Robot-assisted pancreatoduodenectomy (RPD) is increasingly performed for cancer in the pancreatic head. Randomised evidence confirming its oncological safety and efficacy is lacking. The DIPLOMA-2x2 trial aims to compare the oncological safety of RPD versus OPD in terms of radicality (microscopically radical resection [R0] resection). We hypothesise that RPD is non-inferior to OPD in terms of radicality and superior regarding time to functional recovery. The DIPLOMA-2x2 trial is an investigator-initiated, international, multicentre, patient- and assessor-blinded randomised non-inferiority trial. The trial was conducted as a roll-over of the DIPLOMA-2 trial and includes 20 high-volume tertiary referral hospitals in 7 countries. Minimum surgeon’s experience is 60 RPD and 60 OPD, with a minimum annual centre volume of 30 RPD prior to trial initiation. Eligible patients are adults (≥18 years) with suspected or proven upfront resectable pancreatic ductal adenocarcinoma (PDAC) and distal cholangiocarcinoma (DCC) without any vascular involvement. Participants are randomised in a 2:1 ratio to RPD or OPD, respectively, stratified by tumour indication (proven PDAC versus other) and preoperative pancreatic fistula risk (high versus low). In total, 413 patients will be included, of which 137 previously randomised in DIPLOMA-2 and 276 newly recruited in DIPLOMA-2x2. Patients are blinded up to postoperative day 5. Primary outcome is pathological R0-resection rate (pR0; >1 mm tumour clearance at surgical resection margins and anatomical surfaces, 0 mm clearance at anterior surface), tested for non-inferiority with a −7

Background Preoperative endoscopic biliary drainage may lead to complications (16%-24%), potentially hampering surgical exploration. Endoscopic ultrasound-guided choledochoduodenostomy (EUS-CDS) may reduce drainage-related complications, however it is unknown whether EUS-CDS could in itself hamper surgical exploration as series with surgeon reported outcomes are lacking. Aim is to assess the impact of preoperative EUS-CDS on pancreatoduodenectomy. Method Consecutive patients who underwent pancreatoduodenectomy after preoperative biliary drainage were included in all eight centers that performed EUS-CDS in the mandatory Dutch Pancreatic Cancer Audit (Jan 2020-Dec 2022). Primary outcome was major postoperative complications. Secondary outcomes included bile leak grade B/C, postoperative pancreatic fistula (POPF) grade B/C, and overall postoperative complications. A propensity score matching (1:3) analysis was performed. Surgeons who performed a pancreatoduodenectomy after EUS-CDS were asked to complete a survey. Results Overall, 937 patients with pancreatoduodenectomy after preoperative biliary drainage were included (42 EUS-CDS, 895 ERCP). Major postoperative complications occurred in eight patients (19%) in the EUS-CDS group and 292 patients (33%) in the ERCP group (RR 0.50; 95%CI, 0.23-1.07). No significant differences were observed in overall complications (RR 0.95; 95%CI, 0.51-1.76), bile leak (RR 1.25; 95%CI, 0.31-4.98) or POPF (RR 0.62; 95%CI, 0.25-1.56). Results were similar after matching. The survey was completed for 29 pancreatoduodenectomies; surgery was not (n=13, 45%), ‘slightly’ (n=8, 28%), ‘clearly’ (n=5, 17%) or ‘severely’ (n=2, 7%) more complex because of the EUS-CDS. Conclusion This early experience suggests that preoperative biliary drainage with EUS-CDS does not increase the rate of complications after pancreatoduodenectomy and only infrequently hampers surgical exploration.

