Dutch Pancreatic Cancer Audit Research Articles

The Difficulty of Detecting Occult Metastases in Patients with Potentially Resectable Pancreatic Cancer: Development and External Validation of a Preoperative Prediction Model.

Occult metastases are detected in 10-15% of patients during exploratory laparotomy for pancreatic cancer. This study developed and externally validated a model to predict occult metastases in patients with potentially resectable pancreatic cancer. Model development was performed within the Dutch Pancreatic Cancer Audit, including all patients operated for pancreatic cancer (January 2013-December 2017). Multivariable logistic regression analysis based on the Akaike Information Criteria was performed with intraoperative pathologically proven metastases as the outcome. The model was externally validated with a cohort from the University Hospital of Verona (January 2013-December 2017). For model development, 2262 patients were included of whom 235 (10%) had occult metastases, located in the liver (n = 143, 61%), peritoneum (n = 73, 31%), or both (n = 19, 8%). The model included age (OR 1.02, 95% CI 1.00-1.03), BMI (OR 0.96, 95% CI 0.93-0.99), preoperative nutritional support (OR 1.73, 95% CI 1.01-2.74), tumor diameter (OR 1.60, 95% CI 1.04-2.45), tumor composition (solid vs. cystic) (OR 2.33, 95% CI 1.20-4.35), and indeterminate lesions on preoperative imaging (OR 4.01, 95% CI 2.16-7.43). External validation showed poor discrimination with a C-statistic of 0.56. Although some predictor variables were significantly associated with occult metastases, the model performed insufficiently at external validation.

Preoperative chemoradiotherapy but not chemotherapy is associated with reduced risk of postoperative pancreatic fistula after pancreatoduodenectomy for pancreatic ductal adenocarcinoma: a nationwide analysis

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.

Early experience with robotic pancreatoduodenectomy versus open pancreatoduodenectomy: nationwide propensity-score-matched analysis.

Although robotic pancreatoduodenectomy has shown promising outcomes in experienced high-volume centres, it is unclear whether implementation on a nationwide scale is safe and beneficial. The aim of this study was to compare the outcomes of the early experience with robotic pancreatoduodenectomy versus open pancreatoduodenectomy in the Netherlands. This was a nationwide retrospective cohort study of all consecutive patients who underwent robotic pancreatoduodenectomy or open pancreatoduodenectomy who were registered in the mandatory Dutch Pancreatic Cancer Audit (18 centres, 2014-2021), starting from the first robotic pancreatoduodenectomy procedure per centre. The main endpoints were major complications (Clavien-Dindo grade greater than or equal to III) and in-hospital/30-day mortality. Propensity-score matching (1 : 1) was used to minimize selection bias. Overall, 701 patients who underwent robotic pancreatoduodenectomy and 4447 patients who underwent open pancreatoduodenectomy were included. Among the eight centres that performed robotic pancreatoduodenectomy, the median robotic pancreatoduodenectomy experience was 86 (range 48-149), with a 7.3% conversion rate. After matching (698 robotic pancreatoduodenectomy patients versus 698 open pancreatoduodenectomy control patients), no significant differences were found in major complications (40.3% versus 36.2% respectively; P = 0.186), in-hospital/30-day mortality (4.0% versus 3.1% respectively; P = 0.326), and postoperative pancreatic fistula grade B/C (24.9% versus 23.5% respectively; P = 0.578). Robotic pancreatoduodenectomy was associated with a longer operating time (359 min versus 301 min; P < 0.001), less intraoperative blood loss (200 ml versus 500 ml; P < 0.001), fewer wound infections (7.4% versus 12.2%; P = 0.008), and a shorter hospital stay (11 days versus 12 days; P < 0.001). Centres performing greater than or equal to 20 robotic pancreatoduodenectomies annually had a lower mortality rate (2.9% versus 7.3%; P = 0.009) and a lower conversion rate (6.3% versus 11.2%; P = 0.032). This study indicates that robotic pancreatoduodenectomy was safely implemented nationwide, without significant differences in major morbidity and mortality compared with matched open pancreatoduodenectomy patients. Randomized trials should be carried out to verify these findings and confirm the observed benefits of robotic pancreatoduodenectomy versus open pancreatoduodenectomy.

Nationwide Outcome after Pancreatoduodenectomy in Patients at very High Risk (ISGPS-D) for Postoperative Pancreatic Fistula.

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.

