Monitoring of patIents With Microdialysis Following Pancreaticoduodenectomy

Study Overview
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Brief Summary
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A pancreaticoduodenectomy is performed in patient with pancreatic cancer. The most common and serious complication is leakage between the intestine and the remnant pancreas after this procedure. It occurs in 20-30%. The result is often prolonged hospital and ICU stay, reoperations and deaths (3-5%). To detect a leakage early before the patient becomes seriously ill, thereby initiating treatment is therefore very important. By inserting a thin microdialysis catheter near the anastomosis between pancreas and intestine before closure of the abdominal wall, the investigators will analyze substances such as lactic acid, pyruvate, glycerol, etc. and if these substances may reveal anastomosis leakage at an early stage. Observational studies have shown that if a leakage occurs, glycerol concentration in the microdialysate will rise significant after few hours, and changes in lactic acid and pyruvate values will change as a sign of inflammation. The investigators want to conduct a randomized study comparing patients undergoing pancreaticoduodenectomy and using microdialysis in half of the included population.

Detailed Description
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Anastomotic leakage after pancreaticoduodenectomy is a feared complication with substantial mortality and morbidity. Treatment of a postoperative pancreatic fistula can be difficult and management may range from a simple observation with or without percutaneous drainage, to the urgent need for reoperation and management of abdominal sepsis with organ failure and prolonged intensive care. To diagnose a pancreatic fistula may have a delay of several days. The risk of death and severe morbidity raises considerable from a biochemical pancreatic fistula compared to the most serious form, a grade C. Also, the cost of managing a patient with a fistula is 1.3-6 times more than a patient with no complications after PD. Microdialysis is a promising tool in patients who undergoes pancreaticoduodenectomy for early detection of postoperative pancreatic fistula development. The technique may reveal an fistula before severe symptoms occur and before the complication gives the patient serious and life-threatening symptoms. Earlier intervention of the postoperative pancreatic fistula may lead to better prognosis, less reoperations and interventions and shorter stay at the ICU/hospital. By monitoring intraperitoneal metabolites (glycerol, lactate, pyruvate and glucose) close to the pancreaticojejunostomy, signs of a leakage may be discovered in few hours, thereby make it possible for early intervention and prevent developement of serious progression of morbidity. The investigators want to perform a randomized study where half of the patients will receive a microdialysis catheter implanted close to the pancreaticoduodenal anastomosis before closure of the abdomen. At certain timepoints postoperatively microdialysate will be analyzed for glycerol, lactate, pyruvate and glucose and the data will be used in the decisionmaking of diagnosing a pancreatic anastomosis leakage in addition to standard management. The other half of the patients will not receive a microdialysis catheter and the decisionmaking will only be based on standard management (ie. inflammation markers in blood samples, amylase in drainage fluid).

Official Title
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Monitoring of patIents With Microdialysis Following Pancreaticoduodenectomy - a Randomized Controlled Trial. THE MINIMUM STUDY

Conditions
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Pancreatic Cancer, Pancreatic Neoplasms, Biliary Tract Cancer, Duodenal Cancer, Pancreatic Fistula

Intervention / Treatment
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* Procedure: Surgical og radiological intervention, antibiotics


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients must be scheduled for a pancreaticoduodenectomy Subject must be ≥ 18 years Able to give written signed informed consent Investigator's assessment that the patient is able to understand, comply and follow the instructions needed to successfully participate in this trial Exclusion Criteria: Allergic to Voluven® (Fresenius Kabi AS, Halden, Norway) and contrast given during CT scan Another study interfering with current study Pregnant

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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Design Details

