Prophylactic Abdominal Drainage vs no Drainage After Distal Pancreatectomy

Study Overview
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Brief Summary
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Postoperative pancreatic fistula (POPF) is a major source of morbidity and mortality after pancreatic resection, especially after distal pancreatectomy (PD). Today, POPF remains one of the main causes of hospital length of stay and healthcare costs. Numerous surgical techniques have been tested to reduce its incidence without success, so the current standard for the management of POPF, and the avoidance of associated complications, is intraoperative drain placement. However, surgically placed drains are not without risk. In recent years many studies, mostly retrospective, have attempted to determine whether omission of prophylactic drainage is associated with increased morbidity. These studies suggest that patients may benefit from not having a drain placed. This evidence challenges standard practice and the debate of whether or not to place a drain after distal pancreatectomy remains open. The investigators designed a prospective multicentre randomised non-inferiority study to determine whether prophylactic intraoperative drainage is associated with a lower morbidity rate after distal pancreatectomy.

Detailed Description
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A prospective, randomised, multicentre, multicentre, randomised non-inferiority study is designed. The aim is to study whether patients who undergo distal pancreatectomy can benefit from the non-placement of a drain in terms of clinically relevant postoperative pancreatic fistula and Clavien-Dindo morbidity greater than or equal to 3. Information will be collected for all patients undergoing distal pancreatectomy surgery at the collaborating centres who, upon invitation, voluntarily agree to participate in the study. Those who have agreed to participate, given written consent and meet the inclusion criteria and none of the exclusion criteria will be randomly assigned to one of the following treatment groups: Control group: patients who, after distal pancreatectomy, in whom abdominal drainage is placed. Intervention group: patients who, after distal pancreatectomy, will be omitted the placement of an abdominal drain. Following the postoperative pancreatic fistula score according to the DISPAIR criteria, patients included in the present study will be stratified according to the preoperative risk of postoperative pancreatic fistula into: extreme, high, moderate and low. The standards of surgical technique to be followed in both open and minimally invasive distal pancreatectomy were agreed by consensus. Each patient will be followed up for 6 months from the time of randomisation (day of surgery).Those responsible for the recruitment and selection of patients for inclusion in the research project belong to the Multidisciplinary Committee of Hepatobiliary and Pancreatic Surgery of each centre. Surgical intervention, postoperative management and perioperative morbidity will be evaluated by the surgeon responsible for the patient. A patient recruitment period of 2 years is estimated. After a follow-up period of 6 months, an analysis of postoperative pancreatic fistula rate, perioperative morbidity, biochemical parameters and quality of life will be performed.

Official Title
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PANDREAS. Prophylactic Abdominal Drainage vs no Drainage After Distal Pancreatectomy: a Multicentre Clinical Trial

Conditions
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Postoperative Pancreatic Fistula, Distal Pancreatectomy, Drainage

Intervention / Treatment
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* Procedure: Avoid surgical drainage


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult patients (over 18 years of age) undergoing elective distal pancreatectomy surgery for any indication, with or without splenectomy, minimally invasive or open. It is not necessary to integrate gender perspective as it is not relevant and there is no influence on the results of POPF or morbidity. Signed informed consent was obtained from each of the patients included in the study. Exclusion criteria Patients undergoing distal pancreatectomy as a secondary procedure Additional liver, gastric or colonic resection Pregnancy Participation in another study History of previous surgery involving the pancreas Patients with American Society of Anaesthesiologists classification 4 Arterial resection other than the splenic artery

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: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: National, randomised, prospective, non-inferiority, multicentre clinical trial.To comparatively evaluate the rate of postoperative pancreatic fistula in patients undergoing distal pancreatectomy in one group with and one group without surgical drainage.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Drainage<br>Patients undergoing distal pancreatectomy with surgical drainage. | |
| Experimental: No drainage<br>Patients undergoing distal pancreatectomy without surgical drainage. | Procedure: Avoid surgical drainage<br>* Patients who undergo distal pancreatectomy, avoid placing a drain.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinically relevant postoperative pancreatic fistula | The investigators define a clinically relevant pancreatic fistula following the 2016 update of the International Study Group (ISGPS) definition. According to this, a Clinically Relevant Postoperative Pancreatic Fistula refers to a grade B or C. Grade B requires a change in the postoperative management; drains are either left in place >3 weeks or repositioned through endoscopic or percutaneous procedures. Grade C postoperative pancreatic fistula refers to those postoperative pancreatic fistula that require reoperation or lead to single or multiple organ failure and/or mortality attributable to the pancreatic fistula. | From first postoperative day until day 30 after surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clavien-Dindo morbidity greater than or equal to 3. | To evaluate postoperative morbidity (Clavien-Dindo 3 or higher complications) in patients who undergo distal pancreatectomy. Comparing between the two groups of patients if there are any differences due to the presence or absence of a drainage. According to the Clavien-Dindo classification: 3 - Requiring surgical, endoscopic or radiological intervention 3a-Intervention under regional/local anesthesia 3b- Intervention under general anesthesia 4 -Life-threatening complication requiring intensive care/intensive care unit management 4a- Single organ dysfunction 4b- Multi-organ dysfunction 5 - Patient demise | From first postoperative day until the ninth month after surgery | 
| Reoperation. | To determine the rates of reoperation 90 days after distal pancreatectomy | From first postoperative day until day 90 after surgery | 
| Percutaneous drainage. | To determine the rates of percutaneous drainage 90 days after distal pancreatectomy. The need for a percutaneous drainage procedure, using an endoscopic or radiological approach, for the treatment of postoperative pancreatic fistula. | From first postoperative day until day 90 after surgery | 
| Abdominal collections | To determine the rate of abdominal collections 90 days after distal pancreatectomy. The investigators define an abdominal collection as a presence of liquid in the abdomen that cause symptoms in the patient, such as fever, and that may require less invasive therapeutic agents and treatment or percutaneous, endoscopic or angiographic interventional procedures. | From first postoperative day until day 90 after surgery | 
| Surgical wound infection. | To determine the rates of surgical site infection after distal pancreatectomy. Surgical site infection (SSI) is classified according to the Center for Disease Control and Prevention definition. | From first postoperative day until day 90 after surgery | 
| Delayed gastric emptying. | To determine rates of delayed gastric emptying after distal pancreatectomy. Delayed gastric emptying represents the inability to return to a standard diet by the end of the first postoperative week and includes prolonged nasogastric intubation of the patient. Three different grades (A, B, and C) are defined based on the impact on the clinical course and on postoperative management, according to the definition by the International Study Group of Pancreatic Surgery (ISGPS). | From first postoperative day until day 90 after surgery | 
| Postoperative bleeding. | According to the definition by the International Study Group of Pancreatic Surgery (ISGPS), postpancreatectomy bleeding is defined by 3 parameters: onset, location, and severity. The onset is either early (< or =24 hours after the end of the index operation) or late (>24 hours). The location is either intraluminal or extraluminal. The severity of bleeding may be either mild or severe. Three different grades of postpancreatectomy hemorrhage (grades A, B, and C) are defined according to the time of onset, site of bleeding, severity, and clinical impact. | From first postoperative day until day 90 after surgery | 
| Blood transfusion. | To determine rates of blood transfusion, measured in red blood cell concentrates after distal pancreatectomy. | From first postoperative day until day 90 after surgery | 
| Length of hospital stay | To determine rates of length of hospital stay after distal pancreatectomy. The length of hospital stay will be measured in days. | From first postoperative day until day 90 after surgery | 
| In-hospital mortality. | To determine rates of in-hospital mortality after distal pancreatectomy. The investigators will collet how many patients die during the hospitalization after surgery. | From first postoperative day after surgery. | 
| Intensive care admission. | To determine rates of intensive care admission 90 days after distal pancreatectomy. The investigators will measure how many patients need an intensive care admission and how long after surgery. | From first postoperative day until day 90 after surgery | 
| Mortality. | To determine rates of mortality 90 days after distal pancreatectomy | From first postoperative day until day 90 after surgery | 
| Readmission. | To determine rates of readmission 90 days after distal pancreatectomy. The investigators will collect how many patients, after surgery, needed for a readmission. | From first postoperative day until day 90 after surgery | 
