, the knowledge of the inflammatory state at the preoperative period would allow initiating an appropriate anti-inflammatory treatment 5 . There is a broad consensus that the evaluation of the systemic inflammatory response with biochemical markers such as C-reactive protein (CRP) will allow us to predict and anticipate postoperative complications in colorectal cancer surgery 6 . Moreover, visceral fat appears to be also associated with increased proinflammatory status of patients 7 favoring a greater inflammatory response after colorectal surgery 8 . CT and magnetic resonance have become the gold standard for measuring the quantitative assessment of visceral fat 9 . Visceral fat has been associated with an increase in postoperative complications 10 and a possible decline in overall survival and disease-free survival as well 11 . In patients subjected to a surgical stress, which conditions an increase in their catabolism, perioperative parenteral nutrition (PPN) can supplement the intake received orally, reducing mortality and infectious complications 12,13 . The main outcome of the study was to evaluate the impact of a proinflammatory status measured by means of CRP and the visceral fat index (VFI) of patients undergoing colorectal cancer as a risk factors of AL. In addition, the possible protective effect of PPN of AL occurrence was also assessed as a secondary outcome. 2. MATERIALS AND METHODS 2.1. Study Design An open, controlled, randomized and one-center superiority clinical trial was conducted to analyze the influence of PPN (PeriOlimel N4-E) versus conventional fluid therapy on AL rates in patients undergoing colorectal surgery based on their proinflammatory status (CRP and VFI). Randomization (1:1) was performed using online randomization software. The investigators, surgeons, patients, and statisticians were unmasked to the group in which the patient was randomly allocated. Between October 2016 and September 2019, patients > 18 years with nonmetastatic colorectal cancer T1-3Nx were selected for inclusion and intervened by members of the Coloproctology Unit following ERAS protocols. The study was conducted according to the Helsinki Declaration, was approved by the ethical committee for clinical research of the hospital and was recorded in Clinical Trials (NCT03606863). All patients were invited to participate and signed an informed consent statement before starting the study. 2.2. Patients Patients at severe nutrition risk (weight loss > 10–15% within 6 months, BMI 5, and preoperative serum albumin < 30 g/L without evidence of liver or kidney dysfunction) 14 , intraoperative diagnosis of carcinomatosis, metastasis, locally advanced (T4) or unresectable tumors were excluded from the study. Other exclusion criteria were emergency surgery, a physical condition IV of the American Society of Anesthesiologists (ASA), kidney failure defined through hemodialysis, liver failure, allergy or sensitivity to egg or soy protein, severe hemorrhagic disorder, congenital abnormality of hyperlipidemia of amino acid metabolism, not accepting or being able to comply with the ERAS protocol and the absence of a CT scan one month before surgery. In addition, for the analysis of anastomotic leakage rates, it was decided to exclude excluded those patients who needed to perform a terminal or protective stoma. 2.3. Intervention Patients were admitted to the hospital the day before surgery, starting three days before an intestinal preparation at home with a low-fiber diet. Hospital pharmacy identified patients who were assigned to the PPN with Peri-Olimel N4-E group that was started one day before surgery and continued for 3 days after surgery. On the other hand, patients assigned to the control group received a standard postoperative FT that was withdrawn when the patient tolerated oral feeding. 2.4. ERAS protocol Patients were evaluated after diagnosis by a colorectal surgeon who reported the study and explained the hospital’s ERAS protocol 16 , emphasizing the importance of early postoperative mobilization. Carboxymaltose-rich drinks were given 12 hours and 2 hours before surgery, and antibiotic prophylaxis was administered following the policy of our center. In the intraoperative period, priority was given to laparoscopic surgery. Goal-directed fluids were administered, and hypothermia, drainage or nasogastric tubes were avoided. Epidural anesthesia (ropivacaine 0.2%) was used only in open procedures. In the postoperative period, opioid-free pain control and prophylactic medication for nausea and vomiting were performed. In addition, oral fluids were administered early in both groups. 2.5. Outcomes The main outcomes gathered were preoperative CRP values and VFI. To classify patients according to their inflammatory state, we used the cutoff point for CPR levels of < 5 or ≥ 5 mg/L obtained by Bert et al. 3 In addition, a ROC curve was performed to estimate the PCR value prior to surgery with a better sensitivity-specificity relationship to predict anastomotic leaks. The cutoff point for the VFI was determined by the 50th percentile of the sample differentiating men and women to classify patients in High or Low. Postoperative complications were collected using the Clavien‒Dindo classification and divided into minor complications (Clavien‒Dindo I-II), which included low-risk events such as infection of the surgical wound or postoperative ileus, and major complications (Clavien‒Dindo III-IV) 15 . Occurrence of AL was also gathered. AL was defined following the International Study Group of Rectal Cancer as a communication between the intra- and extraluminal compartments owing to a defect in the integrity of the intestinal wall at the anastomosis. Detailed criteria were as follows: 1) apparent discharge of gas/pus/feces from the abdominal or pelvic drain; 2) anastomotic defect confirmed by proctoscopy, CT scan using contrast medium or rectal examination (only for ultralow rectal anastomosis); and 3) AL confirmed during reoperation. Severity grading of AL was defined as no active therapeutic intervention (Grade A), active therapeutic intervention but manageable without reintervention (Grade B) or requiring surgical reintervention (Grade C) 16 . Grades A and B were considered minor AL, and Grade C was considered major AL. 2.6. Body composition analysis Patients were classified according to their VFI was assessed from axial slices at the L3 vertebra level on the preoperative CT scan. Figure 1 shows the selection with a sagittal CT image of an axial plane in the third lumbar vertebra, highlighting in yellow the visceral fat area. Images were analyzed using NIH image software ImageJ ( https://imagej.nih.gov.ij/ ) by using a fat threshold of -190 to -30 HU. VFI was obtained by dividing the visceral fat area (VFA) by the height squared. 2.7. Sample Size The sample size was calculated to compare the incidence of postoperative complications between the two groups. With a confidence level of 95% (alpha = 0.05), a potency of 80% (beta = 0.2), bilateral contrast and assuming a loss of 10%, 85 patients per group were required. 2.8. Statistical analysis Data were collected prospectively by an external researcher. Continuous variables are described as medians and standard deviations, the Levene test was employed to verify homogeneity and were compared using the Mann-Whitney U and Student’s t test. Discrete variables were described as frequencies and percentages and were compared with a Chi-square test. Ordinal logistic regressions were designed to assess the ability to predict VFI and PCR values for AL. OR and 95% confidence intervals (CI 95%) for AL were calculated in the different risk groups. P values < 0.05 were considered significant. Data analysis was performed using IBM SPSS Statistics software. 