OBJECTIVE:To compare the incidence of major surgical complications between patients with (borderline) resectable pancreatic cancer treated with neoadjuvant FOLFIRINOX versus neoadjuvant gemcitabine-based chemoradiotherapy. SUMMARY OF BACKGROUND DATA:There are ongoing concerns regarding the possible adverse impact of neoadjuvant treatment on postoperative complication rates following pancreatectomy. METHODS:This study was a predefined analysis within the investigator-initiated nationwide randomized controlled PREOPANC-2 trial. Patients with (borderline) resectable pancreatic cancer were randomized to receive neoadjuvant FOLFIRINOX (FFX group) or neoadjuvant gemcitabine-based chemoradiotherapy (CRT group), both followed by surgery, and adjuvant gemcitabine only in the CRT group. Surgical complications including postoperative pancreatic fistula, postpancreatectomy hemorrhage, bile leakage, postoperative interventions, and 90-day mortality were compared, with major complications defined as Clavien-Dindo grade ≥3. RESULTS:Between June 5, 2018, and January 28, 2021, in total 375 patients were randomized, of whom 280 (74.7%) underwent pancreatic resection. A pancreatoduodenectomy was performed in 238 patients (85.0%), left pancreatectomy in 41 patients (14.6%), and total pancreatectomy in one patient (0.4%). The incidence of major surgical complications was similar between the FFX and CRT groups (26.8% versus 27.5%, P=0.884). No differences were observed in the risk of postoperative pancreatic fistula grade B/C (9.9% versus 4.4%, P=0.076), postpancreatectomy hemorrhage grade B/C (7.7% versus 3.6%, P=0.137), bile leakage grade B/C (2.5% versus 2.5%, P>0.999), and postoperative interventions (26.1% versus 26.8%, P=0.886). Surgical reoperation was performed in nine patients (6.3%) in the FFX group and eight patients (5.8%) in the CRT group (P=0.850). The postoperative 90-day mortality was 1.4% in the FFX group (2/142 patients) and 2.9% in the CRT group (4/138 patients) (P=0.442). CONCLUSIONS:In the PREOPANC-2 randomized trial, the risk of major surgical complications after pancreatic resection following neoadjuvant FOLFIRINOX or neoadjuvant gemcitabine-based chemoradiotherapy was similar with an overall low 90-day mortality.

Abstract Background The introduction of (m)FOLFIRINOX and gemcitabine-nab-paclitaxel has changed the perspective for patients with locally advanced pancreatic cancer (LAPC). Consequently, in experienced centres 23% of patients with LAPC undergo a resection with 5-year overall survival (OS) rates of up to 25%. In the Netherlands, the nationwide resection rate for LAPC remains low at 8%. The PREOPANC-4 program aims for a nationwide implementation of the international multidisciplinary best-practice to improve patient outcome. Methods Nationwide program implementing the international multidisciplinary best-practice for LAPC. In the training phase, multidisciplinary and surgical webinars are given by 4 international experts, leading to a clinical protocol, followed by surgical off-site and on-site proctoring sessions. In the implementation phase, the clinical protocol will be implemented in all centres, including a nationwide expert panel (2022–2024). Healthcare professionals will be trained in shared decision-making. Consecutive patients diagnosed with pathology-proven LAPC (i.e., arterial involvement > 90° and/or portomesenteric venous > 270° involvement or occlusion [DPCG criteria]) are eligible. Primary outcomes are median and 5-year OS from diagnosis, resection rate, in-hospital/30-day mortality and major morbidity (i.e., Clavien-Dindo grade ≥ IIIa), and radical resection (R0) rate. Secondary outcomes include quality of life, functioning, side effects, and patients’ healthcare satisfaction in all included patients. Outcomes will be compared with patients with borderline resectable pancreatic cancer (BRPC) treated with neoadjuvant FOLFIRINOX in the PREOPANC-2 trial (EudraCT: 2017–002036-17) and a historical cohort of patients with LAPC from the PACAP registry (NCT03513705). The existing prospective LAPC Registry and PACAP PROMs (NCT03513705) will be used for data collection. In qualitative interviews, treatment preferences, values, and experiences of LAPC patients, their relatives, and healthcare professionals will be assessed for the development of shared decision-making supportive tools. It is hypothesized that the program will double the nationwide LAPC resection rate to 16% with major morbidity < 50% and mortality ≤ 5%, and OS following resection similar to that observed in patients with BRPC. Discussion The PREOPANC-4 program aims to safely implement the international multidisciplinary best-practice for LAPC leading to benchmark outcomes for both short-term morbidity, mortality, and OS. Trial registration PREOPANC-4 program was registered at ClinicalTrials.gov (NCT05524090) on September 1, 2022.

OBJECTIVE:To assess nationwide surgical outcome after pancreatoduodenectomy (PD) in patients at very high risk for postoperative pancreatic fistula (POPF), categorized as ISGPS-D. SUMMARY BACKGROUND DATA: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. METHODS: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. RESULTS: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%). CONCLUSION: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.

