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Evaluation of the inflammatory markers CCL8, CXCL5, and LIF in patients with anastomotic leakage after colorectal cancer surgery.

ABSTRACT: PURPOSE:Anastomotic leakage constitutes a dreaded complication after colorectal surgery, leading to increased morbidity and mortality as well as prolonged hospitalization. Most leakages become clinically apparent about 8 days after surgery; however, early detection is quintessential to reduce complications and to improve patients' outcome. We therefore investigated the significance of specific protein expression profiles as putative biomarkers, indicating anastomotic leakage. METHODS:In this single-center prospective cohort study serum and peritoneal fluid samples-from routinely intraoperatively inserted drainages-of colorectal cancer patients were collected 3 days after colorectal resection. Twenty patients without anastomotic leakage and 18 patients with an anastomotic leakage and without other complications were included. Protein expression of seven inflammatory markers in serum and peritoneal fluid was assessed by multiplex ELISA and correlated with patients' clinical data. RESULTS:Monocyte chemoattractant protein 2 (CCL8/MCP-2), leukemia-inhibiting factor (LIF), and epithelial-derived neutrophil-activating protein (CXCL5/ENA-78) were significantly elevated in peritoneal fluid but not in serum samples from patients subsequently developing anastomotic leakage after colorectal surgery. No expressional differences could be found between grade B and grade C anastomotic leakages. CONCLUSION:Measurement 3 days after surgery revealed altered protein expression patterns of the inflammatory markers CCL8/MCP2, LIF, and CXCL5/ENA-78 in peritoneal fluid from patients developing anastomotic leakage after colorectal surgery. Further studies with a larger patient cohort with inclusion of different variables are needed to evaluate their potential as predictive biomarkers for anastomotic leakage.

SUBMITTER: Klupp F

PROVIDER: S-EPMC7320065 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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Evaluation of the inflammatory markers CCL8, CXCL5, and LIF in patients with anastomotic leakage after colorectal cancer surgery.

Klupp F F Schuler S S Kahlert C C Halama N N Franz C C Mayer P P Schmidt T T Ulrich A A

International journal of colorectal disease 20200419 7

<h4>Purpose</h4>Anastomotic leakage constitutes a dreaded complication after colorectal surgery, leading to increased morbidity and mortality as well as prolonged hospitalization. Most leakages become clinically apparent about 8 days after surgery; however, early detection is quintessential to reduce complications and to improve patients' outcome. We therefore investigated the significance of specific protein expression profiles as putative biomarkers, indicating anastomotic leakage.<h4>Methods< ...[more]

PMID: 32307587

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Project description:BackgroundAnastomotic leakage (AL) is a severe complication after colorectal surgery. This study aimed to investigate a method for the early diagnosis of AL after surgical resection by analysing inflammatory factors (IFs) in peritoneal drainage fluid.MethodsAbdominal drainage fluid of patients with colorectal cancer who underwent resection between April 2017 and April 2018, were prospectively collected in the postoperative interval. Six IFs, including interleukin (IL)-1β, IL-6, IL-10, tumour necrosis factor (TNF)-α, matrix metalloproteinase (MMP)2, and MMP9, in drainage were determined by multiplex immunoassay to investigate AL (in patients undergoing resection and anastomosis) and pelvic collection (in patients undergoing abdominoperineal resection). Sparreboom and colleagues' prediction model was first evaluated for AL/pelvic collection, followed by a new IF-based score system (AScore) that was developed by a least absolute shrinkage and selection operator (LASSO) regression, for the same outcomes. The model performance was tested for the area under the curve (AUC), sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV).ResultsOut of 123 patients eligible, 119 patients were selected, including 12 patients with AL/pelvic collection. Sparreboom and colleagues' prediction model was documented with the best diagnostic efficacy on postoperative day 3 (POD3), with an AUC of 0.77. After optimization, AScore on POD3 increased the AUC to 0.83 and on POD1 showed the best diagnostic efficiency, with an AUC of 0.88. Based on the Youden index, the cut-off value of AScore on POD1 was set as -2.46 to stratify patients into low-risk and high-risk groups for AL/pelvic collection. The model showed 90.0 per cent sensitivity, 69.7 per cent specificity, 98.4 per cent NPV, and 25.0 per cent PPV.ConclusionsThe early determination of IFs in abdominal drainage fluid of patients undergoing colorectal surgery could be useful to predict AL or pelvic collection.

