Cytokine Response to Abdominal Wall Reconstruction

Официальное название

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

Обзор

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.

Подробное описание

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.

Вмешательства

• Другое Not applicable- observational study
  There are no interventions in this observational study.

Первичные конечные точки

• Determine whether fascial closure tension correlates with systemic and peritoneal fluid cytokine activation. [Срок оценки: Baseline through postoperative day 5]

Вторичные конечные точки (9)

• 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. [Срок оценки: 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. [Срок оценки: Baseline through postoperative day 5]
• Incidence of respiratory compromise [Срок оценки: From surgery through hospital discharge (up to 30 days)]
• Incidence of acute kidney injury [Срок оценки: From surgery through hospital discharge (up to 30 days)]
• Incidence of vasopressor use [Срок оценки: From surgery through hospital discharge (up to 30 days)]
• Incidence of postoperative ileus [Срок оценки: From surgery through hospital discharge (up to 30 days)]
• Incidence of wound complications [Срок оценки: From surgery through hospital discharge (up to 30 days)]
• ICU length of stay [Срок оценки: From surgery through hospital discharge (up to 30 days)]
• Hospital length of stay [Срок оценки: From surgery through hospital discharge (up to 30 days)]

Критерии участия

Критерии включения

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

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Да

Дизайн исследования

Модель наблюдения

Когортное

Центры проведения

США · 1 центр

• Northwestern Memorial Hospital — Chicago

Публикации

• 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. PMID 26135695
• 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. Cytokin PMID 17428673
• 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. PMID 15006565
• 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. PMID 8665188
• 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. PMID 15212338
• 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. PMID 38151578
• 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. PMID 22691844
• 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. PMID 26090761

Идентификаторы

NCT: NCT07422584 · STU00225446

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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