Perioperative Immune Function and Clinical Complications in Pancreaduodenectomy

Study Overview
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Brief Summary
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Perioperative immunologic signatures can predict the risk of postoperative complications.

Detailed Description
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OBJECTIVE Establish evidence for perioperative immunologic risk stratification of patient's risk for clinically postoperative inflammatory complications as a basis for future mechanism-based intervention studies. Combining detailed immune assessment from cell-receptors to cell expression, cytokines, and complications with a temporal aspect is innovative and provides highly warranted novel multidimensional immunological insight. METHODS Adult patients scheduled for PD on the suspicion of pancreatic cancer excluding patients receiving immunomodulating treatment 1 month properatively and/or autoimmune diseases. Patients scheduled for simultaneous procedures on major blood vessels, and/or adjacent organs (spleen, liver) are also not included. Inoperable patients, for instance, due to carcinosis, circulatory/ventilatory instability hindering procedure completion and/or concomitant surgery on major blood vessels, spleen, or liver, are excluded post-inclusion and will not be part of the primary analysis. Patients eligible for inclusion will be identified before their appointment at the Gastrosurgical Dept., Rigshospitalet which is the largest DK and North-European center with about 200 PD/yr annually. Primary outcome: Persistent postoperative hypotension, defined as need for vassopressor infussion on the morning after surgery to maintain middle arterial bloodpressure >65 mmHg

Official Title
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Perioperative Immune Function and Clinical Complications in Pancreaduodenectomy

Conditions
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Pancreas Cancer

Intervention / Treatment
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* Diagnostic Test: blood sample


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Scheduled for PD on the suspicion of pancreatic cancer Patients able to follow standardised surgical procedure including TIVA anaesthesia with epidural Exclusion Criteria: Bilirubin >100 µmol/ltr Patients receiving immunomodulating treatment 1 month properatively and/or autoimmune diseases and patients non-cenacerous cystic lessions Patients scheduled for simultaneous procedures on major arterial blood vessels, and/or adjacent organs (spleen, liver) Inoperable patients, for instance, due to carcinosis, circulatory/ventilatory instability hindering procedure completion and/or concomitant surgery on major arterial blood vessels, spleen, or liver, are excluded post-inclusion and will not be part of the primary analysis ongoing treatment with glucocortocoid, anti-tnf-alpha etc. patients diagnosed with rheumatological diseases, IBD or chronic infection (eg. HIV)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Occurrence of persistent postoperative hypotension<br>Patients with need for noradrenaline the morning after surgery to maintain middle arterial blood-pressure (MAP)>65 mmHg, after pancreaticoduodenectomy. | Diagnostic Test: blood sample<br>* Blood samples are collected within 24 hours before the surgical procedure, on postoperative day two and seven. Samples collected are as following: TruCulture, flow cytometry, markers of systemic inflammation (Plasma level of pro- and anti-inflammatory molecules assed by Olink inflammation panel, leucocytes, differential count, hemoglobin, thrombocytes and CRP)<br>|
| No occurrence of persistent postoperative hypotension<br>Patients without need for noradrenaline the morning after surgery to maintain middle arterial blood-pressure (MAP)>65 mmHg, after pancreaticoduodenectomy. | Diagnostic Test: blood sample<br>* Blood samples are collected within 24 hours before the surgical procedure, on postoperative day two and seven. Samples collected are as following: TruCulture, flow cytometry, markers of systemic inflammation (Plasma level of pro- and anti-inflammatory molecules assed by Olink inflammation panel, leucocytes, differential count, hemoglobin, thrombocytes and CRP)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients with persistent postoperative hypotension (<65 mmHg) after surgery | Need for vasopressor infusion (noradrenaline) to maintain middle arterial blood pressure >65 mmHg, the morning after pancreaticoduodenectomy. | 24 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients with infection | Ex. surgical site infection, pneumonia, sepsis, etc, based upon international criteria (eg. center for disease control) | 30 days | 
| Number of patients with occurrence (yes/no) of systemic inflammatory response syndrome (SIRS) at any time during the first 30 days | SIRS defined as two or more of either of the following four criteria: i) temperature <36°C or >38°C, ii) heart rate >90/min., iii) respiratory rate >20/min and/or iv) white blood cell count (WBC) <4x109/L (<4000/mm³), >12x109/L (>12,000/mm³) or ≥10% bands neutrophils. | 30 days | 
| Number of patients with severe clinical intra- and postoperatove complications | Complications assessed by Clavien-Dindo classification and Comprehensive Clinical complication Index (CCI) ( (i.e. anastomotic leakage, reoperation, thrombosis, bleeding, etc.) | 30 days | 
| Number of patients with severe clinical intra- and postoperative complications | Complications assessed by SOFA score including single organ system deviation | 30 days | 
| Number of patients with severe perioperative physiological deviations | Frequency og physiological deviation Monitored by WARD-clinical support system (i.e hypotension, desaturation, tachycardia, etc.). | 30 days | 
| Number of patients with development of delirium after surgery | Development of delirium measured with the 3D-CAM score | 7 days |