Machine learning versus logistic regression for the prediction of complications after pancreatoduodenectomy

BackgroundMachine learning is increasingly advocated to develop prediction models for postoperative complications. It is, however, unclear if machine learning is superior to logistic regression when using structured clinical data. Postoperative pancreatic fistula and delayed gastric emptying are the two most common complications with the biggest impact on patient condition and length of hospital stay after pancreatoduodenectomy. This study aimed to compare the performance of machine learning and logistic regression in predicting pancreatic fistula and delayed gastric emptying after pancreatoduodenectomy. MethodsThis retrospective observational study used nationwide data from 16 centers in the Dutch Pancreatic Cancer Audit between January 2014 and January 2021. The area under the curve of a machine learning and logistic regression model for clinically relevant postoperative pancreatic fistula and delayed gastric emptying were compared. ResultsOverall, 799 (16.3%) patients developed a postoperative pancreatic fistula, and 943 developed (19.2%) delayed gastric emptying. For postoperative pancreatic fistula, the area under the curve of the machine learning model was 0.74, and the area under the curve of the logistic regression model was 0.73. For delayed gastric emptying, the area under the curve of the machine learning model and logistic regression was 0.59. ConclusionMachine learning did not outperform logistic regression modeling in predicting postoperative complications after pancreatoduodenectomy.

Surgical Outcome After Pancreatoduodenectomy for Duodenal Adenocarcinoma Compared with Other Periampullary Cancers: A Nationwide Audit Study

BackgroundSurgical outcome after pancreatoduodenectomy for duodenal adenocarcinoma could differ from pancreatoduodenectomy for other cancers, but large multicenter series are lacking. This study aimed to determine surgical outcome in patients after pancreatoduodenectomy for duodenal adenocarcinoma, compared with other periampullary cancers, in a nationwide multicenter cohort.MethodsAfter pancreatoduodenectomy for cancer between 2014 and 2019, consecutive patients were included from the nationwide, mandatory Dutch Pancreatic Cancer Audit. Patients were stratified by diagnosis. Baseline, treatment characteristics, and postoperative outcome were compared between groups. The association between diagnosis and major complications (Clavien–Dindo grade III or higher) was assessed via multivariable regression analysis.ResultsOverall, 3113 patients, after pancreatoduodenectomy for cancer, were included in this study: 264 (8.5%) patients with duodenal adenocarcinomas and 2849 (91.5%) with other cancers. After pancreatoduodenectomy for duodenal adenocarcinoma, patients had higher rates of major complications (42.8% vs. 28.6%; p < 0.001), postoperative pancreatic fistula (International Study Group of Pancreatic Surgery [ISGPS] grade B/C; 23.1% vs. 13.4%; p < 0.001), complication-related intensive care admission (14.3% vs. 10.3%; p = 0.046), re-interventions (39.8% vs. 26.6%; p < 0.001), in-hospital mortality (5.7% vs. 3.1%; p = 0.025), and longer hospital stay (15 days vs. 11 days; p < 0.001) compared with pancreatoduodenectomy for other cancers. In multivariable analysis, duodenal adenocarcinoma was independently associated with major complications (odds ratio 1.14, 95% confidence interval 1.03–1.27; p = 0.011).ConclusionPancreatoduodenectomy for duodenal adenocarcinoma is associated with higher rates of major complications, pancreatic fistula, re-interventions, and in-hospital mortality compared with patients undergoing pancreatoduodenectomy for other cancers. These findings should be considered in patient counseling and postoperative management.

Outcome of Pancreatic Surgery During the First 6 Years of a Mandatory Audit Within the Dutch Pancreatic Cancer Group.

To describe outcome after pancreatic surgery in the first 6 years of a mandatory nationwide audit. Within the Dutch Pancreatic Cancer Group, efforts have been made to improve outcome after pancreatic surgery. These include collaborative projects, clinical auditing, and implementation of an algorithm for early recognition and management of postoperative complications. However, nationwide changes in outcome over time have not yet been described. This nationwide cohort study included consecutive patients after pancreatoduodenectomy (PD) and distal pancreatectomy from the mandatory Dutch Pancreatic Cancer Audit (January 2014-December 2019). Patient, tumor, and treatment characteristics were compared between 3 time periods (2014-2015, 2016-2017, and 2018-2019). Short-term surgical outcome was investigated using multilevel multivariable logistic regression analyses. Primary endpoints were failure to rescue (FTR) and in-hospital mortality. Overall, 5345 patients were included, of whom 4227 after PD and 1118 after distal pancreatectomy. After PD, FTR improved from 13% to 7.4% [odds ratio (OR) 0.64, 95% confidence interval (CI) 0.50-0.80, P <0.001] and in-hospital mortality decreased from 4.1% to 2.4% (OR 0.68, 95% CI 0.54-0.86, P =0.001), despite operating on more patients with age >75 years (18%-22%, P =0.006), American Society of Anesthesiologists score ≥3 (19%-31%, P <0.001) and Charlson comorbidity score ≥2 (24%-34%, P <0.001). The rates of textbook outcome (57%-55%, P =0.283) and major complications remained stable (31%-33%, P =0.207), whereas complication-related intensive care admission decreased (13%-9%, P =0.002). After distal pancreatectomy, improvements in FTR from 8.8% to 5.9% (OR 0.65, 95% CI 0.30-1.37, P =0.253) and in-hospital mortality from 1.6% to 1.3% (OR 0.88, 95% CI 0.45-1.72, P =0.711) were not statistically significant. During the first 6 years of a nationwide audit, in-hospital mortality and FTR after PD improved despite operating on more high-risk patients. Several collaborative efforts may have contributed to these improvements.