The aim of this study is to identify learning curves for robotic gastro-enterostomy (RGE) during RPD and the predictive value of the objective structured assessment of technical skills (OSATS) score for DGE according to the Birkmeyer et al and UPMC method. In some series, robotic pancreatoduodenectomy (RPD) has been associated with increased risk of delayed gastric emptying (DGE). It is unclear whether this is attributable to learning curve. Improved surgical performance and experience has not yet been linked to a decrease in delayed gastric emptying in RPD. Post-hoc study of the prospective multicenter (LAELAPS-3) training program including videos of RGE during RPD. Surgical performance was scored with OSATS by two blinded graders. The main outcomes are the combined OSATS scores of two blinded graders over time (learning curve). Secondary outcome is the correlation between OSATS scores and clinically relevant DGE (grade B/C). Videos from 192 RGE anastomoses were included. DGE occurred in 42/192 (21.9%) patients. Mean OSATS score was 22.4 (SD±5.1) and predicted DGE (AUC 0.668, P<0.001). The predictive OSATS elements for DGE were gentleness (AUC 0.719, P<0.001), instrument handling (AUC 0.595 P=0.043), tissue exposure (AUC 0.625, P=0.009), and summary score (AUC 0.665, P<0.001). An OSATS score >25 was associated with a 59.9% reduced relative risk of grade B/C DGE (11.3% (8/71) vs 28.1% (34/121); OR 0.325, P=0.006). CUSUM analysis of RGE-OSATS identified a turning point at 34 procedures (27.5% (36/140) before vs 11.5% (6/52) after; OR 0.156, P=0.035. On multivariable analysis for grade B/C DGE, OSATS ≤25 remained an independent risk factor (OR 2.907, P=0.028). Better surgical performance during gastro-enteric anastomosis in RPD, as assessed by OSATS, is associated with a reduced rate of grade B/C DGE. OSATS could serve as a tool for competency-based training programs and quality-controlled implementation of RPD.

Background: Composite outcome measures aim to provide a more holistic view when determining the effectiveness and safety of surgical interventions. Recently, ‘Ideal Outcome’ (IO) harmonized the European and American composite outcome of pancreatic surgery. The rate of IO after pancreatoduodenectomy was 54% but is unknown after left pancreatectomy(LP). Methods: This transatlantic analysis included patients after LP from the audits in North America (NSQIP), Germany (StuDoQ), the Netherlands (DPCA), and Sweden (SNPPCR) (2014 – 2020). IO is obtained in the absence of (1)in-hospital mortality, (2)severe complications (Clavien-Dindo≥3), (3)postoperative pancreatic fistula (ISGPS grade B/C), (4)reoperation, (5)hospital stay exceeding the 75 th -percentile, and (6)readmission. Clinical predictors of IO were identified using a multivariable logistic regression. Results: Overall, 20,126 patients after LP were included (37.8% minimally invasive). The rate of IO after LP was 59.1%. The rate of IO varied among the four audits: North America 58.5%, Germany 53.4%, the Netherlands 56.9%, and Sweden 61.7% ( P <0.001). Among all variables, the rate of postoperative pancreatic fistula differed the most: North America 9.8%, Germany 23.9%, the Netherlands 20.5%, and Sweden 10.6% ( P <0.001). Minimally invasive LP was associated with higher rates of IO (65.4% vs 53.3%, P <0.001) compared to open LP. No difference in the IO was observed between robot-assisted and laparoscopic LP. Conclusion: The new composite outcome measure IO was reached in 59% patients after LP and varied between four transatlantic audits. Minimally invasive LP was associated with higher rates of IO. IO can be used for evaluating, comparing, and improving patient outcomes between the four audits, especially regarding postoperative pancreatic fistula.