Project description:OBJECTIVE:Near-infrared fluorescence (NIRF) imaging using indocyanine green (ICG) might help reduce anastomotic leakage (AL) after colorectal surgery. This pilot study aims to analyze whether a relation exists between measured fluorescence intensity (FI) and postoperative inflammatory markers of AL, C-reactive protein (CRP), Intestinal fatty-acid binding protein (I-FABP), and calprotectin, to AL, in order to evaluate the potential of FI to objectively predict AL. METHODS:Patients scheduled for anastomotic colorectal cancer surgery were eligible for inclusion in this prospective pilot study. During surgery, at three time points (after bowel devascularization; before actual transection; after completion of anastomosis) a bolus of 0.2 mg/kg ICG was administered intravenously for assessment of bowel perfusion. FI was scored in scale from 1 to 5 based on the operating surgeon's judgment (1?=?no fluorescence visible, 5?=?maximum fluorescent signal). The complete surgical procedure was digitally recorded. These recordings were used to measure FI postoperatively using OsiriX imaging software. Serum CRP, I-FABP, and calprotectin values were determined before surgery and on day 1, 3, and 5 postoperative; furthermore, the occurrence of AL was recorded. RESULTS:Thirty patients (n?=?19 males; mean age 67 years; mean BMI 27.2) undergoing either laparoscopic or robotic anastomotic colorectal surgery were included. Indication for surgery was rectal-(n?=?10), rectosigmoid-(n?=?2), sigmoid-(n?=?10), or more proximal colon carcinomas (n?=?8). Five patients (16.7%) developed AL (n?=?2 (6.6%) grade C according to the definition of the International Study group of Rectal Cancer). In patients with AL, the maximum fluorescence score was given less often (P?=?0.02) and a lower FI compared to background FI was measured at 1st assessment (P?=?0.039). However, no relation between FI and postoperative inflammatory parameters could be found. CONCLUSION:Both subjective and measured FI seem to be related to AL. In this study, no relation between FI and inflammatory serum markers could yet be found.

Project description:BackgroundEarly diagnosis of anastomotic leakage (AL) after esophageal resection is crucial for the successful management of this complication. Inflammatory serological markers are indicators of complications during the postoperative course. The aim of the present study was to evaluate the prognostic value of routine inflammatory markers to predict anastomotic leakage after transthoracic esophageal resection.MethodsData from all consecutive patients undergoing transthoracic esophageal resection between January 2010 and December 2016 were analyzed from a prospective database. Besides clinicodemographic parameters, C-reactive protein, white blood cell count and albumin were analyzed and the Noble/Underwood (NUn) score was calculated to evaluate their predictive value for postoperative anastomotic leakage. Diagnostic accuracy was measured by sensitivity, specificity, and negative and positive predictive values using area under the receiver operator characteristics curve.ResultsOverall, 233 patients with transthoracic esophageal resection were analyzed, 30-day mortality in this group was 3.4%. 57 patients (24.5%) suffered from AL, 176 patients were in the AL negative group. We found significant differences in WBCC, CRP and NUn scores between patients with and without AL, but the analyzed markers did not show an independent relevant prognostic value. For CRP levels below 155 mg/dl from POD3 to POD 7 the negative predictive value for absence of AI was > 80%. Highest diagnostic accuracy was detected for CRP levels on 4th POD with a cut-off value of 145 mg/l reaching negative predictive value of 87%.ConclusionsIn contrast to their prognostic value in other surgical procedures, CRP, WBCC and NUn score cannot be recommended as independent markers for the prediction of anastomotic leakage after transthoracic esophageal resection. CRP is an accurate negative predictive marker and discrimination of AL and no-AL may be helpful for postoperative clinical management. Trial registration The study was approved by the local ethical committee (S635-2013).

Dataset Information

Evaluation of the inflammatory markers CCL8, CXCL5, and LIF in patients with anastomotic leakage after colorectal cancer surgery.

Publications

Evaluation of the inflammatory markers CCL8, CXCL5, and LIF in patients with anastomotic leakage after colorectal cancer surgery.

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