Pathogenesis of Postoperative Infections and Biomarkers for Early Diagnosis of it

Recruiting

• Conditions: Infections; Complication of Surgical Procedure

• Registration Number: NCT06513598
• Lead Sponsor: National Cancer Institute, Lithuania

Brief Summary

Infections remain a prevalent complication after major abdominal surgery. The common belief that most surgical site infections (SSIs) following elective surgery with modern antiseptic techniques are due to intraoperative contamination is still not confirmed. Therefore, alternative mechanisms for SSI development, such as the Trojan Horse theory-which suggests that pathogens from distant sites like the gastrointestinal tract may cause postoperative infections-should be explored. This study aims to analyze the preoperative microbiome of surgical patients' gut and oral cavities and assess whether microorganisms found there are present at the infection site. Additionally, this study will investigate a panel of biomarkers for predicting postoperative infections.

Detailed Description

Infections remain a significant concern following major abdominal surgery. The prevailing notion that most surgical site infections (SSIs) after elective surgery with modern antiseptic techniques are solely caused by intraoperative contamination remains unconfirmed. Therefore, alternative mechanisms for SSI development, such as the Trojan Horse theory-which suggests that pathogens from distant sites like the gastrointestinal tract may contribute to postoperative infections-require thorough investigation. This longitudinal observational study aims to either support or challenge the Trojan Horse theory.

This study will enroll patients undergoing major abdominal surgery for confirmed or suspected cancer. Biological samples from stool, the oral cavity, and infection sites will be collected for sequencing and microbiome analysis to evaluate the presence of pathogens potentially responsible for postoperative infections originating from the gastrointestinal tract. Additionally, blood samples will be collected to identify predictive biomarkers associated with the development of postoperative infections.

Study Timeline

• Status Verified: 2024-07
• Study Start: 2024-07-01
• Study First Submitted: 2024-07-17
• Study First Submitted QC: 2024-07-17
• Study First Posted: 2024-07-22
• Last Update Submitted: 2024-07-30
• Last Update Posted: 2024-08-01
• Primary Completion: 2025-05-30
• Study Completion: 2029-05-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 200

Inclusion Criteria

1. The patient is scheduled to undergo a major resection-type abdominal surgery due to cancer of the esophagus, stomach, pancreas, liver, bile ducts, colon or rectum.
2. Patient is willing to participate.
3. Age ≥ 18 years.

Exclusion Criteria

1. Pregnancy.
2. Previous surgical resection of the digestive tract, excluding appendectomy and/or cholecystectomy.
3. Anticipated operation with preventive ileostomy.
4. The operation is planned to be performed as a matter of urgency.
5. Antibiotic therapy ≤1 month. before surgery.
6. Chronic inflammatory bowel disease (non-specific ulcerative colitis, Crohn's disease) or radiation or other colitis of origin.
7. During the last year, the patient suffered from Cl. difficile colitis or was Cl. difficile carrier, had salmonellosis or others intestinal infections.
8. During the last year, the patient used (> 3 months) pre-/pro-/(syn)biotics.
9. During the last year, the patient has been taking proton pump inhibitors continuously (> 6 months).

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
The similarity in composition between the infection site microbiome and the gut/oral microbiome.	0 to 30 days

Secondary Outcome Measures

Name	Time	Method
Gut microbiome-based biomarkers for postoperative infections.	0 to 30 days
Intestinal wall permeability and local inflammatory markers (LBP, I-FABP, sCD14, etc.) will be evaluated as a potential biomarkers for postoperative infections.	0 to 30 days	Intestinal wall permeability and local inflammatory markers (LBP, I-FABP, sCD14, etc.) on PODs2, 3 and 4 will be evaluated as potential biomarkers for postoperative infections.
Incidence of postoperative infections after major abdominal surgery for gastrointestinal cancer.	0 to 30 days	Infections diagnosed within 30 days after surgery
Incidence of surgical site infections after major abdominal surgery for gastrointestinal cancer.	0 to 30 days	A surgical site infection (SSI) is an infection in the part of the body where a surgery took place.
Major abdominal resection impact on gut microbiome composition.	0 to 30 days	Baseline and POD6 gut microbiome composition will be compared.
Inflammatory cytokines (IL4; IL2; IP10; IL1β; TNFα; etc.) and pro-inflamatory microRNAs (miRNA-21, miRNA-155, etc.) will be evaluated as a potential biomarkers for postoperative infections.	0 to 30 days	Inflammatory cytokines (IL4; IL2; IP10; IL1β; TNFα; etc.) and pro-inflamatory microRNAs (miRNA-21, miRNA-155, etc.) on PODs2, 3 and 4 will be evaluated as potential biomarkers for postoperative infections.
The proportion of patients developing wound infections among those with positive and negative wound cultures at the conclusion of surgery.	0 to 30 days	Wound swabs will be taken for culture at the end of surgery before closing skin. Proportion of patients developing wound infection among patients with positive and negative culture will be determined.

Trial Locations

Locations (2)

National Cancer Institute; 🇱🇹 Vilnius, Lithuania

Vilnius University hospital Santaros Klinikos; 🇱🇹 Vilnius, Lithuania