Clinical and Economic Validation of the ISGPS Definition of PPAP

Study Overview
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Brief Summary
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This prospective validation study aims to investigate the incidence of PPAP after pancreaticoduodenectomy (PD) by applying the ISGPS definition and grading system, to demonstrate its clinical impact by examining associated postoperative outcomes, and to validate its applicability through an economic assessment.

Detailed Description
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The study will be conducted at approximately 37 investigative sites in Europe, Asia, Oceania, and the United States. Only high volume centers for Pancreatic Surgery will be included in the study. All patients scheduled to receive elective pancreaticoduodenectomy (PD Kausch-Whipple or Longmire-Traverso) for all type of pancreatic disease (benign, malignant, or premalignant) will be enrolled. The study duration per subject will be up to 30 days after surgery or all the in-hospital lengths of stay. Preoperative care will follow institutional standards, according to each center involved. Surgical resection and reconstruction will be carried out according to the techniques adopted by each participating center. Both patients undergoing open and minimally invasive surgery can be considered eligible. Postoperative management will follow the institutional standards of each center. Serum amylase (total or the pancreatic isoform) and/or lipase activity will be systematically measured at least on postoperative days (POD) 1 and 2.Serum C-reactive protein (CRP) will be measured according to each institutional policy and reported once assessed from POD 1 to 3. Drain fluid amylase, or lipase activity will be checked according to the Institutional standards of each involved, and the values will be retrieved whether assessed from POD 1 to five. Radiological imaging will be performed in the postoperative course when clinically required, facing patients' clinical worsening, suspicious for abdominal complications.The severity of complications will be assessed according to the Clavien-Dindo (CD) classification system 32 . Readmission will be defined as a new hospital admission after discharge within 30 days from index surgery. Length of hospital stay is calculated from the day of surgery to discharge. Preoperative, intra-operative, and postoperative data will be recorded prospectively. The estimated study duration will be 15 months. Time for data analysis must be considered negligible. Patients' follow-up will last 30 days after surgery to catch any additional morbidity even after discharge from the hospital.

Official Title
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Clinical and Economic Validation of the International Study Group for Pancreatic Surgery (ISGPS) Definition of Postpancreatectomy Acute Pancreatitis (PPAP)

Conditions
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Postoperative Acute Pancreatitis, Pancreaticoduodenectomy, Postoperative Pancreatic Fistula, Postoperative Complications

Intervention / Treatment
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* Diagnostic Test: PPAP diagnosis


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Scheduled for elective PD; Male and females ≥ 18 years; Upfront or after neoadjuvant therapy surgery is allowed; The ability of the subject to understand the character and individual consequences of the clinical trial; Written informed consent. Exclusion Criteria: Patients undergoing emergency surgery; Informed consent withdrawal; Inability to perform the resection for any reason; Total or distal pancreatectomy.

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 |
| --- | --- |
| study population<br>Subgroups based on the ISGPS diagnostic criteria and the grading system of PPAP: Without PPAP or POH: Patients without POH nor imaging consistent with AP. POH: sustained postoperative serum hyperamylasemia neither clinically relevant nor consistent imaging PPAP: requiring the fulfilment of three criteria: POH: sustained serum hyperamylasemia greater than the institutional upper limit of normal persisting on postoperative days 1 and 2; macroscopic radiologic features of AP clinically relevant complications. PPAP severity will be classified into grades B and C, with progressive clinical deterioration. | Diagnostic Test: PPAP diagnosis<br>* Serum amylase (total or the pancreatic isoform) and/or lipase activity will be systematically measured at least on postoperative days 1 and 2. A CT with pancreas protocol iv contrast infusion will be performed in the postoperative course when clinically required, facing patients' clinical worsening, suspicious of abdominal complications.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The incidence of PPAP | The incidence of PPAP after pancreaticoduodenectomy (PD) by applying the ISGPS definition and grading system. | 30 postoperative days | 
| The incidence of unplanned ICU admissions and hospital readmission in the PPAP group compared to the non-PPAP one. | Only an unplanned need for intensive care will be defined as intensive care unit (ICU) stay. Readmission will be defined as a new hospital admission after discharge within 30 days from index surgery. | 30 postoperative days | 
| The difference in length of hospital stay between the PPAP and the non-PPAP group | Length of hospital stay is calculated from the day of surgery to discharge. | up to hospital discharge, an average of 30 postoperative days | 
| The difference in hospital costs among the different grades of severity according to the ISGPS grading system22: no PPAP or POH, POH, PPAP grade B, and PPAP grade C groups. | Total hospital costs will comprise the cost of the index admission and every surgery-related readmission within 30 days from the index surgery. Costs will be inflation-adjusted using the standardized national consumer price index and normalized to adjust the variability inherent to different health systems and institutions. | 30 postoperative days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Correlation between postoperative serum amylase/serum lipase activity (U/L) and radiologic feature consistent with PPAP retrieved at postoperative imaging. | Serum amylase and/or lipase activity will be systematically measured on postoperative days (POD) 1 and 2. Radiological imaging will be performed in the postoperative course when clinically required, facing the patient's clinical worsening, and suspicious of abdominal complications. | 30 postoperative days | 
| Incidence and descriptive analysis of radiological features consistent with PAPP at postoperative imaging retrieved at different time points. | The radiologic evaluation will include the pancreas enlargement, pancreas enhancement, pancreatic necrosis and percentage, peripancreatic collections, characteristics, and their location, haemorrhage and pseudoaneurysm, ascites, thrombosis, main pancreatic duct diameter (mm), POD imaging (days). | 30 postoperative days | 
| Incidence and severity of postoperative morbidity. | Postoperative morbidity will be defined according to ISGPS definitions of postoperative pancreatic fistula, delayed gastric emptying, post-pancreatectomy hemorrhage, and chyle leak. Bile leakage as defined by ISGLS. Acute kidney injury will be determined according to 2012 Kidney Disease: Improving Global Outcomes (KDIGO) guidelines. The severity of complications will be assessed according to the Clavien-Dindo classification system. | 30 postoperative days | 
| Incidence of postoperative mortality. | Mortality will be defined as postoperative death recorded out to the point of 30-days postoperatively. Beyond these time limits, the mortality, possibly related to PPAP, will be considered and discussed in each case. | 30 postoperative days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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pancreatitis, hyperamylasemia, pancreatoduodenectomy, postoperative complications, pancreatic fistula