3. RESULTS A total of 170 patients were consecutively allocated for the trial. Fifty-four patients were excluded because they did not meet the previously established criteria: 7 patients for failure following the protocol, 3 for presenting intraoperative metastatic disease, 2 for revocation of consent during the study, 2 for errors in CT image recovery and 40 patients who needed a terminal or protective stoma. Finally, 116 patients were finally randomized; 63 patients received PPN and 53 received conventional FT. Patient’s characteristics are detailed in Table 1 . Table 1 The relationship between clinicopathological characteristics and low or high VFI. Characteristics All, n n = 116 Low VFI, n (%) n = 60 (51.7%) High VFI, n (%) n = 56 (48.3%) P-value Age < 70 years ≥ 75 years 53 (45.7%) 63 (54.3%) 31 (51.7%) 29 (48.3%) 22 (39.3%) 34 (60.7%) 0.181 Sex Male Female 69 (59.5%) 47 (40.5%) 37 (61.7%) 23 (38.3%) 32 (57.1%) 24 (42.9) 0.620 ASA score I-II III 70 (60.3%) 46 (39.7%) 42 (70%) 18 (30%) 28 (50%) 28 (50%) 0.028 Perioperative nutrition NPP group FT group 63 (54.3%) 53 (45.7%) 31 (45.6%) 26 (54.4%) 32 (45.8%) 27 (54.2%) 0.99 Preoperative PCR value, mean (SD) 13.6 (28.2) 13.9 ( 32 ) 13.2 (23.8) 0.893 Postoperative complications No Minor (CD I-II) Major (CD III-IV) 78 (67.2%) 21 (22%) 17 (15.3%) 41 (68.3%) 11 (18.3%) 8 (13.3%) 37 (66.1%) 10 (17.9%) 9 (16.1%) 0.917 Anastomosis leak No Minor Major 100 (86.2%) 3 (2.6%) 13 (11.2%) 55 (91.7%) 0 5 (8.3%) 45 (81.4%) 3 (5.1%) 8 (13.6%) 0.078 0.069 0.31 Length of hospital stay, mean (SD) 8.7 (SD 9) 6.8 (4.3) 10.7 (11.8) 0.02 SD: Standard deviation, CD: Clavien Dindo, ASA: American Society of Anesthesiologists, VFI: Visceral Fat Index. FT: Fluid Therapy, PPN: Peripheral parenteral nutrition 3.1. Vascular fat index Patients were classified as having Low VFI or High VFI according to the median values. High VFI was defined for males as > 87.22 cm 2 m 2 and for females as > 71.66 cm 2 m 2 and Low VFI was defined for males as ≤ 87.22 cm 2 m 2 and for females as ≤ 71.66 cm 2 m 2 . The FT and PPN groups showed a similar distribution depending on the VFI. Patients with a high VFI had a higher rate of major and minor AL (18.7% high VFI vs. 8.3% low VFI; p = 0.12) and a longer length of hospital stay (10.7 high VFI vs. 6.8 low VFI; p = 0.02). 3.2. C- reactive protein Association between preoperative and postoperative CRP values and VFI are detailed in Table 2 . Preoperative CRP mean values were not different between VFI groups. However, postoperative mean CRP values were higher in High VFI group, especially on the 2nd postoperative day (p < 0.05). Table 2 The relationship between VFI and CRP values on the day prior to surgery and the first three postoperative days. PCR (mg/L) All, n n = 116 Low VFI, n (%) n = 60 High VFI, n (%) n = 56 P-value POD − 1 13.6 (SD 28.2) 13.8 (SD 32.6) 13.4 (SD 23.4) 0.93 POD + 1 62.2 (SD 49.9) 58.5 (SD 37) 65.8 (SD 53) 0.4 POD + 2 104.48 (SD 75.39) 86.12 (SD 64.63) 117.78 (SD 82.71) < 0.05 POD + 3 96.3 (SD 81.6) 91.08 (SD 84.4) 101.3 (SD 79.2) 0.5 SD: Standard deviation, VFI: Visceral Fat Index, POD: postoperative day. An ordinal logistic regression was performed with an ROC curve associating CRP values before surgery with the presence of AL that obtained a value under the curve of 0.692 (CI 95%: 0.515–0.869; p = 0.025); (Fig. 2 ). The best ratio in our model between sensitivity/1 and specificity was for a CRP value of 10.2 mg/l. Patients with high VFI were more prevalent in the CRP ≥ 5 mg/L group (43.3% low VFI vs. 56.7% high VFI; p = 0.2) and in the CRP ≥ 10.2 mg/L group (40.9% low VFI vs. 59.1% high VFI; p = 0.17). 3.3. Anastomotic leak An ordinal logistic regression was performed with an ROC curve that associated VFI of CT prior to surgery with the presence of AL, presenting a low curve area of 0.56. However, when differentiating between men and women, we observed that the area under the curve was higher in women (0.683, CI 95%: 0.472–0.893; p = 0.115) than in men (0.438, CI 95%: 0.197–0.679;p = 0.0.592). Figure 3 shows the models of the ROC curve that differentiate men and women. The risk of AL was established according to VFI and previous PCR values having received PPN or FT. These data are shown in Table 3 . The different combined risk groups presented an OR (CI 95%) for AL of 1.6 in High VFI (p = 0.08), 3.6 in CRP ≥ 5 mg/dL (p = 0.03), 4.8 in patients with CRP ≥ 5 mg/dL and with High VFI (p = 0.03), 6.6 in ≥ CRP 10.2 mg/dL and 7.3 in patients with CRP ≥ CRP 10.2 mg/dL and with High VIF. A lower rate of AL was observed in patients who received PPN than in those who received FT in the different risk groups. This difference was greater as the risk of AL increased, although statistical significance was not reached. Table 3 Anastomotic leak risk scale based on VFI and previous CRP values and PPN effect. n, % Major Leakage p-value OR (CI 95%) No (n, %) Yes (n, %) Low VFI 60 (51.7%) 55 (91.7) 5 (8.3%) High VFI 56 (48.3%) 48 (85.8%) 8 (14.3%) 0.08 1.6 (0.5–5.3) Control group 4 (14.8%) 2.1 (0.35–12.5) PN group 4 (12.8%) 1.33 (0.27–6.5) CRP < 5 mg/l 67 (58.3%) 63 (94%) 4 (6%) CRP ≥ 5 mg/l 48 (41.7%) 39 (81.2%) 9 (18.8%) 0.03 3.6 (1.05–12.6) Control group 4 (20%) 3.8 (0.62–22.7) PN group 5 (17.9%) 3.6 (0.63–20.11) CRP < 5 mg/l or Low VFI 90 (78.3%) 84 (93.3%) 6 (6.7%) CRP ≥ 5 mg/l and High VFI 25 (21.7%) 18 (72%) 7 (28%) 0.003 4.8 (1.5–15.8) Control group 3 (30%) 5.6 (0.93–33.4) PN group 4 (23.5%) 4.4 (0.87–22.3) CRP < 10.2 mg/L 80 (69.6%) 76 (95%) 4 (5%) CRP ≥ 10.2 mg/l 35 (30.4%) 26 (74.3%) 9 (25.7%) 0.001 6.6 (1.9–23.1) Control group 4 (30.85%) 8.2 (1.3–52.1) PN group 5 (22.7%) 5.7 (1.01–32.5) CRP < 10.2 mg/L or Low VFI 94 (81.7%) 88 (93.6%) 6 (6.4%) CRP ≥ 10.2 mg/l and High VFI 21 (18.3%) 14 (66.7%) 7 (33.3%) < 0.001 7.3 (2.1–25) Control group 3 (37.5%) 8.2 (1.3–52.2) PN group 4 (30.8%) 6.9 (1.3–36.6) CPR: C-reactive protein, VFI: Visceral Fat Index; PN: Parenteral Nutrition; OR: Odds Ratio; CI: Confidence interval 4. DISCUSSION The present study showed an increased risk of AL in patients with a preoperative high inflammatory state and visceral fat index after CRC surgery and evaluated the possible protective effect of PPN against the occurrence of AL. The presence of increased activation of the systemic inflammatory response has been linked to visceral fat 18 . Our analysis showed no differences in mean CRP values prior to surgery based on VFI, but patients with high VFI were more frequent in the CRP groups ≥ 5 mg/dL and ≥ 10.2 mg/dL. Himber C et al. 8 showed in their analysis a correlation between CRP values and VFA measured by CT, although this correlation was weak. In the postoperative period, we observed a difference in CRP values as a function of VFI, reaching statistical significance on the second day. Okamura A. et al. 19 reported a similar relationship between CRP values and VFA in postoperative patients undergoing esophagectomy. Visceral fat has also an important influence on postoperative outcomes 20 . One meta-analysis 21 found a relationship between anastomotic leakage and visceral fat area. Similarly, Kuritzkes et al. 22 performed an ROC curve model that linked the VFA of patients with the ability to predict major complications. Its area under the curve was higher than ours (0.66 vs. 0.56). The cutoff point with the best sensitivity/1-specificity ratio was 191 cm2, which presented an OR of 2 to predict major complications. However, they did not differentiate the analysis according to the patient’s sex. Females are not expected to have a large amount of visceral fat, although having a greater amount of total fat is located preferably in the subcutaneous cell tissue. In males, however, there is a higher ratio of visceral fat/subcutaneous fat 10 . This feature can justify why our ROC curve model has a greater area under the curve in females (0.683 vs. 0.438). CRP measurement allowed for early detection of anastomotic leak in colorectal cancer surgery, us to anticipate their treatment by reducing the impact and morbidity caused by them 23 . CRP is the most commonly used biomarker for its ability to anticipate AL after colorectal surgery and is considered the gold standard in postoperative follow-up 24 . The use of biomarkers of the inflammatory response is also beginning to be used in the preoperative period. AL could be related to an altered inflammatory response, expressed by elevated serological levels of inflammatory markers prior to surgery, such as CRP 25 . The identification of models predicting postoperative complications or specifically anastomotic leakage is one of the current focuses 26,27 . However, most of them use a large number of variables that make it difficult to implement them in normal clinical practice. The determination of factors related to body composition or to patients' presurgery inflammatory state is beginning to be included in these prediction models 28,29 . The PPN complementary to the oral route has demonstrated its benefit in reducing mortality and complications in situations of high energy demand 12,13 , enhancing its protective effect in fragile patients or with low muscle mass 30,31 . PeriOlimel N4-E is a peripheral parenteral nutrition (PPN) with a high content of oleic acid, which in addition to allowing supplementation via the oral route, could help reduce oxidative stress and the inflammatory response after surgery 32 . The current guidelines for clinical practice in surgery advise starting an NP in situations of high risk of malnutrition or after 5 days without achieving a satisfactory oral tolerance and do not individualize the treatment according to muscle reserves or the degree of catabolic response presented by the patient 15,33 . Our analysis shows that the reduction in the rate of anastomosis leakage in patients who have received a complementary PPN is greater in patients with a higher degree of inflammatory activation prior to surgery. To the best of our knowledge, this is the first study to analyze the risk of AL in CRC surgery within an ERAS program based on the patient’s inflammatory state and visceral fat index and to evaluate the possible protective effect of PPN. As limitations of our study, we mainly highlight the low sample size that prevented reaching significant differences in risk group divisions and being a unicentric study. In addition, our risk model for AL is easy to perform, allowing the detection of at-risk patients and the individualization of treatments. 