Cytokine Response to Abdominal Wall Reconstruction

Pilot Study of Systemic Inflammatory and Transcriptomic Responses in Patients Undergoing Open Retromuscular Ventral Hernia Repair

This is a prospective, observational translational study of patients undergoing major abdominal wall reconstruction with primary fascial closure. The project integrates perioperative cytokine profiling, direct measurement of intra-abdominal pressure, and detailed clinical outcomes to define the biologic and physiologic consequences of high-tension closure.

The study includes three cohorts: 1) Healthy controls (N=5), 2) High-tension fascial closure AWR patients (N=10), 3) Low-tension fascial closure AWR patients (N=10). Fascial closure tension will not be altered for the purpose of the study and will be determined by the operating surgeon as part of routine clinical decision-making.

Study Overview

• Status: Recruiting
• Conditions: Incisional Ventral Hernia
• Intervention / Treatment: Other: Not applicable- observational study

Detailed Description

Major abdominal wall reconstruction (AWR) for large ventral hernias is among the most physiologically demanding procedures performed in general surgery. These patients often have a history of multiple prior abdominal operations, chronically altered abdominal wall mechanics and significant loss of domain. Reduction of visceral contents and abdominal wall reconstruction frequently require high-tension closure, resulting in an abrupt increase in intra-abdominal pressure (IAP) that impairs diaphragmatic excursion, reduces splanchnic perfusion, causes renal venous congestion and induces global physiologic stress. Consequently, these patients face a high risk of postoperative complications including respiratory failure, renal dysfunction, and prolonged intensive care unit (ICU) stays.

A critical gap in AWR research is the lack of characterization of the biologic inflammatory and cytokine responses associated with high-tension abdominal wall closure. This gap stands in contrast to robust evidence from the trauma and critical care literature demonstrating that cytokine activation correlates with injury severity and contributes to organ dysfunction and postoperative morbidity.

Defining the inflammatory and cytokine signaling pathways activated during high-tension closure would provide a framework to inform operative planning and perioperative management, particularly in patients with significant comorbidities who may be less tolerant to postoperative physiologic stress. These insights would enable validation of current techniques and establish the foundation for future interventional trials targeting inflammatory pathways to improve postoperative outcomes. The Digestive Health Institute at Northwestern University is uniquely positioned to support this translational research, bridging surgical physiology, inflammation, and patient outcomes.

The investigators hypothesize that:

1. Major abdominal wall reconstruction induces a trauma-like systemic inflammatory response characterized by elevations in GM-CSF, IFN-Gamma, IL-1, IL-2, IL-5, IL-6, IL-8, and TNF-alpha with a concomitant decrease in the anti-inflammatory cytokines, IL-4 and IL-10.
2. Increased intra-abdominal pressure (IAP) following high-tension closure amplifies cytokine activation and is associated with early postoperative organ dysfunction and increased postoperative complications.

• Study Type: Observational
• Enrollment (Estimated): 25

Contacts and Locations

• Study Contact: Name: Megan Melland-Smith, MD; Phone Number: 312-907-1414; Email: megan.mellandsmith@nm.org
• Study Contact Backup: Name: Nancy Ly, MD; Phone Number: 262-455-1560; Email: nancy.ly@nm.org

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Recruiting
      • Northwestern Memorial Hospital
      • Sub-Investigator: Michael Rosen, MD
      • Contact: Megan Melland-Smith, MD; Phone Number: 312-907-1414; Email: megan.mellandsmith@nm.org
      • Contact: Nancy Ly, MD; Phone Number: 262-455-1560; Email: nancy.ly@nm.org
      • Sub-Investigator: Steven Schwulst, MD

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

Participants will include adult patients undergoing elective major abdominal wall reconstruction at Northwestern Memorial Hospital. Patients with large ventral hernias requiring component separation and anticipated primary fascial closure will be eligible.