Primary Purpose: Diagnostic
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: 2-armed, multicenter, randomized, open label, parallel-group controlled trial (RCT)
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Patient with microdialysis<br>Intervention group - Patients will receive an intraperitoneal microdialysis catheter and will be monitored consecutively by microdialysis. The surgeon is familiar with the current microdialysis results at any time during the study period. The surgeon may intervene based on traditional symptoms and signs plus predetermined values of the microdialysis results. | Procedure: Surgical og radiological intervention, antibiotics<br>* Intervention might be a new drainage catheter, replacement of old drainage catheter, reoperation, somatostatin- and antibiotic administration.<br>|
| No Intervention: Patient without microdialysis<br>The control group - The patients will not receive a microdialysis catheter. The patients are monitored according to current standards of care and the surgeon may intervene based only on traditional symptoms and signs. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total hospital stay | Number of days from end of surgery to hospital discharge (at any hospital) | 30 days after surgery - postoperative day 30 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Length of stay at the primary hospital | Length of stay at the primary hospital and ICU. Number of days from initial operation to primary hospital discharge. | 30 days after surgery - postoperative day 30 | 
| Concentration of Lactate (mM), Pyruvate (microM), Glycerol (microM), Glucose (mM) in microdialysate | Concentration of Lactate, Pyruvate, Glycerol, Glucose in microdialysate in relation to patients with or without anastomosis leakage | 30 days after surgery - postoperative day 30 | 
| Concentration of inflammatory markers in microdialysate | Concentration of inflammatory markers in microdialysate in relation to patients with or without anastomosis leakage | 30 days after surgery - postoperative day 30 | 
| Concentration of inflammatory markers in serum | Concentration of inflammatory markers in serum in relation to patients with or without anastomosis leakage | 30 days after surgery - postoperative day 30 | 
| Patient-reported quality of life questionnaire - total score assessed by the Abdominal surgery Impact scale by summing subscores | Total score - Abdominal surgery Impact scale. The summative scores for the scale range from 18 to 126, with higher scores indicating better quality of life | From inclusion to 90-days after surgery | 
| Patient-reported quality of life questionnaire - subgroup score Physical limitations assessed by the Abdominal surgery Impact scale | Subgroup score Physical limitations - Abdominal surgery Impact scale. The summative scores for the scale range from 3 to 18, with higher scores indicating better physical ability | From inclusion to 90-days after surgery | 
| Patient-reported quality of life questionnaire - subgroup score Functional impairment assessed by the Abdominal surgery Impact scale | Subgroup score Functional impairment - Abdominal surgery Impact scale. The summative scores for the scale range from 3 to 18, with higher scores indicating better functional ability | From inclusion to 90-days after surgery | 
| Patient-reported quality of life questionnaire - subgroup score Pain assessed by the Abdominal surgery Impact scale | Subgroup score Pain - Abdominal surgery Impact scale. The summative scores for the scale range from 3 to 18, with higher scores indicating more pain | From inclusion to 90-days after surgery | 
| Patient-reported quality of life questionnaire - subgroup score Visceral Function assessed by the Abdominal surgery Impact scale | Subgroup score Visceral Function - Abdominal surgery Impact scale. The summative scores for the scale range from 3 to 18, with higher scores indicating more Visceral dysfunction | From inclusion to 90-days after surgery | 
| Patient-reported quality of life questionnaire - subgroup score Sleep assessed by the Abdominal surgery Impact scale | Subgroup score Sleep - Abdominal surgery Impact scale. The summative scores for the scale range from 3 to 18, with higher scores indicating more sleep dysfunction | From inclusion to 90-days after surgery | 
| Patient-reported quality of life questionnaire - subgroup score Psychological function assessed by the Abdominal surgery Impact scale | Subgroup score Psychological function - Abdominal surgery Impact scale. The summative scores for the scale range from 3 to 18, with higher scores indicating more psychological dysfunction | From inclusion to 90-days after surgery | 
| Patient-reported pain questionnaire - total score assessed by the McGill Pain Questionnaire-2 (SF-MPQ-2) | Total score - McGill Pain Questionnaire-2 (SF-MPQ-2). Subgroup score Psychological function - Abdominal surgery Impact scale. The summative scores ranging from 0 to 45, with higher score indicating more pain | From inclusion to 90-days after surgery | 
| Expenses (Euros) per patient used during total hospital stay | Number of Euros used in patient undergoing pancreaticoduodenectomy With or without microdialysis catheter | 30 days after surgery - postoperative day 30 | 
| Daily assessement of microdialysis catheter malfunction during admission at hospital, at an average of 10 days after surgery | Number of catheter which are not functioning | From surgery end to discharge from primary hospital, at an average of 10 days after surgery | 
| Risk factors of postoperative pancreatic fistula at discharge from hospital, at an average 10 days after surgery | Numbers of risk factors of postoperative pancreatic fistula in relation to patients with or without anastomosis leakage | From surgery end to discharge from primary hospital at hospital, at an average of 10 days after surgery | 
| Risk factors of postoperative pancreatic fistula at 30 days after surgery | Numbers of risk factors of postoperative pancreatic fistula in relation to patients with or without anastomosis leakage | From surgery end to 30 days after surgery | 
| Risk factors of postoperative pancreatic fistula at 90 days after surgery | Numbers of risk factors of postoperative pancreatic fistula in relation to patients with or without anastomosis leakage | From surgery end to 90 days after surgery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pancreaticoduodenectomy, Pancreatectomy, Anastomosis, Surgical