Pathogenesis of Postoperative Infections and Biomarkers for Early Diagnosis of it

New Studies of the Pathogenesis of Postoperative Infections and Development of Biomarkers for Early Diagnosis of Postoperative Complications

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.

Study Overview

• Status: Recruiting
• Conditions: Infections; Complication of Surgical Procedure
• Intervention / Treatment: Procedure: Major visceral surgery for gastrointestinal cancer

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 Type: Observational
• Enrollment (Estimated): 200

Contacts and Locations

• Study Contact: Name: Augustinas Bausys; Phone Number: 37062214027; Email: augustinas.bausys@nvi.lt

Study Locations

• Lithuania
  • Vilnius, Lithuania
    • Recruiting
    • National Cancer Institute
    • Contact: Augustinas Baušys, MD, PhD; Phone Number: +37062363865; Email: augustinas.bausys@nvi.lt
  • Vilnius, Lithuania
    • Recruiting
    • Vilnius University Hospital Santaros Klinikos
    • Contact: Marius Kryzauskas, MD, PhD; Phone Number: +37062214027; Email: marius.kryzauskas@santa.lt

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Patients scheduled to undergo major abdominal surgery due to the cancer of the esophagus, stomach, pancreas, liver, bile ducts, colon, or rectum due to cancer will be eligible to participate.

Description

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 Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The similarity in composition between the infection site microbiome and the gut/oral microbiome.	0 to 30 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of postoperative infections after major abdominal surgery for gastrointestinal cancer.	Infections diagnosed within 30 days after surgery	0 to 30 days
Incidence of surgical site infections after major abdominal surgery for gastrointestinal cancer.	A surgical site infection (SSI) is an infection in the part of the body where a surgery took place.	0 to 30 days
Major abdominal resection impact on gut microbiome composition.	Baseline and POD6 gut microbiome composition will be compared.	0 to 30 days
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.	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.	0 to 30 days
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.	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.	0 to 30 days
The proportion of patients developing wound infections among those with positive and negative wound cultures at the conclusion of surgery.	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.	0 to 30 days

Collaborators and Investigators

• Sponsor: National Cancer Institute, Lithuania
• Collaborators: Vilnius University Hospital Santaros Klinikos

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2024
• Primary Completion (Estimated): May 30, 2025
• Study Completion (Estimated): May 1, 2029

Study Registration Dates

• First Submitted: July 17, 2024
• First Submitted That Met QC Criteria: July 17, 2024
• First Posted (Actual): July 22, 2024

Study Record Updates

• Last Update Posted (Actual): August 1, 2024
• Last Update Submitted That Met QC Criteria: July 30, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Keywords: biomarkers; gastrointestinal cancer; microbiota; postoperative complications; surgical oncology
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Infections; Communicable Diseases; Postoperative Complications
• Other Study ID Numbers: 1v3

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No