Drainage Fluid Biomarkers and Anastomotic Leakage in Colorectal Surgery. A Monocentric Prospective Observational Study (ALbiomarkers)

Drainage Fluid Biomarkers And Anastomotic Leakage In Colorectal Surgery. A Monocentric Prospective Observational Study

Anastomotic leakage (AL) is one of the most feared intra-abdominal septic complications (IASC) after colorectal surgery. It is defined as the leak of intestinal content due to an anastomotic dehiscence. Incidence ranges from 2% to 20%. AL is usually associated to systemic inflammatory response, even if in some cases the presentation may be subclinical. Therefore, AL is suspected in patients with a strong inflammatory response and can be confirmed by imaging with contrast enhanced computed tomography (CT) scan or water-soluble contrast studies. Nevertheless, imaging has varying sensitivity and specificity and is usually performed once the patient has a clinical evidence, thus potentially delaying the correct timing for surgery. Despite several studies about this topic and the plenty of known risk factors as mentioned above, AL is still not easy to predict. Different tools other than imaging have been studied in order to make diagnosis of AL at an early stage, as the measurement of some biomarkers of inflammation in serum and in drainage fluid.

Biomarkers as white cell blood count (WBC), C-reactive protein (CRP), cytokines (e.g. TNFa, IL-6, IL-1b), markers of ischemia (e.g. lactate) and procalcitonin (PCT) have been used for an early detection of AL and other intra-abdominal septic complications. The primary aim of our study was to assess the role of drainage fluid CRP and lactate-dehydrogenase (LDH) in the early detection of anastomotic leakage.

Study Overview

• Status: Completed
• Conditions: Anastomotic Leakage
• Intervention / Treatment: Procedure: Elective or emergency colorectal surgery for cancer, diverticular disease, inflammatory bowel-disease or reversal of Hartmann's procedure

• Study Type: Observational
• Enrollment (Actual): 207

Contacts and Locations

Study Locations

• Italy
  • Italy - Sicily
    • Palermo, Italy - Sicily, Italy, 90127
      • A.U.O. Azienda Ospedaliera Universitaria Policlinico "P. Giaccone" Palermo - University of Palermo

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients undergoing elective or emergency colorectal surgery for cancer, diverticular disease, inflammatory bowel-disease or reversal of Hartmann's procedure

Description

Inclusion Criteria:

• patients aged >16 y undergoing elective or emergency colorectal surgery for cancer
• patients aged >16 y undergoing elective or emergency colorectal surgery for diverticular disease
• patients aged >16 y undergoing elective or emergency colorectal surgery for inflammatory bowel-disease
• patients aged >16 y undergoing elective or emergency colorectal surgery for reversal of Hartmann's procedure.

Exclusion Criteria:

• patients aged < 16 y undergoing colorectal surgery;
• patients undergoing Hartman's procedure

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Biomarker-group; We considered for the study all patients aged >16 y undergoing elective or emergency colorectal surgery for cancer, diverticular disease, inflammatory bowel-disease or reversal of Hartmann's procedure. Both patients undergoing open and minimally invasive surgery were considered eligible.	Procedure: Elective or emergency colorectal surgery for cancer, diverticular disease, inflammatory bowel-disease or reversal of Hartmann's procedure; We considered all the procedures that required an intestinal anastomosis in colo-rectal surgery

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Measurement of drainage fluid CRP and LDH on postoperative day 3	Our primary endpoint was to assess the role of drainage fluid CRP and LDH on postoperative day 3.	Postoperative day 3

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Measurement of drainage fluid pH	Drainage fluid pH measurements were recorded on postoperative day 3 before drain removal.	Postoperative day 3

Collaborators and Investigators

• Sponsor: University of Palermo
• Investigators: Principal Investigator: Antonino Agrusa, Professor, University of Palermo - Italy

Publications and helpful links

General Publications

• Smith SR, Pockney P, Holmes R, Doig F, Attia J, Holliday E, Carroll R, Draganic B. Biomarkers and anastomotic leakage in colorectal surgery: C-reactive protein trajectory is the gold standard. ANZ J Surg. 2018 May;88(5):440-444. doi: 10.1111/ans.13937. Epub 2017 Mar 17.
• Molinari E, Giuliani T, Andrianello S, Talamini A, Tollini F, Tedesco P, Pirani P, Panzeri F, Sandrini R, Remo A, Laterza E. Drain fluid's pH predicts anastomotic leak in colorectal surgery: results of a prospective analysis of 173 patients. Minerva Chir. 2020 Feb;75(1):30-36. doi: 10.23736/S0026-4733.19.08018-0. Epub 2019 Sep 30.
• Straatman J, Cuesta MA, Tuynman JB, Veenhof AAFA, Bemelman WA, van der Peet DL. C-reactive protein in predicting major postoperative complications are there differences in open and minimally invasive colorectal surgery? Substudy from a randomized clinical trial. Surg Endosc. 2018 Jun;32(6):2877-2885. doi: 10.1007/s00464-017-5996-9. Epub 2017 Dec 27.
• Pedrazzani C, Moro M, Mantovani G, Lazzarini E, Conci S, Ruzzenente A, Lippi G, Guglielmi A. C-reactive protein as early predictor of complications after minimally invasive colorectal resection. J Surg Res. 2017 Apr;210:261-268. doi: 10.1016/j.jss.2016.11.047. Epub 2016 Dec 5.
• Cabellos Olivares M, Labalde Martinez M, Torralba M, Rodriguez Fraile JR, Atance Martinez JC. C-reactive protein as a marker of the surgical stress reduction within an ERAS protocol (Enhanced Recovery After Surgery) in colorectal surgery: A prospective cohort study. J Surg Oncol. 2018 Mar;117(4):717-724. doi: 10.1002/jso.24909. Epub 2018 Jan 22.
• Wright EC, Connolly P, Vella M, Moug S. Peritoneal fluid biomarkers in the detection of colorectal anastomotic leaks: a systematic review. Int J Colorectal Dis. 2017 Jul;32(7):935-945. doi: 10.1007/s00384-017-2799-3. Epub 2017 Apr 12.
• Walker PA, Kunjuraman B, Bartolo DCC. Neutrophil-to-lymphocyte ratio predicts anastomotic dehiscence. ANZ J Surg. 2018 Jan 27. doi: 10.1111/ans.14369. Online ahead of print.
• Reynolds IS, Boland MR, Reilly F, Deasy A, Majeed MH, Deasy J, Burke JP, McNamara DA. C-reactive protein as a predictor of anastomotic leak in the first week after anterior resection for rectal cancer. Colorectal Dis. 2017 Sep;19(9):812-818. doi: 10.1111/codi.13649.

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2018
• Primary Completion (Actual): April 1, 2020
• Study Completion (Actual): April 1, 2020

Study Registration Dates

• First Submitted: April 9, 2021
• First Submitted That Met QC Criteria: April 14, 2021
• First Posted (Actual): April 15, 2021

Study Record Updates

• Last Update Posted (Actual): April 15, 2021
• Last Update Submitted That Met QC Criteria: April 14, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Keywords: Colorectal surgery; Anastomotic leakage; Biomarkers
• Additional Relevant MeSH Terms: Pathologic Processes; Postoperative Complications; Anastomotic Leak
• Other Study ID Numbers: ANASTOMOTICLEAKAGE 01_2021

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED