PANDORINA: Drainless Distal Pancreatectomy Decreases Postoperative Leaks, Mordibity

Marc Besselink, MD, MSc, PhD

Credit: Amsterdam UMC

Prophylactic passive abdominal drainage is standard practice after distal pancreatectomy to mitigate the consequences of postoperative pancreatic fistula (POPF), but findings from a recent study suggest a no-drain policy may be the more favorable approach.¹

Results published in The Lancet Gastroenterology & Hepatology showed patients who did not receive a drain demonstrated a non-inferior rate of major morbidity and had reduced detection of grade B or C POPF compared to those who received prophylactic passive drain placement.¹

"We expect that drainless surgery for distal pancreatectomy will now enter the international guidelines and become part of daily practice for pancreatic surgeons across the world," Ward van Bodegraven, researcher at Amsterdam University Medical Center and coordinator of the trial, said in a press release.²

POPF is the most significant complication following distal pancreatectomy and is responsible for prolonged hospital stays, increased costs, and delayed adjuvant treatment in malignant disease. A lack of consensus about its definition and grading has hindered the development of interventions and preventive techniques. Though these concepts are now more understood, approaches to the prevention of POPF remain widely debated, especially in the context of drains.^3,4

To assess the safety of a no-drain policy following distal pancreatectomy, investigators conducted an international, multicenter, open-label, randomized controlled, non-inferiority trial among patients ≥ 18 years of age undergoing open or minimally invasive elective distal pancreatectomy for all indications across 12 centers in the Netherlands and Italy. Patients with an American Society of Anesthesiology (ASA) physical status of 4-5 or WHO performance status of 3-4, added by amendment following the death of a patient with ASA 4 due to a pre-existing cardiac condition, were excluded.¹

In total, 282 patients were randomly assigned in a 1:1 ratio intraoperatively by permuted blocks to either no drain or prophylactic passive drain placement. Randomization was stratified by annual center volume, <40 or ≥40 distal pancreatectomies, and risk of grade B or C POPF, with high-risk defined as a pancreatic duct of > 3 mm in diameter, a pancreatic thickness at the neck of more than 19 mm, or both, based on the Distal Pancreatectomy Fistula Risk Score. Investigators considered all other patients low-risk.¹

The study’s primary outcome was the rate of major morbidity (Clavien–Dindo score ≥III), and grade B or C POPF was assessed as a secondary outcome, grading per the International Study Group for Pancreatic Surgery. Outcomes were assessed up to 90 days postoperatively.¹

Among the cohort (n = 282), 138 patients were assigned to the no-drain group and 144 were assigned to the drain group. However, investigators noted 7 patients in the no-drain group received a drain intraoperatively – as a result, the per-protocol population included 131 patients in the no-drain group and 144 patients in the drain group.¹

Upon analysis, the rate of major morbidity was non-inferior in the no-drain group (15%) compared with the drain group (20%) in the intention-to-treat analysis (risk difference, -4.9 percentage points; 95% CI, -13.8 to 4.0; P_{non-inferiority} = .0022). Similar results were observed in the per-protocol analysis (16% vs 20%; risk difference, -4.1 percentage points; 95% CI, -13.2 to 5.0); P_{non-inferiority} = .0045).¹

Investigators observed grade B or C POPF in 12% of patients in the no-drain group and in 27% of patients in the drain group (risk difference, -15.5 percentage points; 95% CI, -24.5 to -6.5; Pnon-inferiority <.0001) in the intention-to-treat analysis. Additionally, they noted 3 patients in the no-drain group died within 90 days versus none in the drain group, although the cause of death was not considered related to the trial in 2 of these patients. The third death was a patient with an ASA score of 4 who died after sepsis and a watershed cerebral infarction at second admission, leading to multiple organ failure.¹

“This study is expected to close a longstanding debate among surgeons," Marc Besselink, MD, MSc, PhD, professor of surgery at Amsterdam University Medical Center and principal investigator of the study, said in a press release.² "In an era where medicine is increasingly becoming more complex and costly, this study actually shows that omitting an intervention actually improves outcome. Sometimes, less is more.”

References:

1. ^{van Bodegraven EA, Balduzzi A, van Ramshorst TME, et al. Prophylactic abdominal drainage after distal pancreatectomy (PANDORINA): an international, multicentre, open-label, randomised controlled, non-inferiority trial. The Lancet Gastroenterology & Hepatology. https://doi.org/10.1016/S2468-1253(24)00037-2}
2. ^{Amsterdam University Medical Center. Less is more: Not placing a drain improves distal pancreatectomy outcomes. EurekAlert! March 15, 2024. Accessed March 19, 2024. https://www.eurekalert.org/news-releases/1037481}
3. ^{Bassi C, Marchegiani G, Dervenis C, et al. The 2016 update of the International Study Group (ISGPS) definition and grading of postoperative pancreatic fistula: 11 Years After. Surgery. https://doi.org/10.1016/j.surg.2016.11.014}
4. ^{Nahm CB, Connor SJ, Samra JS, Mittal A. Postoperative pancreatic fistula: a review of traditional and emerging concepts. Clin Exp Gastroenterol. 2018;11:105-118. Published 2018 Mar 15. doi:10.2147/CEG.S120217}