Fistula Risk Score for Auditing Pancreatoduodenectomy: The Auditing-FRS.

To develop a fistula risk score for auditing, to be able to compare postoperative pancreatic fistula (POPF) after pancreatoduodenectomy among hospitals. For proper comparisons of outcomes in surgical audits, case-mix variation should be accounted for. This study included consecutive patients after pancreatoduodenectomy from the mandatory nationwide Dutch Pancreatic Cancer Audit. Derivation of the score was performed with the data from 2014 to 2018 and validation with 2019 to 2020 data. The primary endpoint of the study was POPF (grade B or C). Multivariable logistic regression analysis was performed for case-mix adjustment of known risk factors. In the derivation cohort, 3271 patients were included, of whom 479 (14.6%) developed POPF. Male sex [odds ratio (OR)=1.34; 95% confidence interval (CI): 1.09-1.66], higher body mass index (OR=1.07; 95% CI: 1.05-1.10), a final diagnosis other than pancreatic ductal adenocarcinoma/pancreatitis (OR=2.41; 95% CI: 1.90-3.06), and a smaller duct diameter (OR=1.43/mm decrease; 95% CI: 1.32-1.55) were independently associated with POPF. Diabetes mellitus (OR=0.73; 95% CI: 0.55-0.98) was independently associated with a decreased risk of POPF. Model discrimination was good with a C -statistic of 0.73 in the derivation cohort and 0.75 in the validation cohort (n=913). Hospitals differed in particular in the proportion of pancreatic ductal adenocarcinoma/pancreatitis patients, ranging from 36.0% to 58.1%. The observed POPF risk per center ranged from 2.9% to 25.4%. The expected POPF rate based on the 5 risk factors ranged from 11.6% to 18.0% among hospitals. The auditing fistula risk score was successful in case-mix adjustment and enables fair comparisons of POPF rates among hospitals.

Short- and Long-Term Outcomes of Pancreatic Cancer Resection in Elderly Patients: A Nationwide Analysis

BackgroundThe number of elderly patients with pancreatic cancer is growing, however clinical data on the short-term outcomes, rate of adjuvant chemotherapy, and survival in these patients are limited and we therefore performed a nationwide analysis.MethodsData from the prospective Dutch Pancreatic Cancer Audit were analyzed, including all patients undergoing pancreatic cancer resection between January 2014 and December 2016. Patients were classified into two age groups: <75 and ≥75 years. Major complications (Clavien–Dindo grade 3 or higher), 90-day mortality, rates of adjuvant chemotherapy, and survival were compared between age groups. Factors associated with start of adjuvant chemotherapy and survival were evaluated with logistic regression and multivariable Cox regression analysis.ResultsOf 836 patients, 198 were aged ≥75 years (24%) and 638 were aged <75 years (76%). Median follow-up was 38 months (interquartile range [IQR] 31–47). Major complications (31% vs. 28%; p = 0.43) and 90-day mortality (8% vs. 5%; p = 0.18) did not differ. Adjuvant chemotherapy was started in 37% of patients aged ≥75 years versus 69% of patients aged <75 years (p < 0.001). Median overall survival (OS) was 15 months (95% confidence interval [CI] 14–18) versus 21 months (95% CI 19–24; p < 0.001). Age ≥75 years was not independently associated with OS (hazard ratio 0.96, 95% CI 0.79–1.17; p = 0.71), but was associated with a lower rate of adjuvant chemotherapy (odds ratio 0.27, 95% CI 0.18–0.40; p < 0.001).ConclusionsThe rate of major complications and 90-day mortality after pancreatic resection did not differ between elderly and younger patients; however, elderly patients were less often treated with adjuvant chemotherapy and their OS was shorter.