Background Delayed gastric emptying is a major contributor to prolonged hospital stay following pancreatoduodenectomy. Although enhanced recovery after surgery guidelines recommend unrestricted feeding after pancreatoduodenectomy, nationwide studies evaluating the impact of different feeding strategies after surgery on delayed gastric emptying and length of hospital stay are limited. This study aimed to identify the use and impact of different feeding strategies after pancreatoduodenectomy on delayed gastric emptying and length of hospital stay. Methods This nationwide cohort study included consecutive patients after pancreatoduodenectomy from the Dutch Pancreatic Cancer Audit (2021-2023). Primary endpoints were delayed gastric emptying grade B/C and length of hospital stay. Feeding strategies were categorized based on structured interviews with representatives from 15 centres. Multilevel analysis was used to assess associations between feeding strategy, delayed gastric emptying, and length of hospital stay. Predictors of delayed gastric emptying were determined. Results Overall, 2354 patients undergoing pancreatoduodenectomy were included, of whom 526 (23%) developed delayed gastric emptying grade B/C. Median length of hospital stay was 13 days longer in patients with delayed gastric emptying (23 versus 10 days; P < 0.001). Feeding strategies were: unrestricted feeding (3 centres, 637 patients; delayed gastric emptying 18%); step-up feeding (9 centres, 1462 patients; delayed gastric emptying 24%); and artificial feeding (3 centres, 255 patients; delayed gastric emptying 25%). No association was observed between feeding strategy and delayed gastric emptying: step-up versus unrestricted feeding (odds ratio 1.14, 95% confidence interval 0.53 to 2.47) and artificial versus unrestricted feeding (odds ratio 1.76, 0.65 to 4.73). Similarly, no association was found between feeding strategy and length of hospital stay. The strongest predictor of delayed gastric emptying was pancreatic fistula after surgery (odds ratio 3.16, 2.47 to 4.05). Conclusion This study found no significant association between feeding strategy and incidence of delayed gastric emptying or length of hospital stay after pancreatoduodenectomy. Efforts to reduce delayed gastric emptying should focus on reducing pancreatic fistula after surgery.

Background: Preoperative planning of patients diagnosed with pancreatic head cancer is difficult and requires specific expertise. This pilot study assesses the added value of three-dimensional (3D) patient models and computer-aided detection (CAD) algorithms in determining the resectability of pancreatic head tumors. Methods: This study included 14 hepatopancreatobiliary experts from eight hospitals. The participants assessed three radiologically resectable and three radiologically borderline resectable cases in a simulated setting via crossover design. Groups were divided in controls (using a CT scan), a 3D group (using a CT scan and 3D models), and a CAD group (using a CT scan, 3D and CAD). For the perceived fulfillment of preoperative needs, the quality and confidence of clinical decision-making were evaluated. Results: A higher perceived ability to determine degrees and the length of tumor–vessel contact was reported in the CAD group compared to controls (p = 0.022 and p = 0.003, respectively). Lower degrees of tumor–vessel contact were predicted for radiologically borderline resectable tumors in the CAD group compared to controls (p = 0.037). Higher confidence levels were observed in predicting the need for vascular resection in the 3D group compared to controls (p = 0.033) for all cases combined. Conclusions: “CAD (including 3D) improved experts’ perceived ability to accurately assess vessel involvement and supports the development of evolving techniques that may enhance the diagnosis and treatment of pancreatic cancer”.

BACKGROUND:Robot-assisted pancreatoduodenectomy (RPD) aims to enhance postoperative recovery compared to open pancreatoduodenectomy (OPD). Although recent randomized trials confirmed the short-term safety of RPD, they did not confirm superiority or assess oncological safety. This nationwide observational cohort study compares oncological outcome after RPD versus OPD in patients with resectable pancreatic ductal adenocarcinoma (PDAC) and distal cholangiocarcinoma (DCC) without vascular contact. METHODS:All consecutive patients undergoing RPD and OPD for upfront resectable PDAC and DCC without vascular contact on preoperative imaging in the Netherlands were included. Data were obtained from the Netherlands Cancer Registry (2016-2023). Primary outcomes were overall survival (OS) and R0-resection rate. RESULTS:Overall, 1675 patients after pancreatoduodenectomy for upfront resectable PDAC and DCC were included (375 RPD; 1300 OPD). Adjusted median OS was 23 months after RPD versus 22 months after OPD, with comparable 5-year survival rate (23.3% versus 22.4%, HR 0.96 [0.82-1.14], P = 0.665). The R0-resection rate was comparable (57.1% versus 59.7%, P = 0.368). RPD was associated with a shorter hospital stay (median 9 versus 11 days, P < 0.001) and comparable in-hospital/30-day (3.1% versus 2.6%, P = 0.618) and 90-day mortality rate (7.7% versus 6.2%, P = 0.276). In patients with PDAC, no differences in receipt (58.2% versus 58.7%, P = 0.900), time to start (median 54 versus 58 days, P = 0.107), or completion of adjuvant chemotherapy (30.4% versus 30.4%, P = 0.999) were observed. CONCLUSIONS:In this nationwide study, oncological outcome including 5-year survival was comparable between patients undergoing RPD and OPD for upfront resectable PDAC and DCC without vascular contact without differences in the use of adjuvant therapy for PDAC.

