Postoperative drainage after pancreatoduodenectomy: a randomized controlled trial among patients with intermediate and low risks for pancreatic fistula-DRAIN1.

To assess nationwide surgical outcome after pancreatoduodenectomy (PD) in patients at very high risk for postoperative pancreatic fistula (POPF), categorized as ISGPS-D. Morbidity and mortality after ISGPS-D PD is perceived so high that a recent randomized trial advocated prophylactic total pancreatectomy (TP) as alternative aiming to lower this risk. However, current outcomes of ISGPS-D PD remain unknown as large nationwide series are lacking. Nationwide retrospective analysis including consecutive patients undergoing ISGPS-D PD (i.e., soft texture and pancreatic duct ≤3 mm), using the mandatory Dutch Pancreatic Cancer Audit (2014-2021). Primary outcome was in-hospital mortality and secondary outcomes included major morbidity (i.e., Clavien-Dindo grade ≥IIIa) and POPF (ISGPS grade B/C). The use of prophylactic TP to avoid POPF during the study period was assessed. Overall, 1402 patients were included. In-hospital mortality was 4.1% (n=57), which decreased to 3.7% (n=20/536) in the last 2 years. Major morbidity occurred in 642 patients (45.9%) and POPF in 410 (30.0%), which corresponded with failure to rescue in 8.9% (n=57/642). Patients with POPF had increased rates of major morbidity (88.0% vs. 28.3%; P<0.001) and mortality (6.3% vs. 3.5%; P=0.016), compared to patients without POPF. Among 190 patients undergoing TP, prophylactic TP to prevent POPF was performed in 4 (2.1%). This nationwide series found a 4.1% in-hospital mortality after ISGPS-D PD with 45.9% major morbidity, leaving little room for improvement through prophylactic TP. Nevertheless, given the outcomes in 30% of patients who develop POPF, future randomized trials should aim to prevent and mitigate POPF in this high-risk category.

This meta-analysis compares outcomes of pancreaticoduodenectomy (PD) using open (OPD), robotic (RPD), and laparoscopic (LPD) techniques in patients with and without obesity and resectable pancreatic cancer. Thirteen observational studies evaluating 30-day mortality and postoperative complications in patients that underwent PD were included. Outcomes included mortality, major complications (Clavien-Dindo classification), and specific surgical complications: postoperative pancreatic fistula (POPF), post-PD hemorrhage (PPH), delayed gastric emptying (DGE), and surgical site infections (SSI). Patients with obesity had higher 30-day mortality rates (2.42% vs. 1.63%; OR: 1.68, 95% CI: 1.35-2.08, p < 0.00001, I² = 0%) and major complications (23.3% vs. 17.12%; OR: 1.77, 95% CI: 1.27-2.46, p = 0.0007, I² = 52%) than patients without obesity. Obesity also increased the risk of POPF (21.9% vs. 13.76%; OR: 2.04, 95% CI: 1.69-2.46, p < 0.00001, I² = 26%), PPH (7.31% vs. 6.26%; OR: 1.44, 95% CI: 1.07-1.94, p = 0.02, I² = 0%), and DGE (20.23% vs. 15.5%; OR: 1.98, 95% CI: 1.3-3.03, p < 0.00001, I² = 89%). SSI risk trended higher in patients with obesity but was not statistically significant (28.17% vs. 20.39%; OR: 1.80, 95% CI: 0.93-3.5, p = 0.08, I² = 90%). Among surgical techniques, patients with obesity who underwent OPD had higher risks of 30-day mortality (OR: 1.59, 95% CI: 1.26-2.00, p < .0001), major complications (OR 1.63, 95% CI 1.17-2.28, p = 0.004), and POPF (OR 1.98, 95% CI 1.59-2.47, p < 0.00001) than patients without obesity. In the RPD group, obesity increased the risk of 30-day mortality (OR: 2.68, 95% CI: 1.12-6.39, p = 0.03) and POPF (OR 3.32, 95% CI 1.68-6.57, p = 0.0006). In LPD, obesity was associated with a higher risk of POPF (OR 2.06, 95%CI 1.69-3.32, p = 0.003). Patients with obesity undergoing PD are at increased risk for 30-day mortality and major complications. OPD carries the highest overall risk, while RPD and LPD are linked to a greater POPF risk. These findings highlight the need for careful perioperative management in this high-risk population.

Objective: To study the preoperative computed tomography (CT) data of patients with pancreaticoduodenectomy (PD) and to explore the effective of predicting the risk of postoperative pancreatic fistula (POPF). Methods: CT images of patients with PD were analyzed retrospectively from June 2010 to January 2017 in Zhengzhou University of People's Hospital. The pancreas index, pancreatic duct width, pancreas CT value, pancreas-spleen CT value, and pancreas thickness were collected. The relationship between the indicators and the POPF was determined, and the receiver operation characteristic (ROC) curve was calculated and the area under the curve (AUC) was evaluated. The maximum predictive performance of the critical value was determined by using the different cut-off values to calculate the Youden index and other indicators. Results: A total of 154 patients with PD were involved in the study and 27 (17.5%) had POPF. Seven indicators were significantly associated with POPF. The pancreas index had the largest AUC (AUC: 0.865, P<0.001) and pancreatic duct width (AUC: 0.834, P<0.001) also had a higher predictive value. The pancreatic duct (P<0.001) was significantly associated with POPF. Pancreas thickness, pancreas and spleen CT ratio, abdominal wall fat thickness, pancreas CT value, pancreatic abdominal aorta CT ratio and POPF were also related. Using 0.15 as the cut-off value, the sensitivity, specificity, Jordan index, and accuracy of pancreatic index were 83%, 86%, 0.69, and 0.88 respectively, with the highest performance prediction. Abdominal circumference, spleen CT value and other six indicators had no correlation with POPF. Conclusion: Analysis of preoperative CT indicators of patients can predict the risk of POPF in patients after PD. The pancreas index has the greatest predictive efficacy, while pancreatic duct width, pancreatic spleen density ratio and other indicators also associated with POPF.

Preoperative Risk Stratification of Postoperative Pancreatic Fistula: Training and External Validation of a Risk-tree Predictive Model for Pancreatoduodenectomy

Introduction. The study investigates the prognostic significance of preoperative computed tomography (CT) parameters, particularly pancreatic parenchymal density and duct-to-parenchyma (D/P) ratio, in predicting the risk of postoperative pancreatic fistula (POPF) following pancreatoduodenectomy (PD). POPF remains a major postoperative complication, with incidences between 6–60%, prolonging hospital stays and escalating treatment costs. This research addresses the limitations of subjective intraoperative assessments, proposing objective, preoperative CT-based criteria to forecast POPF risk. Methods. A prospective study was conducted with 234 patients undergoing PD between January 2022 and November 2023. The research employed multiphase contrast-enhanced CT imaging to assess pancreatic density (in Hounsfield Units, HU) and D/P ratio at the expected resection site above the superior mesenteric vein. Density was measured using unenhanced CT, while D/P ratios were calculated based on duct and parenchymal measurements in two planes. The radiologists were blinded to patient outcomes, and logistic regression models were utilized to assess the prognostic value of these metrics. Results. The study identified a significant association between lower pancreatic density and increased POPF risk. Patients with POPF had a median density of 22 HU compared to 39.65 HU in patients without POPF. Similarly, lower ventrodorsal and craniocaudal D/P ratios correlated with higher POPF incidence. Logistic regression models demonstrated that low pancreatic density and D/P ratio are independent predictors of POPF, with an area under the ROC curve (AUC) of 0.91 for pancreatic density and 0.86 for the D/P ratio. A combined model achieved the highest prognostic accuracy (AUC = 0.92), suggesting these parameters are valuable for preoperative POPF risk stratification. Conclusions The study concludes that low pancreatic density and a low D/P ratio, identified through preoperative CT planimetry, are reliable predictors of POPF following PD. These parameters enable a more objective risk assessment, potentially guiding individualized surgical strategies to mitigate POPF risk. Future studies with larger cohorts are warranted to validate these findings and explore histological correlations.

Following pancreatoduodenectomy (PD), the modality of pancreato-enteric continuity restoration may impact on postoperative pancreatic fistula (POPF) risk. The aim of this study is to compare, among patients with soft pancreas and at moderate/high risk for POPF, the outcomes of PD with Pancreato-Gastrostomy (PG), versus Isolated Jejunal Loop Pancreato-Jejunostomy (IJL-PJ). 193 patients with a Callery Fistula Risk Score (C-FRS) ≥ 3 operated at 3 HPB Units, two performing PG and one IJL-PJ as their preferred anastomotic technique following PD (2009-2019) were included in this study (PG = 123, IJL-PJ = 70). Primary outcomes were POPF, clinically relevant (cr-)postoperative pancreatic hemorrhage (cr-PPH), delayed gastric emptying (cr-DGE), and postoperative major complications and mortality. POPF, cr-PPH, and cr-DGE occurred in 21.8%, 17.6%, and 11.4% of patients, and did not differ significantly between PG (26%, 19.5%, and 10.6%, respectively) and IJL-PJ (17.1%, 14.3%, and 12.9%, respectively; all p > 0.05) patients. Major (Dindo ≥ 3) complication and mortality rates were 26.4% and 3.3%, respectively, and did not differ significantly between PG (29.3% and 3.8%) and IJL-PJ (21.4% and 2.9) patients (p > 0.05). A faster surgical drain and nasogastric tube removal matched a significantly shorter hospitalization among IJL-PJ patients (median LOS: 18days versus 25days among PG patients, p < 0.001). In conclusion, IJL-PJ and PG, when performed by surgeons specialized with the concerned anastomotic technique in patients with soft pancreas and moderate/high risk for POPF, have similar results in terms of perioperative mortality and postoperative complications both overall and specific for PD.

To compare the short-term outcomes of pancreaticojejunostomy (PJ) and pancreatic duct occlusion (PDO) in patients at intermediate-high risk of postoperative pancreatic fistula (POPF). Postoperative pancreatic fistula (POPF) is the most fearsome complication of pancreaticoduodenectomy (PD). Patients undergoing PD with intermediate-high fistula risk scores (FRS) at two tertiary centers between 2012 and 2022 were included. To reduce biases between the groups, entropy balance and inverse probability of treatment weighting (EB-IPTW) were used. A total of 302 patients were included (224, 74.2% PJs and 78, 25.8% PDOs). After EB-IPTW, two weighted pseudo-populations of 224 patients were obtained. Major complications, POPF, reoperations and post-operative mortality were similar. Patients undergoing PDO had lower rates of grade C POPF (3.3% vs. 6.7%), delayed gastric emptying (15.7% vs. 24.6%, P=0.02), intra-abdominal collections (7.3% vs. 20.5%, P<0.001) and 90-day readmissions (2.7% vs. 9.4%, P=0.005). In subgroup analysis, PDO reduced POPF in patients with high FRS and blood loss >400mL, while PJ was more effective in intermediate FRS class, duct diameter ≥2mm, blood loss <400mL, ASA class >II, younger patients and BMI <25kg/m2. In the unbalanced cohorts, completion pancreatectomy was required in 10 (4.5%) patients after PJ and in 1 (1.2%) after PDO. The main perioperative outcomes of PJ and PDO after PD in intermediate-high risk FRS patients are similar. PDO decreases the rate of POPF in patients with high-risk FRS, and reduces the need of completion pancreatectomy in case of reoperation.

The incidence of postoperative pancreatic fistula following distal pancreatectomy is as high as 30%-50%. Postoperative pancreatic fistula can be a major cause of perioperative morbidity, resulting in prolonged hospital stays and increased health care costs. The management of the pancreatic stump is one of the key factors influencing the occurrence of postoperative pancreatic fistula after distal pancreatectomy, but the optimal management approach remains debatable. The main methods for pancreatic stump closure include manual suturing and stapler closure. However, both methods are associated with a high risk of postoperative pancreatic fistula, which may be related to the balance between providing sufficient pancreatic duct burst pressure and ensuring blood supply to the stump. Ligation of the pancreatic stump has been attempted to reduce the risk of postoperative pancreatic fistula following distal pancreatectomy, but its efficacy remains limited by the challenge of achieving the optimal ligation force. This study aims to investigate whether ligation of the pancreatic stump with a quantified force can decrease the risk of postoperative pancreatic fistula following distal pancreatectomy. In this nonrandomized controlled clinical study at a tertiary center in China, the major eligibility criterion is the presence of lesions planned for distal pancreatectomy. Sixty patients will be allocated to the experimental or control group according to their choice. Recruitment for either group will be discontinued upon reaching the predefined sample size of 30 participants. In the experimental group, the pancreas will be ligated 5 mm from the pancreatic stump with a quantified force to provide a pancreatic duct burst pressure of approximately 40-70 mm Hg. The ligation force will be provided by a 3.2-mm-diameter silicone ring. During pancreatic stump ligation, this silicone ring will be stretched to 15 mm, generating an applied force of 1.3 N. The pancreas will be severed using energy-based devices before or after the ligation. In the control group, the pancreatic stump will be managed by manual suturing or stapling closure according to the surgeon's clinical judgment and preference. Postoperative regular follow-up examinations will be conducted. The primary outcomes include postoperative pancreatic fistula and postoperative hospital stay, and the secondary outcomes include intra-abdominal infection, incision infection, and postoperative treatment costs. The primary and secondary outcomes of patients in this cohort will be statistically compared using appropriate tests. This study started in February 2025, and the recruitment period is from February to September 2025. This protocol proposes a novel approach for pancreatic stump management aimed at preventing postoperative pancreatic fistula following distal pancreatectomy. The research team established the optimal ligation force for the pancreatic stump to ensure adequate burst pressure for the pancreatic duct while preventing acute stump necrosis, thereby theoretically reducing the risk of postoperative pancreatic fistula. Chinese Clinical Trial Register ChiCTR2500097781; https://www.chictr.org.cn/showproj.html?proj=247008. DERR1-10.2196/74018.

To assess the learning curve of pancreaticojejunostomy during robotic pancreatoduodenectomy (RPD) and to predict the risk of postoperative pancreatic fistula (POPF) by using the objective structured assessment of technical skills (OSATS), taking the fistula risk into account. RPD is a challenging procedure that requires extensive training and confirmation of adequate surgical performance. Video grading, modified for RPD, of the pancreatic anastomosis could assess the learning curve of RPD and predict the risk of POPF. Post hoc assessment of patients prospectively included in 4 Dutch centers in a nationwide LAELAPS-3 training program for RPD. Video grading of the pancreaticojejunostomy was performed by 2 graders using OSATS (attainable score: 12-60). The main outcomes were the combined OSATS of the 2 graders and POPF (grade B/C). Cumulative sum analyzed a turning point in the learning curve for surgical skill. Logistic regression determined the cutoff for OSATS. Patients were categorized for POPF risk (ie, low, intermediate, and high) based on the updated alternative fistula risk scores. Videos from 153 pancreatic anastomoses were included. Median OSATS score was 48 (interquartile range: 41-52) points and with a turning point at 33 procedures. POPF occurred in 39 patients (25.5%). An OSATS score below 49, present in 77 patients (50.3%), was associated with an increased risk of POPF (odds ratio: 4.01, P =0.004). The POPF rate was 43.6% with OSATS < 49 versus 15.8% with OSATS ≥49. The updated alternative fistula risk scores category "soft pancreatic texture" was the second strongest prognostic factor of POPF (odds ratio: 3.37, P =0.040). Median cumulative surgical experience was 17 years (interquartile range: 8-21). Video grading of the pancreatic anastomosis in RPD using OSATS identified a learning curve and a reduced risk of POPF in case of better surgical performance. Video grading may provide a valid method to surgical training, quality control, and improvement.

Objective: To assess the learning curve of pancreaticojejunostomy during robotic pancreatoduodenectomy (RPD) and to predict the risk of postoperative pancreatic fistula (POPF) by using the objective structured assessment of technical skills (OSATS), taking the fistula risk into account. Background: RPD is a challenging procedure that requires extensive training and confirmation of adequate surgical performance. Video grading, modified for RPD, of the pancreatic anastomosis could assess the learning curve of RPD and predict the risk of POPF. Methods: Post hoc assessment of patients prospectively included in 4 Dutch centers in a nationwide LAELAPS-3 training program for RPD. Video grading of the pancreaticojejunostomy was performed by 2 graders using OSATS (attainable score: 12-60). The main outcomes were the combined OSATS of the 2 graders and POPF (grade B/C). Cumulative sum analyzed a turning point in the learning curve for surgical skill. Logistic regression determined the cutoff for OSATS. Patients were categorized for POPF risk (ie, low, intermediate, and high) based on the updated alternative fistula risk scores. Results: Videos from 153 pancreatic anastomoses were included. Median OSATS score was 48 (interquartile range: 41-52) points and with a turning point at 33 procedures. POPF occurred in 39 patients (25.5%). An OSATS score below 49, present in 77 patients (50.3%), was associated with an increased risk of POPF (odds ratio: 4.01, P = 0.004). The POPF rate was 43.6% with OSATS < 49 versus 15.8% with OSATS ≥ 49. The updated alternative fistula risk scores category "soft pancreatic texture" was the second strongest prognostic factor of POPF (odds ratio: 3.37, P = 0.040). Median cumulative surgical experience was 17 years (interquartile range: 8-21). Conclusions: Video grading of the pancreatic anastomosis in RPD using OSATS identified a learning curve and a reduced risk of POPF in case of better surgical performance. Video grading may provide a valid method to surgical training, quality control, and improvement.

BackgroundPostoperative pancreatic fistula remains the leading cause of significant morbidity after pancreatoduodenectomy for pancreatic ductal adenocarcinoma. Preoperative chemoradiotherapy has been described to reduce the risk of postoperative pancreatic fistula, but randomized trials on neoadjuvant treatment in pancreatic ductal adenocarcinoma focus increasingly on preoperative chemotherapy rather than preoperative chemoradiotherapy. This study aimed to investigate the impact of preoperative chemotherapy and preoperative chemoradiotherapy on postoperative pancreatic fistula and other pancreatic-specific surgery related complications on a nationwide level. MethodsAll patients after pancreatoduodenectomy for pancreatic ductal adenocarcinoma were included in the mandatory nationwide prospective Dutch Pancreatic Cancer Audit (2014–2020). Baseline and treatment characteristics were compared between immediate surgery, preoperative chemotherapy, and preoperative chemoradiotherapy. The relationship between preoperative chemotherapy, chemoradiotherapy, and clinically relevant postoperative pancreatic fistula (International Study Group of Pancreatic Surgery grade B/C) was investigated using multivariable logistic regression analyses. ResultsOverall, 2,019 patients after pancreatoduodenectomy for pancreatic ductal adenocarcinoma were included, of whom 1,678 underwent immediate surgery (83.1%), 192 (9.5%) received preoperative chemotherapy, and 149 (7.4%) received preoperative chemoradiotherapy. Postoperative pancreatic fistula occurred in 8.3% of patients after immediate surgery, 4.2% after preoperative chemotherapy, and 2.0% after preoperative chemoradiotherapy (P = .004). In multivariable analysis, the use of preoperative chemoradiotherapy was associated with reduced risk of postoperative pancreatic fistula (odds ratio, 0.21; 95% confidence interval, 0.03–0.69; P = .033) compared with immediate surgery, whereas preoperative chemotherapy was not (odds ratio, 0.59; 95% confidence interval, 0.25–1.25; P = .199). Intraoperatively hard, or fibrotic pancreatic texture was most frequently observed after preoperative chemoradiotherapy (53% immediate surgery, 62% preoperative chemotherapy, 77% preoperative chemoradiotherapy, P < .001). ConclusionThis nationwide analysis demonstrated that in patients undergoing pancreatoduodenectomy for pancreatic ductal adenocarcinoma, only preoperative chemoradiotherapy, but not preoperative chemotherapy, was associated with a reduced risk of postoperative pancreatic fistula.