Nationwide Validation of the 8th American Joint Committee on Cancer TNM Staging System and Five Proposed Modifications for Resected Pancreatic Cancer

BackgroundThe prognostic value of four proposed modifications to the 8th American Joint Committee on Cancer (AJCC) TNM staging system has yet to be evaluated. This study aimed to validate five proposed modifications.MethodsPatients who underwent pancreatic ductal adenocarcinoma resection (2014–2016), as registered in the prospective Dutch Pancreatic Cancer Audit, were included. Stratification and prognostication of TNM staging systems were assessed using Kaplan–Meier curves, Cox proportional hazard analyses, and C-indices. A new modification was composed based on overall survival (OS).ResultsOverall, 750 patients with a median OS of 18 months (interquartile range 10–32) were included. The 8th edition had an increased discriminative ability compared with the 7th edition {C-index 0.59 (95% confidence interval [CI] 0.56–0.61) vs. 0.56 (95% CI 0.54–0.58)}. Although the 8th edition showed a stepwise decrease in OS with increasing stage, no differences could be demonstrated between all substages; stage IIA vs. IB (hazard ratio [HR] 1.30, 95% CI 0.80–2.09; p = 0.29) and stage IIB vs. IIA (HR 1.17, 95% CI 0.75–1.83; p = 0.48). The four modifications showed comparable prognostic accuracy (C-index 0.59–0.60); however, OS did not differ between all modified TNM stages (ns). The new modification, migrating T3N1 patients to stage III, showed a C-index of 0.59, but did detect significant survival differences between all TNM stages (p < 0.05).ConclusionsThe 8th TNM staging system still lacks prognostic value for some categories of patients, which was not clearly improved by four previously proposed modifications. The modification suggested in this study allows for better prognostication in patients with all stages of disease.

Somatostatin analogues for the prevention of pancreatic fistula after open pancreatoduodenectomy: A nationwide analysis

BackgroundSomatostatin analogues (SA) are currently used to prevent postoperative pancreatic fistula (POPF) development. However, its use is controversial. This study investigated the effect of different SA protocols on the incidence of POPF after pancreatoduodenectomy in a nationwide population. MethodsAll patients undergoing elective open pancreatoduodenectomy were included from the Dutch Pancreatic Cancer Audit (2014–2017). Patients were divided into six groups: no SA, octreotide, lanreotide, pasireotide, octreotide only in high-risk (HR) patients and lanreotide only in HR patients. Primary endpoint was POPF grade B/C. The updated alternative Fistula Risk Score was used to compare POPF rates across various risk scenarios. Results1992 patients were included. Overall POPF rate was 13.1%. Lanreotide (10.0%), octreotide-HR (9.4%) and no protocol (12.7%) POPF rates were lower compared to the other protocols (varying from 15.1 to 19.1%, p = 0.001) in crude analysis. Sub-analysis in patients with HR of POPF showed a significantly lower rate of POPF when treated with lanreotide (10.0%) compared to no protocol, octreotide and pasireotide protocol (21.6–26.9%, p = 0.006). Octreotide-HR and lanreotide-HR protocol POPF rates were comparable to lanreotide protocol, however not significantly different from the other protocols. Multivariable regression analysis demonstrated lanreotide protocol to be positively associated with a low odds-ratio (OR) for POPF (OR 0.387, 95% CI 0.180–0.834, p = 0.015). In-hospital mortality rates were not affected. ConclusionUse of lanreotide in all patients undergoing pancreatoduodenectomy has a potential protective effect on POPF development. Protocols for HR patients only might be favorable too. However, future studies are warranted to confirm these findings.

First Four Years of a Nationwide Audit: Did Clinical Practice and Outcomes in Pancreatic Surgery Improve?

Introducion: The Dutch Pancreatic Cancer Audit (DPCA) has been established to monitor and improve nationwide outcomes of pancreatic surgery. This study aimed to describe changes in clinical practice and outcomes of pancreatic surgery in the first four years of the DPCA. Methods: Consecutive patients who underwent pancreatoduodenectomy or distal pancreatectomy were registered in the mandatory nationwide DPCA. Results were analyzed in the time periods 2014-2015 and 2016-2017. Trends in patient, tumor, and treatment characteristics were assessed using univariable regression analyses. Short-term surgical outcomes were investigated using multilevel multivariable logistic regression analyses. Results: Out of 3508 patients, 2780 (79.2%) underwent pancreatoduodenectomy and 728 (20.8%) distal pancreatectomy. The median (IQR) annual hospital volume for pancreatoduodenectomy was 36 (28-44). Out of 19 centers, 17 performed ≥20 and 4 centers performed ≥40 pancreatoduodenectomies annually. Two low-volume hospitals stopped pancreatic surgery. Nationwide in-hospital mortality decreased from 3.6% to 2.8% (OR 0.65, 95%CI 0.43-0.98, p=0.04). Failure to rescue improved from 12.8% to 10.2% (OR 0.61, 95%CI 0.40-0.95, p=0.03). The rates of textbook outcome (59.0%), postoperative pancreatic fistula (ISGPS B/C, 14.8%), readmission (16.7%), and median hospital stay (11 days) did not change significantly. The use of neoadjuvant therapy (5.8% vs 10.4%, p<0.01) and minimally invasive pancreatoduodenectomy (6.7% vs 20.5%, p<0.01) increased whereas the use of adjuvant therapy (67.3%) did not change. Conclusion: Considerable changes were noted in the first four years of the DPCA, including improved in-hospital mortality and failure to rescue rates, and increased use of neoadjuvant therapy and minimally invasive pancreatoduodenectomy.