BACKGROUND:Pancreatic resections for pancreatic neuroendocrine tumors (pNET) may experience a higher complication rate than for pancreatic ductal adenocarcinoma (PDAC). This study aimed to determine the rate of the novel composite "Ideal Outcome" measure after resection for pNET, using PDAC as reference. METHODS:This observational cohort study included all consecutive patients after pancreatic resection for pNET and PDAC using the nationwide Dutch Pancreatic Cancer Audit (2014-2021). The primary outcome was Ideal Outcome; absence of postoperative mortality, postoperative pancreatic fistulas (POPF) grade B/C, other major complications, prolonged length of stay, reoperations and readmissions. RESULTS:In total, 524 pNET and 2851 PDAC resections were included. The rate of Ideal Outcome was lower after resection for pNET (47.7% versus 55.7%; P<0.001) as compared to PDAC. This difference was driven by a lower rate of Ideal Outcome after pancreatoduodenectomy for pNET (37.7% versus 56.3%; P<0.001), with no difference after left pancreatectomy (54.5% versus 52.5%; P=0.598). Among the individual components of Ideal Outcome after pancreatoduodenectomy, the largest difference was a four times higher rate of POPF (32.1% versus 7.9%; P<0.001) after resection of pNET. CONCLUSION:Patients undergoing pancreatoduodenectomy for pNET have a reduced Ideal Outcome rate compared to patients with PDAC, related to a fourfold increased risk of POPF. This highlights the value of pNET-specific patient counseling and the need for effective POPF mitigation strategies.

OBJECTIVE:The aim of this study is to identify learning curves for robotic gastro-enterostomy (RGE) during RPD and the predictive value of the objective structured assessment of technical skills (OSATS) score for DGE according to the Birkmeyer et al and UPMC method. SUMMARY OF BACKGROUND DATA:In some series, robotic pancreatoduodenectomy (RPD) has been associated with increased risk of delayed gastric emptying (DGE). It is unclear whether this is attributable to learning curve. Improved surgical performance and experience has not yet been linked to a decrease in delayed gastric emptying in RPD. METHODS:Post-hoc study of the prospective multicenter (LAELAPS-3) training program including videos of RGE during RPD. Surgical performance was scored with OSATS by two blinded graders. The main outcomes are the combined OSATS scores of two blinded graders over time (learning curve). Secondary outcome is the correlation between OSATS scores and clinically relevant DGE (grade B/C). RESULTS:Videos from 192 RGE anastomoses were included. DGE occurred in 42/192 (21.9%) patients. Mean OSATS score was 22.4 (SD±5.1) and predicted DGE (AUC 0.668, P<0.001). The predictive OSATS elements for DGE were gentleness (AUC 0.719, P<0.001), instrument handling (AUC 0.595 P=0.043), tissue exposure (AUC 0.625, P=0.009), and summary score (AUC 0.665, P<0.001). An OSATS score >25 was associated with a 59.9% reduced relative risk of grade B/C DGE (11.3% (8/71) vs 28.1% (34/121); OR 0.325, P=0.006). CUSUM analysis of RGE-OSATS identified a turning point at 34 procedures (27.5% (36/140) before vs 11.5% (6/52) after; OR 0.156, P=0.035. On multivariable analysis for grade B/C DGE, OSATS ≤25 remained an independent risk factor (OR 2.907, P=0.028). CONCLUSIONS:Better surgical performance during gastro-enteric anastomosis in RPD, as assessed by OSATS, is associated with a reduced rate of grade B/C DGE. OSATS could serve as a tool for competency-based training programs and quality-controlled implementation of RPD.