5. CONCLUSIONS Preoperative inflammatory state and body composition of patients should be assessed with enough time previous surgery for its treatment. The measurement of CRP prior to surgery and VFI will allow us to stratify the risk of presenting an AL in the postoperative period. In patients with CRP values before surgery of 5 mg/l and high VFI or with CPR values of 10.2 mg/l, supplement with parenteral nutrition in addition to early oral tolerance should be considered to improve AL rates. Declarations Funding: This study was funded by an investigator-initiated grant from Baxter SL (Spain) to Antonio Arroyo through FISABIO (Foundation for the Promotion of Healthcare and Biomedical Research of the Autonomous Community of Valencia) in Hospital de Elche (Alicante). The sponsor (Baxter) did not participate in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. 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A., Pappou, E. P., Kiran, R. P., Baser, O., Fan, L., Guo, X., Zhao, B., & Bentley-Hibbert, S. (2018). Visceral fat area, not body mass index, predicts postoperative 30-day morbidity in patients undergoing colon resection for cancer. International journal of colorectal disease , 33:1019–1028. doi: 10.1007/s00384-018-3038-2 . Cousin, F., Ortega-Deballon, P., Bourredjem, A., Doussot, A., Giaccaglia, V., & Fournel, I. (2016). Diagnostic Accuracy of Procalcitonin and C-reactive Protein for the Early Diagnosis of Intra-abdominal Infection After Elective Colorectal Surgery: A Meta-analysis. Annals of surgery , 264:252–6. doi: 10.1097/SLA.0000000000001545 . Smith, S. R., Pockney, P., Holmes, R., Doig, F., Attia, J., Holliday, E., Carroll, R., & Draganic, B. (2018). Biomarkers and anastomotic leakage in colorectal surgery: C-reactive protein trajectory is the gold standard. ANZ journal of surgery , 88:440–444. doi: 10.1111/ans.13937 . Holmgren, K., Jonsson, P., Lundin, C., Matthiessen, P., Rutegård, J., Sund, M., & Rutegård, M. (2022). Preoperative biomarkers related to inflammation may identify high-risk anastomoses in colorectal cancer surgery: explorative study. BJS open , 6:zrac072. doi: 10.1093/bjsopen/zrac072 . Sánchez-Guillén, L., Frasson, M., Pellino, G., Fornés-Ferrer, V., Ramos, J. L., Flor-Lorente, B., García-Granero, Á., Sierra, I. B., Jiménez-Gómez, L. M., Moya-Martínez, A., García-Granero, E., & Anaco Study Group (2020). Nomograms for morbidity and mortality after oncologic colon resection in the enhanced recovery era: results from a multicentric prospective national study. International journal of colorectal disease , 35:2227–2238. doi: 10.1007/s00384-020-03692-x . Frasson, M., Granero-Castro, P., Ramos Rodríguez, J. L., Flor-Lorente, B., Braithwaite, M., Martí Martínez, E., Álvarez Pérez, J. A., Codina Cazador, A., Espí, A., Garcia-Granero, E., & ANACO Study Group (2016). Risk factors for anastomotic leak and postoperative morbidity and mortality after elective right colectomy for cancer: results from a prospective, multicentric study of 1102 patients. International journal of colorectal disease , 31:105–14. doi: 10.1007/s00384-015-2376-6 . Zhong, B., Lin, Z. Y., Ma, D. D., Shang, Z. H., Shen, Y. B., Zhang, T., Zhang, J. X., & Jin, W. D. (2022). A preoperative prediction model based on Lymphocyte-C-reactive protein ratio predicts postoperative anastomotic leakage in patients with colorectal carcinoma: a retrospective study. BMC surgery , 22:283. doi: 10.1186/s12893-022-01734-5 . Kroenke, C. H., Neugebauer, R., Meyerhardt, J., Prado, C. M., Weltzien, E., Kwan, M. L., Xiao, J., & Caan, B. J. (2016). Analysis of Body Mass Index and Mortality in Patients With Colorectal Cancer Using Causal Diagrams. JAMA oncology , 2:1137–45. doi: 10.1001/jamaoncol.2016.0732 . Sánchez-Guillén, L., Soriano-Irigaray, L., López-Rodríguez-Arias, F., Barber, X., Murcia, A., Alcaide, M. J., Aranaz-Ostáriz, V., Soler-Silva, Á., Navarro-Ruiz, A., & Arroyo, A. (2021). Effect of Early Peripheral Parenteral Nutrition Support in an Enhanced Recovery Program for Colorectal Cancer Surgery: A Randomized Open Trial. Journal of clinical medicine , 10:3647. doi: 10.3390/jcm10163647 . López-Rodríguez-Arias, F., Sánchez-Guillén, L., Lillo-García, C., Aranaz-Ostáriz, V., Alcaide, M. J., Soler-Silva, Á., Soriano-Irigaray, L., Barber, X., & Arroyo, A. (2021). Assessment of Body Composition as an Indicator of Early Peripheral Parenteral Nutrition Therapy in Patients Undergoing Colorectal Cancer Surgery in an Enhanced Recovery Program. Nutrients , 13:3245. doi: 10.3390/nu13093245 . Cai, W., Calder, P. C., Cury-Boaventura, M. F., De Waele, E., Jakubowski, J., & Zaloga, G. (2018). Biological and Clinical Aspects of an Olive Oil-Based Lipid Emulsion-A Review. Nutrients , 10:776. doi: 10.3390/nu10060776 . Pinzón Espitia, O. L., & Varón Vega, M. L. (2014). Protocolo para el manejo de nutrición parenteral periférica lista para usar en paciente quirúrgico [Protocol for peripheral parenteral nutrition management ready to use in surgical patients]. Nutricion hospitalaria , 31:1003–1011. doi: 10.3305/nh.2015.31.3.8123 . Additional Declarations No competing interests reported. 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. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4325782","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":316389759,"identity":"9cdb4de2-bbc1-4e79-baa8-098aa2df79e7","order_by":0,"name":"Francisco López-Rodríguez-Arias","email":"","orcid":"","institution":"University Miguel Hernández of Elche","correspondingAuthor":false,"prefix":"","firstName":"Francisco","middleName":"","lastName":"López-Rodríguez-Arias","suffix":""},{"id":316389760,"identity":"8ffae6aa-36df-469d-8399-6066062d88e4","order_by":1,"name":"Luis 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Elche","correspondingAuthor":false,"prefix":"","firstName":"Antonio","middleName":"","lastName":"Sanchís-López","suffix":""},{"id":316389762,"identity":"a41dcd15-0bc8-402e-9254-d5fc175e443e","order_by":3,"name":"Verónica Aranaz-Ostáriz","email":"","orcid":"","institution":"Elche University General Hospital, University Miguel Hernández of Elche","correspondingAuthor":false,"prefix":"","firstName":"Verónica","middleName":"","lastName":"Aranaz-Ostáriz","suffix":""},{"id":316389763,"identity":"b3face89-fefb-46cd-9093-33d3f3e0802d","order_by":4,"name":"Ana Sánchez-Romero","email":"","orcid":"","institution":"University Miguel Hernández of Elche","correspondingAuthor":false,"prefix":"","firstName":"Ana","middleName":"","lastName":"Sánchez-Romero","suffix":""},{"id":316389768,"identity":"64571fc2-8ff3-48fd-91b5-75bc3f4646ea","order_by":5,"name":"Maria José Alcaide","email":"","orcid":"","institution":"University Miguel Hernández of Elche","correspondingAuthor":false,"prefix":"","firstName":"Maria","middleName":"José","lastName":"Alcaide","suffix":""},{"id":316389771,"identity":"8a323425-f17c-4728-8fe1-60314acbcde5","order_by":6,"name":"Álvaro Soler-Silva","email":"","orcid":"","institution":"University Miguel Hernández of Elche","correspondingAuthor":false,"prefix":"","firstName":"Álvaro","middleName":"","lastName":"Soler-Silva","suffix":""},{"id":316389773,"identity":"c781490c-c0cc-4234-ab77-31b6c9c56687","order_by":7,"name":"Francisco Javier Lacueva","email":"","orcid":"","institution":"Elche University General Hospital, University Miguel Hernández of Elche","correspondingAuthor":false,"prefix":"","firstName":"Francisco","middleName":"Javier","lastName":"Lacueva","suffix":""},{"id":316389779,"identity":"394131fe-1c18-4a30-ad90-792f4bba8ac8","order_by":8,"name":"Antonio Arroyo","email":"","orcid":"","institution":"University Miguel Hernández of Elche","correspondingAuthor":false,"prefix":"","firstName":"Antonio","middleName":"","lastName":"Arroyo","suffix":""}],"badges":[],"createdAt":"2024-04-25 18:39:59","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4325782/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4325782/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":59291963,"identity":"62180b8a-b9ed-4ab5-bcbb-f0eaae50a289","added_by":"auto","created_at":"2024-06-28 18:50:19","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":80787,"visible":true,"origin":"","legend":"\u003cp\u003eSelection of axial (a) and sagittal (b) slices at the level of the third lumbar vertebra reviewing in yellow the visceral fat area.