Prognostic Factors Associated with Long-Term Recurrence-Free Survival after Resection of Pancreatic Ductal Adenocarcinoma (PDAC): A Nationwide Analysis

Introduction: About 80% of patients undergoing PDAC resection develop disease recurrence within two years after surgery, contributing to poor survival rates. However, 20% of patients do have long-term recurrence-free survival (RFS). In this study, we aimed to identify prognostic factors associated with an RFS of 2-3 years, 3-5 years or >5 years after PDAC resection. Method: This national cohort study includes all patients who underwent PDAC resection in the Netherlands between 2014-2016. Data was collected prospectively from the Dutch Pancreatic Cancer Audit and retrospectively from the patients’ records. Patients were divided into four groups based on RFS: <2 years (reference group), 2-3 years, 3-5 years and >5 years. Prognostic factors were determined by multinomial regression analysis. Results: A total of 836 patients with a median follow-up of 46 (interquartile range (IQR) 34-58) months and median survival of 20 (IQR 11-36) months were analyzed. Information on RFS was available in 627 patients: 485 patients (77%) had an RFS of <2 years, 75 patients (15%) of 2-3 years, 33 patients (5%) of 3-5 years and 34 patients (5%) of >5 years. Further results are shown in Table 1. Conclusions: A well/moderately differentiated tumor and R0 (≥1 mm) resection margin status are related to an RFS of 3-5 years. Fewer positive lymph nodes are associated with an RFS of 3-5 and >5 years. These prognostic factors can be useful in estimating the long-term prognosis for patients and contribute to individualized follow-up and treatment strategies.Tabled 1FP19-4Table 1. Results of 627 patients who underwent PDAC resection between 2014 and 2016 (excluding patients with irradical resection or complication-related mortality within 90 days postoperatively)Recurrence-free survival*2-3 years1. years> 5 yearsOR**95% CIP-valueOR**95% CIP-valueOR**95% CIP-valueDifferentiation (well/moderate vs. poor/undifferentiated)1.780.98-3.220.0572.821.09-7.340.0331.090.48-2.480.830Number of positive lymph nodes (continuous)1.030.94-1.130.4941.321.08-1.610.0061.571.20-2.05<0.001Resection margin status (R0 ≥ 1 mm vs. R1 < 1 mm)1.200.70-2.060.5083.431.45-8.090.0051.630.74-3.630.228Adjuvant chemotherapy (yes vs. no)2.991.56-5.72<0.0012.450.99-6.050.0521.350.57-3.170.498PDAC: pancreatic ductal adenocarcinoma; OR: odds ratio; CI: confidence interval. * Compared to the reference group with a recurrence-free survival of <2 years. ** Multinomial regression analysis corrected for gender, CACI-score, neoadjuvant therapy, preoperative CA 19-9 value, tumor location, vascular resection, diameter of the tumor, tumor differentiation, lymphovascular invasion, neural invasion, number of positive lymph nodes, resection margin status, major complications, and adjuvant chemotherapy. In case of a continuous variable, 1 unit decrease of the relevant variable is related to the corresponding odds ratio. Open table in a new tab PDAC: pancreatic ductal adenocarcinoma; OR: odds ratio; CI: confidence interval. * Compared to the reference group with a recurrence-free survival of <2 years. ** Multinomial regression analysis corrected for gender, CACI-score, neoadjuvant therapy, preoperative CA 19-9 value, tumor location, vascular resection, diameter of the tumor, tumor differentiation, lymphovascular invasion, neural invasion, number of positive lymph nodes, resection margin status, major complications, and adjuvant chemotherapy. In case of a continuous variable, 1 unit decrease of the relevant variable is related to the corresponding odds ratio.