Objective: To determine if video grading using Objective Structured Assessment of Technical Skills (OSATS) could estimate the risk of postoperative bile leak (BL) after robotic pancreatoduodenectomy (RPD) and to identify a learning curve effect. Summary Background Data: The hepaticojejunostomy (HJ) bile leak rate after RPD is rather high with 10% and may be improved by structured training and skills. Robotic HJ therefore requires confirmation of adequate performance. Grading of surgical performance during HJ could be used in competency-based surgical training. Methods: Post-hoc analysis of patients included the Dutch LAELAPS-3 RPD training program in 6 centers. Technical performance during robotic HJ was graded by two blinded graders using OSATS (attainable scores 6-30). Primary outcome was grade B/C bile leak according to the ISGLS. Logistic regression determined the performance cut-off and CUSUM analysis identified the learning curve. Results: Videos from robotic HJ in 259 patients were included with a 6.9% rate of grade B/C bile leak (n=18/259). The median OSATS for the HJ was 25.0 [22–27], with an OSATS score>21 associated with a reduced risk of BL. The rate of BL was 5.1% in patients for OSATS>21 and 12.5% for OSATS ≤21, amounting to a relative reduction of 59.2% and an absolute reduction of 7.4% (8/64 vs. 10/195, OR 0.378, P =0.013). These findings remained similar when only including grade C BL: OR 0.076, P =0.004. On multivariable analysis for grade B/C BL, the only significant predictive factor was OSATS>21: OR 0.273, P =0.025. Stabilization of the CUSUM learning curve for grade B/C BL was reached at 19 RPD procedures, and after 44 procedures the learning curve showed a continuous downward trend. The rate of grade B/C BL was significantly lower beyond 19 RPD: 5.6% versus 8.6% (8/143 vs. 10/116, OR 0.710, P =0.040). Conclusions: The risk of postoperative BL after RPD is strongly associated with surgical performance during robotic HJ as objectified using OSATS. This approach can be used for rapid assessment of the learning curve and competency-based surgical training, aiming for a safe implementation RPD.

Given the poor survival and relatively poor performance of hepato-pancreato-biliary (HPB) cancers on data quality indicators for cancer registries, we assessed trends in incidence, survival, and data quality of HPB cancers within the Netherlands Cancer Registry (NCR). All primary solid liver, gallbladder, biliary tract, and pancreatic cancers (topography C22-23-24-25) diagnosed between 1989 and 2022 were included (n = 109,552). Cancer mortality data were obtained from Statistics Netherlands. For incidence and mortality, revised European Age-Standardised Rates, and for survival, age-standardised 5-year relative survival (AS-5yRS) were calculated. Over time, incidence rates increased for liver (males: 3.0 to 8.2/100,000; females 1.2 to 3.9/100,000), pancreatic (males: 15.8 to 18.5/100,000; females: 11.1 to 15.3/100,000), and biliary tract cancers in males (3.9 to 4.9/100,000; not females: 3.3 to 2.9/100,000). Gallbladder cancer incidence decreased until 2005 (males: 1.5 to 0.8/100,000, females 4.0 to 1.5/100,000). Mortality trends mirrored incidence patterns, with smaller increases. AS-5yRS improved across all HPB cancers with the largest increase in liver (males: 3.4% to 20.8%; females: 6.7% to 18.3%) and pancreatic cancers (males: 2.3% to 10.4%; females: 3.5% to 11.3%). Since 2010, survival gains for gallbladder (males: 8.4% to 16.3%; females: 12.2% to 15.8%) and biliary tract cancers (males: 11.7% to 19.1%; females: 10.7% to 15.6%) have stagnated. Mortality-to-Incidence ratios versus 5-year relative survival for liver and pancreatic cancers improved toward equilibrium. Data quality improved (e.g., autopsy, unspecified morphology) or remained stable (multiple primaries). Both incidence and survival rates of primary HPB cancers have increased over time. Increased completeness of incidence data was attributed to changed notification sources.

To evaluate the utilization of routine imaging and the impact on survival after resection of pancreatic ductal adenocarcinoma (PDAC). Evidence on the benefit of routine imaging after resection of PDAC on early detection and treatment of disease recurrence is currently lacking. The availability of more effective treatment options for PDAC recurrence may have increased the utilization of routine imaging in daily clinical practice. Patients who underwent resection of PDAC in the Netherlands (2014-2019) were included in this nationwide observational cohort study (NCT04605237). Patients were stratified based on surveillance strategy. Median overall survival (OS) was assessed using Kaplan-Meier survival curves. The association between surveillance strategy and asymptomatic recurrence, recurrence treatment, and OS was assessed using multivariable logistic regression and Cox proportional hazard analysis, respectively. A total of 1311 patients were included, with a median follow-up of 45 (IQR 34-61) months. Routine imaging was used in 139 patients (11%), with a median OS of 43 (IQR 35-not reached) months, compared to 22 (IQR 21-24) months in 1172 patients (89%) with a symptomatic surveillance (P<0.001). Routine imaging was associated with asymptomatic recurrence (OR 3.79 [95% CI 2.27-6.32]; P<0.001), recurrence treatment (OR 2.50 [95% CI 1.21-5.18]; P=0.01) and improved OS (HR 0.56 [95% CI 0.44-0.71]; P<0.001). Routine imaging after resection of PDAC was independently associated with the detection of asymptomatic disease recurrence, recurrence treatment and improved survival, which further advocates towards inclusion of routine imaging after PDAC resection in clinical guidelines.