\u003c/p\u003e","description":"","filename":"Onlinefloatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-4325782/v1/9a3b9ed4eb70aa82c2175b65.png"},{"id":59291962,"identity":"d8f7835d-cb1d-404d-8e3a-8300dbf90189","added_by":"auto","created_at":"2024-06-28 18:50:19","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":12412,"visible":true,"origin":"","legend":"\u003cp\u003eLogistic regression by ROC curve analysis of CRP values prior to surgery and the presence of major anastomotic leakage in the postoperative period.\u003c/p\u003e","description":"","filename":"Onlinefloatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-4325782/v1/bfbbb0022a2d6a7a585ccae6.png"},{"id":59291964,"identity":"89e32c18-c32c-436c-ad3b-eed2264c961e","added_by":"auto","created_at":"2024-06-28 18:50:20","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":23953,"visible":true,"origin":"","legend":"\u003cp\u003eLogistic regression by ROC curve analysis of VFI in males and females and the presence of AL in the postoperative period.\u003c/p\u003e","description":"","filename":"Onlinefloatimage3.png","url":"https://assets-eu.researchsquare.com/files/rs-4325782/v1/ff179dc84420cbd7a3c43542.png"},{"id":62140548,"identity":"ad18a44e-e1af-4f3d-9a6c-137bfc1b19a8","added_by":"auto","created_at":"2024-08-09 17:05:50","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":664327,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4325782/v1/416624d9-1268-48d2-982d-a82472e7c37a.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"\u003cp\u003eConfluence of Preoperative high levels of C-Reactive Protein and Visceral Fat index as Potential Contributor to Postoperative Complications in Colorectal Cancer: a Randomized Clinical Trial Incorporating Parenteral Nutrition\u003c/p\u003e","fulltext":[{"header":"1. INTRODUCTION","content":"\u003cp\u003eColorectal cancer (CRC) is the third most common type of cancer in the world, with an incidence of 19.5 per 100,000 inhabitants, and it is the second leading cause of cancer death in the world, only behind lung cancer\u003csup\u003e1\u003c/sup\u003e. Surgery is still the main pillar of the treatment of CRC, but despite advances in both technological and postoperative management, it continues to present high rates of complications, with the most feared presence being anastomosis leak (AL), with an incidence between 2.5\u0026ndash;33%. Morbidity related with the AL is a determining factor for patient outcome after colorectal surgery and involves many factors related to the underlying disease, hospital setting, surgeon expertise and patient status\u003csup\u003e2\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eTumor growth may trigger a proinflammatory status in some patients that has been related to poor postoperative outcomes and worse oncological prognosis\u003csup\u003e3\u0026ndash;4\u003c/sup\u003e. Therefore, the knowledge of the inflammatory state at the preoperative period would allow initiating an appropriate anti-inflammatory treatment\u003csup\u003e5\u003c/sup\u003e. There is a broad consensus that the evaluation of the systemic inflammatory response with biochemical markers such as C-reactive protein (CRP) will allow us to predict and anticipate postoperative complications in colorectal cancer surgery\u003csup\u003e6\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eMoreover, visceral fat appears to be also associated with increased proinflammatory status of patients\u003csup\u003e7\u003c/sup\u003e favoring a greater inflammatory response after colorectal surgery\u003csup\u003e8\u003c/sup\u003e. CT and magnetic resonance have become the gold standard for measuring the quantitative assessment of visceral fat\u003csup\u003e9\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eVisceral fat has been associated with an increase in postoperative complications \u003csup\u003e10\u003c/sup\u003e and a possible decline in overall survival and disease-free survival as well\u003csup\u003e11\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eIn patients subjected to a surgical stress, which conditions an increase in their catabolism, perioperative parenteral nutrition (PPN) can supplement the intake received orally, reducing mortality and infectious complications\u003csup\u003e12,13\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eThe main outcome of the study was to evaluate the impact of a proinflammatory status measured by means of CRP and the visceral fat index (VFI) of patients undergoing colorectal cancer as a risk factors of AL. In addition, the possible protective effect of PPN of AL occurrence was also assessed as a secondary outcome.\u003c/p\u003e"},{"header":"2. MATERIALS AND METHODS","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003e2.1. Study Design\u003c/h2\u003e \u003cp\u003eAn open, controlled, randomized and one-center superiority clinical trial was conducted to analyze the influence of PPN (PeriOlimel N4-E) versus conventional fluid therapy on AL rates in patients undergoing colorectal surgery based on their proinflammatory status (CRP and VFI). Randomization (1:1) was performed using online randomization software. The investigators, surgeons, patients, and statisticians were unmasked to the group in which the patient was randomly allocated.\u003c/p\u003e \u003cp\u003eBetween October 2016 and September 2019, patients\u0026thinsp;\u0026gt;\u0026thinsp;18 years with nonmetastatic colorectal cancer T1-3Nx were selected for inclusion and intervened by members of the Coloproctology Unit following ERAS protocols.\u003c/p\u003e \u003cp\u003e The study was conducted according to the Helsinki Declaration, was approved by the ethical committee for clinical research of the hospital and was recorded in Clinical Trials (NCT03606863). All patients were invited to participate and signed an informed consent statement before starting the study.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003e2.2. Patients\u003c/h2\u003e \u003cp\u003ePatients at severe nutrition risk (weight loss\u0026thinsp;\u0026gt;\u0026thinsp;10\u0026ndash;15% within 6 months, BMI\u0026thinsp;\u0026lt;\u0026thinsp;18.5 kg/m\u003csup\u003e2\u003c/sup\u003e, SGA grade C or NRS\u0026thinsp;\u0026gt;\u0026thinsp;5, and preoperative serum albumin\u0026thinsp;\u0026lt;\u0026thinsp;30 g/L without evidence of liver or kidney dysfunction)\u003csup\u003e14\u003c/sup\u003e, intraoperative diagnosis of carcinomatosis, metastasis, locally advanced (T4) or unresectable tumors were excluded from the study. Other exclusion criteria were emergency surgery, a physical condition IV of the American Society of Anesthesiologists (ASA), kidney failure defined through hemodialysis, liver failure, allergy or sensitivity to egg or soy protein, severe hemorrhagic disorder, congenital abnormality of hyperlipidemia of amino acid metabolism, not accepting or being able to comply with the ERAS protocol and the absence of a CT scan one month before surgery.\u003c/p\u003e \u003cp\u003eIn addition, for the analysis of anastomotic leakage rates, it was decided to exclude excluded those patients who needed to perform a terminal or protective stoma.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003e2.3. Intervention\u003c/h2\u003e \u003cp\u003ePatients were admitted to the hospital the day before surgery, starting three days before an intestinal preparation at home with a low-fiber diet. Hospital pharmacy identified patients who were assigned to the PPN with Peri-Olimel N4-E group that was started one day before surgery and continued for 3 days after surgery. On the other hand, patients assigned to the control group received a standard postoperative FT that was withdrawn when the patient tolerated oral feeding.