Incidence of and Risk Factors for Chyle Leak after Pancreatic Resection: A Nationwide Analysis

Introduction: In 2017 the International Study Group for Pancreatic Surgery (ISGPS) published a consensus definition of chyle leak (CL). Multicenter series assessing the ISGPS-CL definition are lacking and previous studies investigating risk factors for CL used different definitions and showed heterogeneous results. The aim of this study was to assess the clinical impact of the ISGPS-CL definition on incidence, the association with length of stay and mortality, and to assess risk factors of CL. Method: This observational cohort study included patients who underwent pancreatoduodenectomy from the mandatory nationwide Dutch Pancreatic Cancer Audit (2017-2019). Only clinically relevant CL (grade B/C) was included. Prolonged length of stay was defined as more than 14 days. Multivariable logistic regression models were performed. Results: Overall, 2159 patients after pancreatoduodenectomy were included. The rate of CL was 7.0% (n=152), including 6.9% (n=150) grade B and 0.1% (n=2) grade C. After adjustment for confounders, CL was associated with a prolonged hospital stay (OR 2.84, 95% CI 1.85-4.36, p < 0.001). In multivariable analysis, CL was not related to in-hospital mortality. Vascular resection, i.e. arterial and/or venous resections (OR 2.1, 95% CI 1.4-3.2, p < 0.001) and open surgery (OR 3.5, 95% CI 1.7-7.2, p = 0.001) were identified as independent predictors for CL in multivariable analyses, whereas the number of lymph nodes resected and aortocaval lymph node sampling was not. Conclusion: Use of the ISGPS-CL definition is recommended for further studies, to adequately compare results. Risk factors should be taken into account in the postoperative follow-up.

P-P53 Textbook outcomes in pancreatoduodenectomy are improved in high volume specialist pancreas-only centres

Abstract Background Traditional single surgical quality indicators are commonly used however they are poor for assessing global outcomes for patients. Composite outcomes such as the ‘Textbook Outcome’ (TO) is a composite outcome to determine the success of the quality of the surgical process, and compare outcomes between institutions and patient groups, described by the Dutch Pancreatic Cancer Audit Group for Pancreatoduodenectomy (PD). They reported national TOs for PD of 58.3%, we compared this to TOs in a UK high volume specialist pancreas-only centre, Royal Stoke. Methods Patients who underwent PD from January 2017 to December 2020 were identified from our database. TO was defined as absence the following: post-operative pancreatic fistula (POPF) (grade B/C), post-pancreatectomy haemorrhage (PPH), bile leak, severe complications (Clavien Dindo grade III or more), 30-day readmission and 30-day mortality. Results 153 patients underwent PD during the 4-year study period. The median age was 71years (range 37-85 years), and there was a slight male preponderance (54.9%, 84/153). 47% had pancreatic ductal adenocarcinoma (72/153), 17% ampullary carcinoma (26/153), 9% cholangiocarcinoma (14/153), 9% duodenal carcinoma (14/153), and benign pathology included cases with IPMN and duodenal polyps with high grade dysplasia. There was a statistically significant difference in textbook outcome in our cohort compared to the Dutch Study (70.3%, 108/153 vs 58.3%, 895/1536; p=0.003086), with components of TO shown in Figure 1. Conclusions TO represent composite outcome for identifying good practice, areas for shared learning and areas for improvement. PD performed in high-volume pancreas-only specialist centers appear to have better outcomes following PD than lower-volume centres. Further investigation is required to assess why outcomes are different between centres, and identify how best practice can be shared.

The Costs of Complications and Unplanned Readmissions after Pancreatoduodenectomy for Pancreatic and Periampullary Tumors: Results from a Single Academic Center

Simple SummaryComplications lead to unplanned readmissions (UR) and are reported to be associated with a two- to threefold increase in hospital admission costs. Since healthcare costs are increasing worldwide, cost containment is the major challenge for future healthcare. In the literature, there are only a few studies that analysed hospital costs after pancreatoduodenectomy (PD). In this study, we aimed to create an understanding of the costs of complications and UR in patients who underwent a PD.Background/Objectives: Complications after pancreatoduodenectomy (PD) lead to unplanned readmissions (UR), with a two- to threefold increase in admission costs. In this study, we aimed to create an understanding of the costs of complications and UR in this patient group. Furthermore, we aimed to generate a detailed cost overview that can be used to build a theoretical model to calculate the cost efficacy for prehabilitation. Methods: A retrospective cohort analysis was performed using the Dutch Pancreatic Cancer Audit (DPCA) database of patients who underwent a PD at our institute between 2013 and 2017. The total costs of the index hospital admission and UR related to the PD were collected. Results: Of the 160 patients; 35 patients (22%) had an uncomplicated course; 87 patients (54%) had minor complications, and 38 patients (24%) had severe complications. Median costs for an uncomplicated course were EUR 25.682, and for a complicated course, EUR 32.958 (p = 0.001). The median costs for minor complications were EUR 30.316, and for major complications, EUR 42.664 (p = 0.001). Costs were related to the Comprehensive Complication Index (CCI). The median costs of patients with one or more UR were EUR 41.199. Conclusions: Complications after PD led to a EUR 4.634–EUR 16.982 (18–66%) increase in hospital costs. A UR led to a cost increase of EUR 12.567 (44%). Since hospital costs are directly related to the CCI, reduction in complications will lead to cost-effectiveness.