BACKGROUND:Preoperative endoscopic biliary drainage may lead to complications (16 %-24 %), potentially hampering surgical exploration. Endoscopic ultrasound-guided choledochoduodenostomy (EUS-CDS) may reduce drainage-related complications; however, in the absence of surgeon-reported outcomes, it is unknown whether EUS-CDS may hamper surgical exploration. This study assessed the impact of preoperative EUS-CDS on pancreatoduodenectomy. METHOD:Consecutive patients who underwent pancreatoduodenectomy after preoperative biliary drainage were included in all eight centers performing EUS-CDS in the mandatory Dutch Pancreatic Cancer Audit (Jan 2020-Dec 2022). The primary outcome was major postoperative complications. Secondary outcomes included bile leak grade B/C, postoperative pancreatic fistula (POPF) grade B/C, and overall postoperative complications. A propensity score-matching (1:3) analysis was performed. Surgeons performing pancreatoduodenectomy after EUS-CDS completed a survey on surgical difficulty. RESULTS:937 patients with pancreatoduodenectomy after preoperative biliary drainage were included (42 EUS-CDS, 895 endoscopic retrograde cholangiopancreatography [ERCP]). Major postoperative complications occurred in 8 patients (19.0 %) in the EUS-CDS group and 292 (32.6 %) in the ERCP group (relative risk [RR] 0.50; 95 %CI 0.23-1.07). No significant differences were observed in overall complications (RR 0.95; 95 %CI 0.51-1.76), bile leak (RR 1.25; 95 %CI 0.31-4.98), or POPF (RR 0.62; 95 %CI 0.25-1.56). Results were similar after matching. The survey was completed for 29 pancreatoduodenectomies; surgery was not (13, 45 %), "slightly" (9, 31 %), "clearly" (5,17 %), and "severely" (2, 7 %) more complex because of EUS-CDS. CONCLUSION:This early experience suggests that preoperative biliary drainage with EUS-CDS does not increase the rate of complications after pancreatoduodenectomy and only infrequently hampers surgical exploration.

BACKGROUND AND AIMS:Frailty and sarcopenia are associated with morbidity and mortality in older patients with cancer. The aim of this study was to examine the association of frailty with skeletal muscle index (SMI) and muscle attenuation (MA) on preoperative CT-scans in older patients with pancreatic cancer. METHODS:A single-center retrospective study was performed in patients aged ≥70 years with pancreatic cancer. Frailty was assessed by an abbreviated GA screening. Preoperative SMI and MA were determined by computed tomography (CT) scan analysis. The association of frailty and individual frailty domains with SMI and MA was assessed using linear regression analyses. RESULTS:101 patients were included of which 15 (14.9 %) were frail. Frailty was associated with lower SMI (adjusted β: -5.07 cm2/m2; 95 % CI: -8.77-1.36) and MA (adjusted β: -5.70 HU; 95 % CI: -9.63-1.77). Both impaired functionality and risk of delirium were associated with lower SMI (adjusted β: -7.01 cm2/m2; 95 % CI: -11.69-2.33 and adjusted β: -4.58 cm2/m2; 95 % CI: -8.22-0.95, respectively). Impaired functionality was also associated with lower MA (adjusted β: -6.88 HU; 95 % CI: -11.89-1.87). CONCLUSION:Frailty and impaired functionality were associated with lower SMI and MA. Risk of delirium was independently associated with lower SMI in preoperative older patients with pancreatic cancer. These results suggests that SMI and MA should be included in standard GA screening to better identify high-risk patients and enable more targeted treatment selection.