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003e2.4. ERAS protocol\u003c/h2\u003e \u003cp\u003ePatients were evaluated after diagnosis by a colorectal surgeon who reported the study and explained the hospital\u0026rsquo;s ERAS protocol\u003csup\u003e16\u003c/sup\u003e, emphasizing the importance of early postoperative mobilization.\u003c/p\u003e \u003cp\u003eCarboxymaltose-rich drinks were given 12 hours and 2 hours before surgery, and antibiotic prophylaxis was administered following the policy of our center.\u003c/p\u003e \u003cp\u003eIn the intraoperative period, priority was given to laparoscopic surgery. Goal-directed fluids were administered, and hypothermia, drainage or nasogastric tubes were avoided. Epidural anesthesia (ropivacaine 0.2%) was used only in open procedures. In the postoperative period, opioid-free pain control and prophylactic medication for nausea and vomiting were performed. In addition, oral fluids were administered early in both groups.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003e2.5. Outcomes\u003c/h2\u003e \u003cp\u003eThe main outcomes gathered were preoperative CRP values and VFI. To classify patients according to their inflammatory state, we used the cutoff point for CPR levels of \u0026lt;\u0026thinsp;5 or \u0026ge;\u0026thinsp;5 mg/L obtained by Bert et al.\u003csup\u003e3\u003c/sup\u003e In addition, a ROC curve was performed to estimate the PCR value prior to surgery with a better sensitivity-specificity relationship to predict anastomotic leaks. The cutoff point for the VFI was determined by the 50th percentile of the sample differentiating men and women to classify patients in High or Low.\u003c/p\u003e \u003cp\u003ePostoperative complications were collected using the Clavien‒Dindo classification and divided into minor complications (Clavien‒Dindo I-II), which included low-risk events such as infection of the surgical wound or postoperative ileus, and major complications (Clavien‒Dindo III-IV)\u003csup\u003e15\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eOccurrence of AL was also gathered. AL was defined following the International Study Group of Rectal Cancer as a communication between the intra- and extraluminal compartments owing to a defect in the integrity of the intestinal wall at the anastomosis. Detailed criteria were as follows: 1) apparent discharge of gas/pus/feces from the abdominal or pelvic drain; 2) anastomotic defect confirmed by proctoscopy, CT scan using contrast medium or rectal examination (only for ultralow rectal anastomosis); and 3) AL confirmed during reoperation. Severity grading of AL was defined as no active therapeutic intervention (Grade A), active therapeutic intervention but manageable without reintervention (Grade B) or requiring surgical reintervention (Grade C)\u003csup\u003e16\u003c/sup\u003e. Grades A and B were considered minor AL, and Grade C was considered major AL.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003e2.6. Body composition analysis\u003c/h2\u003e \u003cp\u003ePatients were classified according to their VFI was assessed from axial slices at the L3 vertebra level on the preoperative CT scan. Figure\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e shows the selection with a sagittal CT image of an axial plane in the third lumbar vertebra, highlighting in yellow the visceral fat area. Images were analyzed using NIH image software ImageJ (\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://imagej.nih.gov.ij/\u003c/span\u003e\u003cspan address=\"https://imagej.nih.gov.ij/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e) by using a fat threshold of -190 to -30 HU. VFI was obtained by dividing the visceral fat area (VFA) by the height squared.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003e2.7. Sample Size\u003c/h2\u003e \u003cp\u003eThe sample size was calculated to compare the incidence of postoperative complications between the two groups. With a confidence level of 95% (alpha\u0026thinsp;=\u0026thinsp;0.05), a potency of 80% (beta\u0026thinsp;=\u0026thinsp;0.2), bilateral contrast and assuming a loss of 10%, 85 patients per group were required.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003e2.8. Statistical analysis\u003c/h2\u003e \u003cp\u003eData were collected prospectively by an external researcher. Continuous variables are described as medians and standard deviations, the Levene test was employed to verify homogeneity and were compared using the Mann-Whitney U and Student\u0026rsquo;s t test. Discrete variables were described as frequencies and percentages and were compared with a Chi-square test.\u003c/p\u003e \u003cp\u003eOrdinal logistic regressions were designed to assess the ability to predict VFI and PCR values for AL. OR and 95% confidence intervals (CI 95%) for AL were calculated in the different risk groups. P values\u0026thinsp;\u0026lt;\u0026thinsp;0.05 were considered significant.\u003c/p\u003e \u003cp\u003eData analysis was performed using IBM SPSS Statistics software.\u003c/p\u003e \u003c/div\u003e"},{"header":"3. RESULTS","content":"\u003cp\u003eA total of 170 patients were consecutively allocated for the trial. Fifty-four patients were excluded because they did not meet the previously established criteria: 7 patients for failure following the protocol, 3 for presenting intraoperative metastatic disease, 2 for revocation of consent during the study, 2 for errors in CT image recovery and 40 patients who needed a terminal or protective stoma. Finally, 116 patients were finally randomized; 63 patients received PPN and 53 received conventional FT. Patient\u0026rsquo;s characteristics are detailed in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\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\u003eThe relationship between clinicopathological characteristics and low or high VFI.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\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=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\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\u003eAll, n\u003c/p\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;116\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eLow VFI, n (%)\u003c/p\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;60 (51.7%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eHigh VFI, n (%)\u003c/p\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;56 (48.3%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eP-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\u003c/p\u003e \u003cp\u003e\u0026lt;\u0026thinsp;70 years\u003c/p\u003e \u003cp\u003e\u003cb\u003e\u0026ge;\u003c/b\u003e\u0026thinsp;75 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e53 (45.7%)\u003c/p\u003e \u003cp\u003e63 (54.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e31 (51.7%)\u003c/p\u003e \u003cp\u003e29 (48.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e22 (39.3%)\u003c/p\u003e \u003cp\u003e34 (60.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.181\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSex\u003c/p\u003e \u003cp\u003eMale\u003c/p\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e69 (59.5%)\u003c/p\u003e \u003cp\u003e47 (40.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e37 (61.7%)\u003c/p\u003e \u003cp\u003e23 (38.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e32 (57.1%)\u003c/p\u003e \u003cp\u003e24 (42.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.620\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eASA score\u003c/p\u003e \u003cp\u003eI-II\u003c/p\u003e \u003cp\u003eIII\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e70 (60.3%)\u003c/p\u003e \u003cp\u003e46 (39.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e42 (70%)\u003c/p\u003e \u003cp\u003e18 (30%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e28 (50%)\u003c/p\u003e \u003cp\u003e28 (50%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.028\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePerioperative nutrition\u003c/p\u003e \u003cp\u003eNPP group\u003c/p\u003e \u003cp\u003eFT group\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e63 (54.3%)\u003c/p\u003e \u003cp\u003e53 (45.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e31 (45.6%)\u003c/p\u003e \u003cp\u003e26 (54.