Outcome of pancreatic anastomoses during pancreatoduodenectomy in two national audits

BackgroundEvidence on the optimal pancreatic anastomosis during pancreatoduodenectomy is inconclusive. Large multicenter and nationwide registries may provide additional insights. The study compared the practice and outcome of different pancreatic anastomoses during pancreatoduodenectomy, focusing on the rate of postoperative pancreatic fistula, in two large audits of pancreatic surgery. MethodsPosthoc analysis of patients after pancreatoduodenectomy in the Dutch Pancreatic Cancer Audit and the German DGAV StuDoQ|Pancreas registries (January 2014 to December 2017). Postoperative pancreatic fistula (International Study Group of Pancreatic Surgery B/C), postpancreatectomy hemorrhage (International Study Group of Pancreatic Surgery B/C) and Clavien-Dindo ≥3 complications rates were compared for the three most common anastomoses: duct-to-mucosa pancreatojejunostomy, non-duct-to-mucosa pancreatojejunostomy, and non-duct-to-mucosa pancreatogastrostomy. Multivariable adjustment for potential confounders was performed. ResultsOverall, 6,149 patients were included. The most common anastomosis was duct-to-mucosa pancreatojejunostomy (duct-to-mucosa pancreatojejunostomy 59.8%, non-duct-to-mucosa pancreatojejunostomy 21.1%, non-duct-to-mucosa pancreatogastrostomy 12.4%). The overall postoperative pancreatic fistula rate was 14%: duct-to-mucosa pancreatojejunostomy 12.9%, non-duct-to-mucosa pancreatojejunostomy 14.4% (P = .162), non-duct-to-mucosa pancreatogastrostomy 18.3% (P < .001). The rate of postpancreatectomy hemorrhage was the lowest after duct-to-mucosa pancreatojejunostomy: duct-to-mucosa pancreatojejunostomy 6.9%, non-duct-to-mucosa pancreatojejunostomy 10% (P < .001), non-duct-to-mucosa pancreatogastrostomy 17.9% (P < .001). The rate of Clavien-Dindo ≥3 complications was the lowest after duct-to-mucosa pancreatojejunostomy: duct-to-mucosa pancreatojejunostomy 28%, non-duct-to-mucosa pancreatojejunostomy 32.7% (P = .002), non-duct-to-mucosa pancreatogastrostomy 43.1% (P < .001). In the multivariable analysis, the risk of postoperative pancreatic fistula did not differ significantly between the three anastomoses. The risk of hemorrhage (odds ratio 2.4, 95% confidence interval 1.6–3.5, P < .001) and Clavien-Dindo ≥3 (odds ratio 1.6, 95% confidence interval 1.2–2.1, P = .001) remained significantly higher only for non-duct-to-mucosa pancreatogastrostomy. ConclusionData from two national audits showed no difference in the risk-adjusted postoperative pancreatic fistula rate among the three most used pancreatic anastomoses during pancreatoduodenectomy. Pancreatogastrostomy was inferior to pancreatojejunostomy regarding bleeding and overall major complications.

Preoperative misdiagnosis of pancreatic and periampullary cancer in patients undergoing pancreatoduodenectomy: A multicentre retrospective cohort study