Background: This study evaluates leading causes of in-hospital mortality after pancreatic resection nationwide to determine areas for improvement. Methods: This observational cohort study included all in-hospital mortality after pancreatic resection in the Netherlands (2014-2019). Each fatality was considered to be caused by local complications (i.e. directly related to surgery, located in surgical area) or systemic complications (e.g. cardiac or pulmonary). A blinded Expert Committee reviewed the postoperative course leading to death and identified potential quality improvement measures. Results: Out of 5345 patients undergoing pancreatic resection, 149 patients (2.8 %) died in-hospital. Local complications caused death in 126 patients (85 %) and systemic complications in 23 patients (15 %). Concerning local complications, the common leading causes of death were postoperative pancreatic fistula (n = 41) and thrombosis of vascular reconstructions (n = 23). Systemic cardiac (n = 8) and pulmonary (n = 7) complications caused death frequently. Potential areas for improvement were failure to rescue (n = 89; 60 %), prevention of complications (n = 34, 23 %) and patient selection (n = 14; 9 %). Conclusion: Local complications often caused death after pancreatic resection, mainly pancreatic fistula and vascular reconstruction failure. Failure to rescue was considered the most important area for improvement to decrease in-hospital mortality further.

BACKGROUND:The PREOPANC-2 trial aimed to evaluate whether neoadjuvant FOLFIRINOX improved overall survival compared with neoadjuvant gemcitabine-based chemoradiotherapy followed by adjuvant gemcitabine in patients with resectable or borderline resectable pancreatic ductal adenocarcinoma (PDAC). METHODS:In this investigator-initiated, open-label, nationwide, phase 3 randomised trial, patients aged 18 years or older with resectable or borderline resectable PDAC and a WHO performance status of 0 or 1 were enrolled across 19 Dutch centres. Patients in the FOLFIRINOX (FFX) group received FOLFIRINOX (85 mg/m2 intravenous oxaliplatin, 180 mg/m2 intravenous irinotecan, 400 mg/m2 intravenous leucovorin, followed by a 400 mg/m2 intravenous fluorouracil bolus and then continuous infusion at 2400 mg/m2 intravenously over 46 h every 14 days for eight cycles) followed by surgery without adjuvant treatment. Patients in the chemoradiotherapy (CRT) group received three cycles of neoadjuvant gemcitabine (1000 mg/m2 intravenously on days 1, 8, and 15 of each 28-day cycle and on days 1 and 8 only for cycles one and three) combined with hypofractionated radiotherapy (36 Gy in 15 fractions) during the second cycle only, followed by surgery and four cycles of adjuvant gemcitabine. Randomisation (1:1) was done using a minimisation technique and stratified by resectability status (resectable vs borderline resectable disease) and centre. The primary endpoint was overall survival in the modified intention-to-treat population, after excluding ineligible patients. Data on race and ethnicity were not collected. This trial is registered with EudraCT (2017-002036-17) and is complete. FINDINGS:From June 5, 2018, to Jan 28, 2021, 375 patients were randomly assigned to the FFX group (n=188) or the CRT group (n=187). Six patients (three per group) were excluded due to ineligibility (n=4) or immediate withdrawal of informed consent after randomisation (n=2). 208 (56%) of 369 patients were male and 161 (44%) were female. After a median follow-up of 42·3 months (IQR 35·7-48·7), median overall survival was 21·9 months (95% CI 17·7-27·0) in the FFX group versus 21·3 months (16·8-25·5) in the CRT group (HR 0·88 [95% CI 0·69-1·13], p=0·32). The most common grade 3-4 adverse events were neutropenia (43 [25%] of 175 in the FFX group vs 38 [22%] of 176 in the CRT group), diarrhoea (41 [23%] vs two [1%]), and leukopenia (14 [8%] vs 26 [15%]). Serious adverse events occurred in 85 (49%) patients in the FFX group compared with 75 (43%) in the CRT group (p=0·26). Adverse events of grades 3 or worse occurred in 117 (67%) patients in the FFX group versus 106 (60%) patients in the CRT group (p=0·20). Treatment-related deaths occurred in two (1%) patients in the FFX group (multi-organ failure and intestinal mucositis) and one (1%) patient in the CRT group (upper gastrointestinal haemorrhage). INTERPRETATION:This randomised trial did not show a difference in overall survival between neoadjuvant FOLFIRINOX and neoadjuvant gemcitabine-based chemoradiotherapy in patients with resectable or borderline resectable PDAC. Both neoadjuvant treatment regimens may be considered in these patients. FUNDING:Dutch Cancer Society and ZonMw.