Bacterial Translocation Markers as Predictors of Infectious and Inflammatory Complications in Acute Bowel Obstruction

Colorectal Cancer Clinical Trial

Official title:

Prognostic Significance of Bacterial Translocation Markers as Predictors of Infectious and Inflammatory Complications in Acute Mechanical Bowel Obstruction

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05229822
• Other study ID #: BT-ABO
• Status: Active, not recruiting
• Start date: March 1, 2021
• Est. completion date: December 31, 2023

Study information

• Verified date: October 2023
• Source: Karaganda Medical University
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Despite modern approaches to the diagnosis and treatment of acute bowel obstruction (ABO), postoperative mortality ranges from 5 to 32%, and complications occur up 23% of cases. One of the formidable infectious and inflammatory complications of ABO is sepsis. The main component of the development of sepsis in ABO is bacterial translocation (BT). BT is the migration of intestinal bacteria or their products through the intestinal mucosa into the mesenteric lymph nodes and further into normally sterile tissues and organs. Today there are several methods for detecting BT: 1. direct method - the detection of 16s rRNA (ribosomal ribonucleic acid) in mesenteric lymph nodes (MLN); 2. indirect method - the detection of serum lipopolysaccharide-binding protein (LBP) and presepsin (Soluble CD14 subtype or sCD14-ST). The aim of this study is to determine the diagnostic and prognostic significance of bacterial translocation as a predictor of the complications development in patients with malignant and benign acute bowel obstruction by assessing the relationship of biomarkers in the systemic circulation (LBP, sCD14-ST) with the detection of microorganism genes (16s rRNA) in mesenteric lymph nodes.

Description:

For the early diagnosis of infectious and inflammatory complications, it is necessary to study LBP, sCD-14 and 16sRNA as bacterial translocation markers in patients with malignant and benign acute bowel obstruction, as well as in patients after planned surgical intervention for colon tumors. Based on changes in bacterial translocation biomarkers in the blood serum, it's suggested that patients with researched pathology can be stratified according to the risk level of developing infectious and inflammatory complications. The study materials are blood serum and mesenteric lymph nodes (MLN). Venous blood sampling will be performed 1 hour before surgery, 24 and 72 hours after it. Venous blood will be collected in 5 ml vacutainers with a coagulation activator and a serum gel separator. It will be centrifuged for 20 minutes at 1000 x g, after which the gel completely separates the serum from the clot, forming a tight barrier.ELISA Kit for Lipopolysaccharide Binding Protein (LBP, Human) and for Presepsin (sCD14-ST, Human), from Cloud-Clone Corp. will be used to determine any presence of LBP and sCD14-ST. The analysis will be performed according to the manufacturer's instructions for an ELISA EVOLIS robotic system from BioRad. The operating surgeon will perform a MLN sampling in sterile conditions during surgery after resection of the intestine from the mesentery of the gross specimen. MLN will be placed in a sterile tube without any fillers. The DNA will be extracted by the GeneJET Genomic DNA Purification Kit manufactured by Thermo Fisher Scientific, USA, in accordance with the manufacturer's instructions. The 16s rRNA bacteria in MLN will be detected by using real-time PCR and BIO-RAD CFX96 amplifier with 16s rRNA forward and reverse primers (U16SRT-F FACTCCTACGGGAGGGAGGCAGGT and U16SRT-R TATTACCGCGGCTGCTGGGC). During the implementation, the resources of the Collective Use Laboratory of Research Center Non-profit Joint Stock Company (NJSC) "Karaganda Medical University" will be used. This research is funded by the Science Committee of the Ministry of Education and Science of the Republic of Kazakhstan (Grant No. AP09260597).

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 150
• Est. completion date: December 31, 2023
• Est. primary completion date: October 31, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• patients with malignant acute bowel obstruction,
• patients with benign acute bowel obstruction,
• colorectal cancer patients without acute bowel obstruction (planned operations).

Exclusion Criteria:

• age less than 18,
• pregnancy,
• patients with paralytic acute bowel obstruction,
• patients with HIV infection, liver cirrhosis,
• patient with an infectious process due to another pathology.

Related Conditions & MeSH terms

• Colon Tumor
• Colonic Neoplasms
• Colorectal Cancer
• Intestinal Obstruction
• Post-Op Complication
• Postoperative Complications
• Systemic Inflammatory Response Syndrome

Intervention

Diagnostic Test:
• LBP
Determine any presence of LBP in blood serum by ELISA method 1 hour before surgery, 24 and 72 hours after it.
• sCD14-ST
Determine any presence of sCD14-ST in blood serum by ELISA method 1 hour before surgery, 24 and 72 hours after it.
• 16s rRNA
Determine any presence of 16s rRNA in mesenteric lymph nodes by PCR method.

Locations

Country	Name	City	State
Kazakhstan	NJSC Karaganda Medical University	Karaganda

Sponsors (2)

Lead Sponsor	Collaborator
Karaganda Medical University	Ministry of Education and Science, Republic of Kazakhstan

Country where clinical trial is conducted

Kazakhstan, 

References & Publications (19)

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Mussap M, Noto A, Fravega M, Fanos V. Soluble CD14 subtype presepsin (sCD14-ST) and lipopolysaccharide binding protein (LBP) in neonatal sepsis: new clinical and analytical perspectives for two old biomarkers. J Matern Fetal Neonatal Med. 2011 Oct;24 Suppl 2:12-4. doi: 10.3109/14767058.2011.601923. — View Citation

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Shwaartz C, Fields AC, Prigoff JG, Aalberg JJ, Divino CM. Should patients With obstructing colorectal cancer have proximal diversion? Am J Surg. 2017 Apr;213(4):742-747. doi: 10.1016/j.amjsurg.2016.08.005. Epub 2016 Sep 2. — View Citation

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* Note: There are 19 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in number of Participants with Post-operative infectious and inflammatory complications	?ny infectious and inflammatory complications in post-operative period (wound suppuration, anastomotic leak, ?bdominal abscesses, peritonitis, sepsis, etc.)	day 3, day 7, day 10
Secondary	LBP level in serum blood	LBP levels will be compared between groups/ subgroups and in each group/subgroup in dynamic.	1 hour before surgery, 24 hours after surgery, 72 hours after surgery
Secondary	sCD14-ST level in serum blood	sCD14-ST levels will be compared between groups/ subgroups and in each group/subgroup in dynamic.	1 hour before surgery, 24 hours after surgery, 72 hours after surgery
Secondary	16s rRNA in mesenteric lymph nodes	Presence or absence of 16s rRNA in mesenteric lymph nodes will be compared between groups/subgroups.	Once (MLN sampling in sterile conditions during surgery)

External Links

•   Masson S, Caironi P, Fanizza C, Thomae R, Bernasconi R, Noto A, Oggioni R, Pasetti GS, Romero M, Tognoni G, Latini R, Gattinoni L. Circulating presepsin (soluble CD14 subtype) as a marker of host response in patients with severe sepsis or septic shock
•   Mierzchala M, Krzystek-Korpacka M, Gamian A, Durek G. Quantitative indices of dynamics in concentrations of lipopolysaccharide-binding protein (LBP) as prognostic factors in severe sepsis/septic shock patients - Comparison with CRP and procalcitonin /