Description

Inclusion Criteria:

Surgical Participants

• Adults aged 18 years or older
• Scheduled to undergo open retromuscular ventral hernia repair
• Able to provide written informed consent Healthy Control Participants
• Adults aged 18 years or older
• No known inflammatory, autoimmune, or immunologic disease
• Able to provide written informed consent

Exclusion Criteria:

• Emergent or urgent cases
• Pregnancy
• Chronic systemic steroid use or immunosuppressive therapy
• Active infection at the time of enrollment
• Known autoimmune or inflammatory disease
• End-stage organ failure
• Abdominal surgery within the preceding 60 days

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
High tension group; Massive incisional ventral hernias with loss of domain undergoing open ventral hernia repair with transversus abdominis release with placement of mesh and closure of fascia under high tension.	Other: Not applicable- observational study; There are no interventions in this observational study.
Low tension group; Incisional ventral hernias undergoing open ventral hernia repair with transversus abdominis release with placement of mesh and closure of fascia under low tension.	Other: Not applicable- observational study; There are no interventions in this observational study.
Control; Healthy human subjects

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Determine whether fascial closure tension correlates with systemic and peritoneal fluid cytokine activation.	Blood and peritoneal fluid will be collected at baseline (intra-operative), immediately following fascial closure and on postoperative days 1, 3, and 5. Serum cytokine concentrations of GM-CSF, IFN-gamma, IL-1, IL-2, IL-5, IL-6, IL-8, and TNF-alpha (inflammatory); IL-4 and IL-10 (anti-inflammatory) will be measured via multiplex immunoassays (Luminex). Cytokine area under the curve will also be calculated to allow analysis of total cytokine exposure over time.	Baseline through postoperative day 5

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Differences in peripheral blood mononuclear cells and peritoneal macrophage transcriptomic signatures via bulk RNA sequencing between baseline profiles from healthy control subjects, high-tension and low-tension abdominal wall closures.	Peripheral blood mononuclear cells (PBMCs) and peritoneal macrophages will be isolated at baseline, immediately following fascial closure and on postoperative days 1, 3, and 5. Bulk RNA sequencing will be performed. Differentially expressed genes will be determined and KEGG and GO pathway analyses performed.	Baseline through postoperative day 5
Differences in peak intra-abdominal values, intra-abdominal hypertension grading, abdominal perfusion pressure, plateau pressure between baseline profiles from healthy control subjects, high-tension and low-tension abdominal wall closures.	Intra-abdominal pressure (IAP) will be assessed using bladder pressure measurements, along with plateau pressure and abdominal perfusion pressure (APP) - calculated as mean arterial pressure (MAP) minus IAP. Measurements will be obtained at baseline, POD1, POD3 and POD5. Measures will include peak IAP, and duration of intra-abdominal hypertension (IAH), defined as IAP >12mmHg. Peak serum cytokine levels will be correlated with peak IAP using Spearman correlation and multivariable linear regression.	Baseline through postoperative day 5
Incidence of respiratory compromise	Respiratory compromise defined as failure to wean from mechanical ventilation or development of postoperative pneumonia.	From surgery through hospital discharge (up to 30 days)
Incidence of acute kidney injury	Acute kidney injury defined as increase in serum creatinine to >1.5 times baseline with urine output <0.5 mL/kg/hr for 6 hours.	From surgery through hospital discharge (up to 30 days)
Incidence of vasopressor use	Requirement for vasopressor support postoperatively.	From surgery through hospital discharge (up to 30 days)
Incidence of postoperative ileus	Development of postoperative ileus as documented in the medical record.	From surgery through hospital discharge (up to 30 days)
Incidence of wound complications	Development of surgical site infection or wound dehiscence	From surgery through hospital discharge (up to 30 days)
ICU length of stay	Number of days in the intensive care unit following surgery.	From surgery through hospital discharge (up to 30 days)
Hospital length of stay	Total number of days hospitalized following surgery.	From surgery through hospital discharge (up to 30 days)