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e32 (45.8%)\u003c/p\u003e \u003cp\u003e27 (54.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.99\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePreoperative PCR value, mean (SD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e13.6 (28.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e13.9 (\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e13.2 (23.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.893\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePostoperative complications\u003c/p\u003e \u003cp\u003eNo\u003c/p\u003e \u003cp\u003eMinor (CD I-II)\u003c/p\u003e \u003cp\u003eMajor (CD III-IV)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e78 (67.2%)\u003c/p\u003e \u003cp\u003e21 (22%)\u003c/p\u003e \u003cp\u003e17 (15.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e41 (68.3%)\u003c/p\u003e \u003cp\u003e11 (18.3%)\u003c/p\u003e \u003cp\u003e8 (13.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e37 (66.1%)\u003c/p\u003e \u003cp\u003e10 (17.9%)\u003c/p\u003e \u003cp\u003e9 (16.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.917\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAnastomosis leak\u003c/p\u003e \u003cp\u003eNo\u003c/p\u003e \u003cp\u003eMinor\u003c/p\u003e \u003cp\u003eMajor\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e100 (86.2%)\u003c/p\u003e \u003cp\u003e3 (2.6%)\u003c/p\u003e \u003cp\u003e13 (11.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e55 (91.7%)\u003c/p\u003e \u003cp\u003e0\u003c/p\u003e \u003cp\u003e5 (8.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e45 (81.4%)\u003c/p\u003e \u003cp\u003e3 (5.1%)\u003c/p\u003e \u003cp\u003e8 (13.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.078\u003c/p\u003e \u003cp\u003e0.069\u003c/p\u003e \u003cp\u003e0.31\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLength of hospital stay, mean (SD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8.7 (SD 9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6.8 (4.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e10.7 (11.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.02\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e \u003cp\u003eSD: Standard deviation, CD: Clavien Dindo, ASA: American Society of Anesthesiologists, VFI: Visceral Fat Index. FT: Fluid Therapy, PPN: Peripheral parenteral nutrition\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003e3.1. Vascular fat index\u003c/h2\u003e \u003cp\u003ePatients were classified as having Low VFI or High VFI according to the median values. High VFI was defined for males as \u0026gt;\u0026thinsp;87.22 cm\u003csup\u003e2\u003c/sup\u003em\u003csup\u003e2\u003c/sup\u003e and for females as \u0026gt;\u0026thinsp;71.66 cm\u003csup\u003e2\u003c/sup\u003em\u003csup\u003e2\u003c/sup\u003e and Low VFI was defined for males as \u0026le;\u0026thinsp;87.22 cm\u003csup\u003e2\u003c/sup\u003em\u003csup\u003e2\u003c/sup\u003e and for females as \u0026le;\u0026thinsp;71.66 cm\u003csup\u003e2\u003c/sup\u003em\u003csup\u003e2\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eThe FT and PPN groups showed a similar distribution depending on the VFI. Patients with a high VFI had a higher rate of major and minor AL (18.7% high VFI vs. 8.3% low VFI; p\u0026thinsp;=\u0026thinsp;0.12) and a longer length of hospital stay (10.7 high VFI vs. 6.8 low VFI; p\u0026thinsp;=\u0026thinsp;0.02).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003e3.2. C- reactive protein\u003c/h2\u003e \u003cp\u003eAssociation between preoperative and postoperative CRP values and VFI are detailed in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e. Preoperative CRP mean values were not different between VFI groups. However, postoperative mean CRP values were higher in High VFI group, especially on the 2nd postoperative day (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05).\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\u003eThe relationship between VFI and CRP values on the day prior to surgery and the first three postoperative days.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\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=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePCR (mg/L)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAll, n\u003c/p\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;116\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eLow VFI, n (%)\u003c/p\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;60\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eHigh VFI, n (%)\u003c/p\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;56\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eP-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePOD \u0026minus;\u0026thinsp;1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e13.6 (SD 28.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e13.8 (SD 32.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e13.4 (SD 23.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.93\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePOD\u0026thinsp;+\u0026thinsp;1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e62.2 (SD 49.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e58.5 (SD 37)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e65.8 (SD 53)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePOD\u0026thinsp;+\u0026thinsp;2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e104.48 (SD 75.39)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e86.12 (SD 64.63)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e117.78 (SD 82.71)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.05\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePOD\u0026thinsp;+\u0026thinsp;3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e96.3 (SD 81.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e91.08 (SD 84.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e101.3 (SD 79.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.5\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e \u003cp\u003eSD: Standard deviation, VFI: Visceral Fat Index, POD: postoperative day.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eAn ordinal logistic regression was performed with an ROC curve associating CRP values before surgery with the presence of AL that obtained a value under the curve of 0.692 (CI 95%: 0.515\u0026ndash;0.869; p\u0026thinsp;=\u0026thinsp;0.025); (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). The best ratio in our model between sensitivity/1 and specificity was for a CRP value of 10.2 mg/l.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003ePatients with high VFI were more prevalent in the CRP\u0026thinsp;\u0026ge;\u0026thinsp;5 mg/L group (43.3% low VFI vs. 56.7% high VFI; p\u0026thinsp;=\u0026thinsp;0.2) and in the CRP\u0026thinsp;\u0026ge;\u0026thinsp;10.2 mg/L group (40.9% low VFI vs. 59.1% high VFI; p\u0026thinsp;=\u0026thinsp;0.17).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec14\" class=\"Section2\"\u003e \u003ch2\u003e3.3. Anastomotic leak\u003c/h2\u003e \u003cp\u003eAn ordinal logistic regression was performed with an ROC curve that associated VFI of CT prior to surgery with the presence of AL, presenting a low curve area of 0.56. However, when differentiating between men and women, we observed that the area under the curve was higher in women (0.683, CI 95%: 0.472\u0026ndash;0.893; p\u0026thinsp;=\u0026thinsp;0.115) than in men (0.438, CI 95%: 0.197\u0026ndash;0.679;p\u0026thinsp;=\u0026thinsp;0.0.592). Figure\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e shows the models of the ROC curve that differentiate men and women.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eThe risk of AL was established according to VFI and previous PCR values having received PPN or FT. These data are shown in Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e. The different combined risk groups presented an OR (CI 95%) for AL of 1.6 in High VFI (p\u0026thinsp;=\u0026thinsp;0.08), 3.6 in CRP\u0026thinsp;\u0026ge;\u0026thinsp;5 mg/dL (p\u0026thinsp;=\u0026thinsp;0.03), 4.8 in patients with CRP\u0026thinsp;\u0026ge;\u0026thinsp;5 mg/dL and with High VFI (p\u0026thinsp;=\u0026thinsp;0.03), 6.6 in \u0026ge;\u0026thinsp;CRP 10.2 mg/dL and 7.3 in patients with CRP\u0026thinsp;\u0026ge;\u0026thinsp;CRP 10.2 mg/dL and with High VIF.