Drains are frequently placed at the time of distal pancreatectomy (DP) to evacuate pancreatic juice and intra-abdominal exudate and obtain information on abdominal cavity status. However, the timing of drain removal remains debatable. Meanwhile, prolonged drain placement might increase the risk of postoperative pancreatic fistula (POPF), with a prevalence of 5-40%. Therefore, we examined the effect of removing the drain within postoperative day (POD) 3 on the risk of POPF development. A total of 108 consecutive patients who underwent DP between April 2015 and March 2020 were examined and divided into two groups according to the day of drain removal; hence, for some patients, the drain was removed on POD 1 (POD 1 group) and for others on POD 3 (POD 3 group). Furthermore, risk factors, including drain fluid amylase (DFA) levels, for developing POPF were investigated. The overall rate of clinically relevant POPF was 4.6% and did not significantly differ between the POD 1 and POD 3 groups [4.5% and 4.9%, respectively (p=0.924)]. DFA levels on POD 1 did not significantly differ between patients with and without POPF. On POD 3 and POD 5, C-reactive protein (CRP) levels were significantly higher in patients with POPF than in those without (p=0.03 and p<0.001, respectively). Early drain removal regardless of DFA level may reduce the risk of developing POPF. CRP measured on POD 3 and POD 5 appeared to be a useful predictor of clinically relevant POPF.

Objective:The aim of this study was to assess safety and efficacy of pancreatic duct occlusion (PDO) with neoprene-based glue in selected patients undergoing pancreatoduodenectomy (PD) at high risk of postoperative pancreatic fistula (POPF).Background Data:PD is the reference standard approach for tumors of the pancreaticoduodenal region. POPF is the most relevant complication after PD. PDO has been proposed as an alternative to anastomosis to manage the pancreatic stump.Methods:A single-center, prospective, nonrandomized trial enrolled 100 consecutive PD for cancer. Patients at high risk for POPF according to Fistula Risk Score (FRS) >15% (≥6 points) were treated with PDO using neoprene glue (study cohort); patients with FRS ≤15% (≤5 points) received pancreaticojejunal anastomosis (PJA: control cohort). Primary endpoint was complication rate grade ≥3 according to Dindo–Clavien Classification (DCC). Other postoperative outcomes were monitored (ClinicalTrials.gov NCT03738787).Results:Fifty-one patients underwent PDO and 49 PJA. DCC ≥3, postoperative mortality, and POPF grade B-C were 25.5% versus 24.5% (P = 0.91), 5.9% versus 2% (P = 0.62), and 11.8% versus 16.3% (P = 0.51) in the study versus control cohort, respectively. At 1 and 3 years, new-onset diabetes was diagnosed in 13.7% and 36.7% of the study cohort versu 4.2% and 12.2% in controls (P = 0.007).Conclusions:PDO with neoprene-based glue is a safe technique that equalizes early outcome of selected patients at high risk of POPF to those at low risk undergoing PJA. Neoprene-based PDO, however, triples the risk of diabetes at 1 and 3 years.

Preoperative chemoradiotherapy diminishes the risk of postoperative pancreatic fistula after pancreatoduodenectomy

Use of radiation therapy in neoadjuvany treatment for pancreatic adenocarcinoma decreases risk of postoperative pancreatic fistula: A nsqip analysis