| To study the role of serum amylase in the development of postoperative pancreatic fistula. | The relevance of some biochemical markers that, in an early stage, can predict the development of postoperative pancreatic fistula has recently been highlighted. The serum amylase will be measured in U/L. | From first postoperative day until the fifth day after surgery | 
| To study the role of amylase production in drainage in the development of postoperative pancreatic fistula. | These data will be analysed on the first, third and fifth postoperative day. Amylase concentration in surgical drainage: The amylase concentration in surgical drainage will be measured on postoperative days 1, 3 and 5 to assess the early diagnostic ability of postoperative pancreatic fistula, of a concentration greater than 2000U/L. Drainage fluid amylase production, U/day (the product of the drainage fluid amylase value U/L and the amount of drainage, mL/day) will also be measured. | From first postoperative day until the fifth day after surgery | 
| To study the role of biochemical parameters C-Reactive Protein in the development of postoperative pancreatic fistula. | C-reactive protein concentration will be performed on postoperative days 1, 3 and 5 to assess the early diagnostic capability of POPF of a CRP concentration greater than 100 mg/L. | From first postoperative day until the fifth day after surgery | 
| To study the role of Neutrophil-Lymphocyte Ratio (NLR) in the development of postoperative pancreatic fistula. | The neutrophil/lymphocyte ratio has been published as a biochemical marker for the development of postoperative pancreatic fistula in duodenopancreatectomy. The investigators propose its analysis as a secondary objective, in order to determine its role as an early biochemical marker of fistula after distal pancreatectomy. Haemogram for calculation of serum leukocyte count will be performed on postoperative days 1, 3 and 5 to assess the early diagnostic capability of postoperative pancreatic fistula of a NLR greater than 8.5 mg/dl on these postoperative days. | From first postoperative day until the fifth day after surgery | 
| To identify subgroups of patients according to their risk for postoperative pancreatic fistula | In order to obtain the best evidence, it is proposed not only to analyse differences in morbidity, but also to stratify patients by risk of postoperative pancreatic fistula after distal pancreatectomy, as it is unclear whether omitting routine drainage in subgroups at high risk of postoperative pancreatic fistula could increase the risk of complications.To stratify patients according to the risk of postoperative pancreatic fistula, the DISPAIR score will be used which takes into account three variables: transection site (neck versus body/tail), pancreatic thickness at the transection site and diabetes. These variables have been previously studied as risk factors associated with postoperative pancreatic fistula. | From first postoperative day until the fifth day after surgery | 
| To analyse the quality of life of patients undergoing distal pancreatectomy | To analyse the quality of life of patients undergoing distal pancreatectomy. Variations in patients' quality of life will be measured using the official European Organization for Research and Treatment of Cancer (EORTC) questionnaires QLQ-C30 (generic quality of life questionnaire for cancer patients) and QLQ-PAN26 (specific quality of life questionnaire for pancreatic cancer patients). Although these questionnaires were developed for cancer patients and pancreatic cancer patients, they are widely used to assess postoperative quality of life after pancreatic surgery. | From first postoperative day until the ninth month after surgery | 
| To examine the relevance of the neutrophil-lymphocyte ratio in the exclusion of postoperative pancreatic fistula after distal pancreatectomy. | To examine the relevance of the neutrophil-lymphocyte ratio in the exclusion of postoperative pancreatic fistula after distal pancreatectomy. | From first postoperative day until the fifth day after surgery | 
| To compare the quality of life of patients who undergo distal pancreatectomy according to the placement or non-placement of an intraoperative drain | To compare the quality of life of patients who undergo distal pancreatectomy according to the placement or non-placement of an intraoperative drain. Variations in patients' quality of life will be measured using the official European Organization for Research and Treatment of Cancer (EORTC). Although this questionnaires were developed for cancer patients and pancreatic cancer patients, they are widely used to assess postoperative quality of life after pancreatic surgery. | From first postoperative day until the ninth month after surgery | 
| To compare the quality of life of patients who undergo distal pancreatectomy according to the placement or non-placement of an intraoperative drain | Variations in patients' quality of life will be measured using the QLQ-C30 (generic quality of life questionnaire for cancer patients).Although this questionnaires were developed for cancer patients and pancreatic cancer patients, they are widely used to assess postoperative quality of life after pancreatic surgery. | From first postoperative day until ninth month after surgery | 
| To compare the quality of life of patients who undergo distal pancreatectomy according to the placement or non-placement of an intraoperative drain | Variations in patients' quality of life will be measured using the QLQ-PAN26 (specific quality of life questionnaire for pancreatic cancer patients).Although this questionnaires were developed for cancer patients and pancreatic cancer patients, they are widely used to assess postoperative quality of life after pancreatic surgery. | From first postoperative day until ninth month after surgery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Postoperative pancreatic fistula, Distal Pancreatectomy, Intraoperative Drainage