\u003c/p\u003e \u003cp\u003eA lower rate of AL was observed in patients who received PPN than in those who received FT in the different risk groups. This difference was greater as the risk of AL increased, although statistical significance was not reached.\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\u003eAnastomotic leak risk scale based on VFI and previous CRP values and PPN effect.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\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=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003en, %\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003eMajor Leakage\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003ep-value\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eOR (CI 95%)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNo (n, %)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eYes (n, %)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eLow VFI\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e60 (51.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e55 (91.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5 (8.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eHigh VFI\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e56 (48.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e48 (85.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e8 (14.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.08\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.6 (0.5\u0026ndash;5.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eControl group\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4 (14.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2.1 (0.35\u0026ndash;12.5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePN group\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4 (12.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.33 (0.27\u0026ndash;6.5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eCRP\u0026thinsp;\u0026lt;\u0026thinsp;5 mg/l\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e67 (58.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e63 (94%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4 (6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eCRP\u0026thinsp;\u0026ge;\u0026thinsp;5 mg/l\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e48 (41.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e39 (81.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e9 (18.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.03\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e3.6 (1.05\u0026ndash;12.6)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eControl group\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4 (20%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e3.8 (0.62\u0026ndash;22.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePN group\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5 (17.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e3.6 (0.63\u0026ndash;20.11)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eCRP\u0026thinsp;\u0026lt;\u0026thinsp;5 mg/l or Low VFI\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e90 (78.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e84 (93.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6 (6.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eCRP\u0026thinsp;\u0026ge;\u0026thinsp;5 mg/l and High VFI\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e25 (21.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e18 (72%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7 (28%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.003\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e4.8 (1.5\u0026ndash;15.8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eControl group\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3 (30%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e5.6 (0.93\u0026ndash;33.4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePN group\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4 (23.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e4.4 (0.87\u0026ndash;22.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eCRP\u0026thinsp;\u0026lt;\u0026thinsp;10.2 mg/L\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e80 (69.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e76 (95%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4 (5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eCRP\u0026thinsp;\u0026ge;\u0026thinsp;10.2 mg/l\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e35 (30.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e26 (74.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e9 (25.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e6.6 (1.9\u0026ndash;23.1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eControl group\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4 (30.85%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e8.2 (1.3\u0026ndash;52.1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePN group\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5 (22.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e5.7 (1.01\u0026ndash;32.5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eCRP\u0026thinsp;\u0026lt;\u0026thinsp;10.2 mg/L or Low VFI\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e94 (81.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e88 (93.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6 (6.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eCRP\u0026thinsp;\u0026ge;\u0026thinsp;10.2 mg/l and High VFI\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e21 (18.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14 (66.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7 (33.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e7.3 (2.1\u0026ndash;25)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eControl group\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3 (37.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e8.2 (1.3\u0026ndash;52.2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePN group\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4 (30.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e6.9 (1.3\u0026ndash;36.6)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"6\" nameend=\"c6\" namest=\"c1\"\u003e \u003cp\u003eCPR: C-reactive protein, VFI: Visceral Fat Index; PN: Parenteral Nutrition; OR: Odds Ratio; CI: Confidence interval\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"4. DISCUSSION","content":"\u003cp\u003eThe present study showed an increased risk of AL in patients with a preoperative high inflammatory state and visceral fat index after CRC surgery and evaluated the possible protective effect of PPN against the occurrence of AL.\u003c/p\u003e \u003cp\u003eThe presence of increased activation of the systemic inflammatory response has been linked to visceral fat\u003csup\u003e18\u003c/sup\u003e. Our analysis showed no differences in mean CRP values prior to surgery based on VFI, but patients with high VFI were more frequent in the CRP groups\u0026thinsp;\u0026ge;\u0026thinsp;5 mg/dL and \u0026ge;\u0026thinsp;10.2 mg/dL. Himber C et al.\u003csup\u003e8\u003c/sup\u003e showed in their analysis a correlation between CRP values and VFA measured by CT, although this correlation was weak.\u003c/p\u003e \u003cp\u003eIn the postoperative period, we observed a difference in CRP values as a function of VFI, reaching statistical significance on the second day. Okamura A. et al.\u003csup\u003e\u003cem\u003e19\u003c/em\u003e\u003c/sup\u003e reported a similar relationship between CRP values and VFA in postoperative patients undergoing esophagectomy.\u003c/p\u003e \u003cp\u003eVisceral fat has also an important influence on postoperative outcomes\u003csup\u003e20\u003c/sup\u003e. One meta-analysis\u003csup\u003e21\u003c/sup\u003e found a relationship between anastomotic leakage and visceral fat area.\u003c/p\u003e \u003cp\u003eSimilarly, Kuritzkes et al.\u003csup\u003e22\u003c/sup\u003e performed an ROC curve model that linked the VFA of patients with the ability to predict major complications. Its area under the curve was higher than ours (0.66 vs. 0.56). The cutoff point with the best sensitivity/1-specificity ratio was 191 cm2, which presented an OR of 2 to predict major complications. However, they did not differentiate the analysis according to the patient\u0026rsquo;s sex. Females are not expected to have a large amount of visceral fat, although having a greater amount of total fat is located preferably in the subcutaneous cell tissue. In males, however, there is a higher ratio of visceral fat/subcutaneous fat\u003csup\u003e10\u003c/sup\u003e. This feature can justify why our ROC curve model has a greater area under the curve in females (0.683 vs. 0.438).