Collaborators and Investigators

• Sponsor: Northwestern University
• Investigators: Study Director: Michael Rosen, MD, Northwestern University

Publications and helpful links

General Publications

• Jansson K, Redler B, Truedsson L, Magnuson A, Matthiessen P, Andersson M, Norgren L. Intraperitoneal cytokine response after major surgery: higher postoperative intraperitoneal versus systemic cytokine levels suggest the gastrointestinal tract as the major source of the postoperative inflammatory reaction. Am J Surg. 2004 Mar;187(3):372-7. doi: 10.1016/j.amjsurg.2003.12.019.
• Rettig TC, Verwijmeren L, Dijkstra IM, Boerma D, van de Garde EM, Noordzij PG. Postoperative Interleukin-6 Level and Early Detection of Complications After Elective Major Abdominal Surgery. Ann Surg. 2016 Jun;263(6):1207-12. doi: 10.1097/SLA.0000000000001342.
• Petro CC, Raigani S, Fayezizadeh M, Rowbottom JR, Klick JC, Prabhu AS, Novitsky YW, Rosen MJ. Permissible Intraabdominal Hypertension following Complex Abdominal Wall Reconstruction. Plast Reconstr Surg. 2015 Oct;136(4):868-881. doi: 10.1097/PRS.0000000000001621.
• Blatnik JA, Krpata DM, Pesa NL, Will P, Harth KC, Novitsky YW, Rowbottom JR, Rosen MJ. Predicting severe postoperative respiratory complications following abdominal wall reconstruction. Plast Reconstr Surg. 2012 Oct;130(4):836-841. doi: 10.1097/PRS.0b013e318262f160.
• Dimopoulou I, Armaganidis A, Douka E, Mavrou I, Augustatou C, Kopterides P, Lyberopoulos P, Tzanela M, Orfanos SE, Pelekanou E, Kostopanagiotou G, Macheras A, Giamarellos-Bourboulis EJ. Tumour necrosis factor-alpha (TNFalpha) and interleukin-10 are crucial mediators in post-operative systemic inflammatory response and determine the occurrence of complications after major abdominal surgery. Cytokine. 2007 Jan;37(1):55-61. doi: 10.1016/j.cyto.2007.02.023. Epub 2007 Apr 10.
• Badia JM, Whawell SA, Scott-Coombes DM, Abel PD, Williamson RC, Thompson JN. Peritoneal and systemic cytokine response to laparotomy. Br J Surg. 1996 Mar;83(3):347-8. doi: 10.1002/bjs.1800830316. No abstract available.
• Sido B, Teklote JR, Hartel M, Friess H, Buchler MW. Inflammatory response after abdominal surgery. Best Pract Res Clin Anaesthesiol. 2004 Sep;18(3):439-54. doi: 10.1016/j.bpa.2003.12.006.
• Li R, Ye JJ, Gan L, Zhang M, Sun D, Li Y, Wang T, Chang P. Traumatic inflammatory response: pathophysiological role and clinical value of cytokines. Eur J Trauma Emerg Surg. 2024 Aug;50(4):1313-1330. doi: 10.1007/s00068-023-02388-5. Epub 2023 Dec 27.

Study record dates

Study Major Dates

• Study Start (Actual): February 3, 2026
• Primary Completion (Estimated): February 5, 2027
• Study Completion (Estimated): March 5, 2027

Study Registration Dates

• First Submitted: February 4, 2026
• First Submitted That Met QC Criteria: February 12, 2026
• First Posted (Actual): February 20, 2026

Study Record Updates

• Last Update Posted (Actual): February 20, 2026
• Last Update Submitted That Met QC Criteria: February 12, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Other Study ID Numbers: STU00225446

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Individual participant data will not be shared to researchers not involved in specimen processing, data collection or analysis.

Drug and device information, study documents

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