\u003c/p\u003e \u003cp\u003eCRP measurement allowed for early detection of anastomotic leak in colorectal cancer surgery, us to anticipate their treatment by reducing the impact and morbidity caused by them\u003csup\u003e23\u003c/sup\u003e. CRP is the most commonly used biomarker for its ability to anticipate AL after colorectal surgery and is considered the gold standard in postoperative follow-up\u003csup\u003e24\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eThe use of biomarkers of the inflammatory response is also beginning to be used in the preoperative period. AL could be related to an altered inflammatory response, expressed by elevated serological levels of inflammatory markers prior to surgery, such as CRP\u003csup\u003e25\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eThe identification of models predicting postoperative complications or specifically anastomotic leakage is one of the current focuses\u003csup\u003e26,27\u003c/sup\u003e. However, most of them use a large number of variables that make it difficult to implement them in normal clinical practice. The determination of factors related to body composition or to patients' presurgery inflammatory state is beginning to be included in these prediction models\u003csup\u003e28,29\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eThe PPN complementary to the oral route has demonstrated its benefit in reducing mortality and complications in situations of high energy demand\u003csup\u003e12,13\u003c/sup\u003e, enhancing its protective effect in fragile patients or with low muscle mass\u003csup\u003e30,31\u003c/sup\u003e. PeriOlimel N4-E is a peripheral parenteral nutrition (PPN) with a high content of oleic acid, which in addition to allowing supplementation via the oral route, could help reduce oxidative stress and the inflammatory response after surgery\u003csup\u003e32\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eThe current guidelines for clinical practice in surgery advise starting an NP in situations of high risk of malnutrition or after 5 days without achieving a satisfactory oral tolerance and do not individualize the treatment according to muscle reserves or the degree of catabolic response presented by the patient\u003csup\u003e15,33\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eOur analysis shows that the reduction in the rate of anastomosis leakage in patients who have received a complementary PPN is greater in patients with a higher degree of inflammatory activation prior to surgery.\u003c/p\u003e \u003cp\u003eTo the best of our knowledge, this is the first study to analyze the risk of AL in CRC surgery within an ERAS program based on the patient\u0026rsquo;s inflammatory state and visceral fat index and to evaluate the possible protective effect of PPN. As limitations of our study, we mainly highlight the low sample size that prevented reaching significant differences in risk group divisions and being a unicentric study. In addition, our risk model for AL is easy to perform, allowing the detection of at-risk patients and the individualization of treatments.\u003c/p\u003e"},{"header":"5. CONCLUSIONS","content":"\u003cp\u003ePreoperative inflammatory state and body composition of patients should be assessed with enough time previous surgery for its treatment. The measurement of CRP prior to surgery and VFI will allow us to stratify the risk of presenting an AL in the postoperative period. In patients with CRP values before surgery of 5 mg/l and high VFI or with CPR values of 10.2 mg/l, supplement with parenteral nutrition in addition to early oral tolerance should be considered to improve AL rates.\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch2\u003eFunding:\u003c/h2\u003e \u003cp\u003eThis study was funded by an investigator-initiated grant from Baxter SL (Spain) to Antonio Arroyo through FISABIO (Foundation for the Promotion of Healthcare and Biomedical Research of the Autonomous Community of Valencia) in Hospital de Elche (Alicante). The sponsor (Baxter) did not participate in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eAll authors whose names appear on the submission1) made substantial contributions to the conception or design of the work; or the acquisition, analysis, or interpretation of data; or the creation of new software used in the work;2) drafted the work or revised it critically for important intellectual content;3) approved the version to be published; and4) agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eWorld Health Organization. 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Protocolo para el manejo de nutrici\u0026oacute;n parenteral perif\u0026eacute;rica lista para usar en paciente quir\u0026uacute;rgico [Protocol for peripheral parenteral nutrition management ready to use in surgical patients]. \u003cem\u003eNutricion hospitalaria\u003c/em\u003e, 31:1003\u0026ndash;1011. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3305/nh.2015.31.3.8123\u003c/span\u003e\u003cspan address=\"10.3305/nh.2015.31.3.8123\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\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, anastomotic leakage, proinflammatory status, visceral fat, body composition, c-reactive protein, parenteral nutrition","lastPublishedDoi":"10.21203/rs.3.rs-4325782/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4325782/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground: \u003c/strong\u003eVisceral fat and inflammatory conditions are risk factors in patients undergoing colorectal cancer (CRC) surgery. This study was conducted to evaluate the effect of early peripheral parenteral nutrition (PPN) in patients with an elevated inflammatory state and/or an increase in their visceral fat on the anastomotic leak of patients undergoing CRC surgery within an enhanced recovery program.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods: \u003c/strong\u003eA clinical trial was performed in patients undergoing CRC surgery between October 2016 and September 2019. Patients were randomized into two groups: PPN with periOlimel N4-E and conventional fluid therapy (FT). With C-reactive protein (CRP) values prior to surgery and visceral fat analysis of preoperative computer tomography, patients were stratified according to their risk of anastomotic leakage (AL). AL rates was obtained in each risk group differentiating whether they had received PPN or FT.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults: \u003c/strong\u003eA total of\u003cstrong\u003e \u003c/strong\u003e116 patients were analyzed; 63 received PPN and 53 FT. Patients with high visceral fat index (VFI) had higher mean postoperative CRP values, especially on the 2nd postoperative day (p\u0026lt;0.05).\u003c/p\u003e\n\u003cp\u003eCRP values prior to surgery ≥5 mg/L and high VFI were associated with an AL rate of 28% (30% FT group vs. 23.5% PPN group): OR (95% CI) of 4.8 (p=0.003), and CRP values ≥10.2 mg/L showed an AL rate of 25.7% (30.8% FT group vs. 22.7% PPN group): OR (95% CI) of 6.6 (p= 0.001).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions: \u003c/strong\u003eAnalysis of visceral fat and the inflammatory state of patients with CRC allows us to evaluate the risk of anastomotic leakage, and PPN should be considered to improve AL rates.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTrial registration number: \u003c/strong\u003eNCT03606863\u003c/p\u003e","manuscriptTitle":"Confluence of Preoperative high levels of C-Reactive Protein and Visceral Fat index as Potential Contributor to Postoperative Complications in Colorectal Cancer: a Randomized Clinical Trial Incorporating Parenteral Nutrition","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-06-28 18:50:13","doi":"10.21203/rs.3.rs-4325782/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":"7dfb1208-97a0-41f9-a055-cd1e03548f2c","owner":[],"postedDate":"June 28th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-08-09T16:57:45+00:00","versionOfRecord":[],"versionCreatedAt":"2024-06-28 18:50:13","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4325782","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4325782","identity":"rs-4325782","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}