IntroductionWhereas neoadjuvant chemo(radio)therapy is increasingly used in pancreatic cancer, it is currently not recommended for other periampullary (non-pancreatic) cancers. This has important implications for the relevance of the preoperative diagnosis for pancreatoduodenectomy. This retrospective multicentre cohort study aimed to determine the frequency of clinically relevant misdiagnoses in patients undergoing pancreatoduodenectomy for pancreatic or other periampullary cancer. MethodsData from all consecutive patients who underwent a pancreatoduodenectomy between 2014 and 2018 were obtained from the prospective Dutch Pancreatic Cancer Audit. The preoperative diagnosis as concluded by the multidisciplinary team (MDT) meeting was compared with the final postoperative diagnosis at pathology to determine the rate of clinically relevant misdiagnosis (defined as missed pancreatic cancer or incorrect diagnosis of pancreatic cancer). ResultsIn total, 1244 patients underwent pancreatoduodenectomy of whom 203 (16%) had a clinically relevant misdiagnosis preoperatively. Of all patients with a final diagnosis of pancreatic cancer, 13% (87/679) were preoperatively misdiagnosed as distal cholangiocarcinoma (n = 41, 6.0%), ampullary cancer (n = 27, 4.0%) duodenal cancer (n = 16, 2.4%), or other (n = 3, 0.4%). Of all patients with a final diagnosis of periampullary (non-pancreatic) cancer, 21% (116/565) were preoperatively incorrectly diagnosed as pancreatic cancer. Accuracy of preoperative diagnosis was 84% for pancreatic cancer, 71% for distal cholangiocarcinoma, 73% for ampullary cancer and 73% for duodenal cancer. A prediction model for the preoperative likelihood of pancreatic cancer (versus other periampullary cancer) prior to pancreatoduodenectomy demonstrated an AUC of 0.88. DiscussionThis retrospective multicentre cohort study showed that 16% of patients have a clinically relevant misdiagnosis that could result in either missing the opportunity of neoadjuvant chemotherapy in patients with pancreatic cancer or inappropriate administration of neoadjuvant chemotherapy in patients with non-pancreatic periampullary cancer. A preoperative prediction model is available on www.pancreascalculator.com.

First four Years of a Nationwide Audit: Did Clinical Practice and Outcomes in Pancreatic Surgery Improve?

Purpose: The Dutch Pancreatic Cancer Audit (DPCA) was established to monitor and improve nationwide outcomes of pancreatic surgery. This study aimed to describe changes in clinical practice and outcomes of pancreatic surgery in the first four years of the DPCA. Methods: Consecutive patients who underwent pancreatoduodenectomy or distal pancreatectomy were registered in the nationwide, mandatory DPCA. Results were analyzed in two time periods (2014-2015 and 2016-2017). Trends in patient, tumor and treatment characteristics were assessed using univariable regression analyses. Short-term surgical outcomes were investigated using multilevel multivariable logistic regression analyses. Results: Out of 3508 patients, 2780 (79.2%) underwent pancreatoduodenectomy and 728 (20.8%) distal pancreatectomy. The median (IQR) annual hospital volume for pancreatoduodenectomy was 36 (28-44). Out of 19 centers, 17 performed ≥20 and 4 centers performed ≥40 pancreatoduodenectomies in every year. Two low-volume hospitals stopped pancreatic surgery. Nationwide in-hospital mortality decreased from 3.6% to 2.8% (p=0.04; OR 0.65; 95%CI 0.43-0.98). Failure to rescue improved from 12.8% to 10.2% (p=0.03; OR 0.61; 95%CI 0.40-0.95). The rates of textbook outcome (59.0%), postoperative pancreatic fistula (ISGPS-B/C, 14.8%), readmission (16.7%), and median hospital stay (11 days) did not change significantly. The use of neoadjuvant therapy (5.8% vs 10.4%, p<0.01) and minimally invasive pancreatoduodenectomy (6.7% vs 20.5%, p<0.01) increased whereas the use of adjuvant therapy (67.3%) did not change significantly. Conclusion: Considerable changes were noted in the first four years of the DPCA: in-hospital mortality and failure to rescue rates improve whereas the use of neoadjuvant therapy and minimally invasive pancreatoduodenectomy increased.

Somatostatin Analogues for the Prevention of Pancreatic Fistula after Open Pancreatoduodenectomy: A Nationwide Analysis

Purpose: Somatostatin analogues (SA) are varyingly used to try to prevent development of a pancreatic postoperative fistula (POPF) after pancreatoduodenectomy. Some centers do not use SA, some use it only in high-risk patients, and others in all patients. The aim of this study was to evaluate the effect of different protocols for SA use on the incidence of POPF after pancreatoduodenectomy in the Netherlands. Method: The Dutch Pancreatic Cancer Audit (DPCA) is a national, mandatory audit that registers all patients after pancreatoduodenectomy. Consecutive patients undergoing elective open pancreatoduodenectomy for all indications were included from the DPCA (2014-2017). Patients were divided into six groups depending on the SA protocol: no SA, octreotide, lanreotide, pasireotide, octreotide only in high risk patients, and lanreotide only in high risk patients. Primary endpoint was POPF (grade B and C). The updated alternative Fistula Risk Score (uaFRS) was used to analyze the occurrence of clinically relevant POPF across various risk scenarios (low-intermediate risk (<20%) and high risk (≥20%)). Results: Overall, 1992 patients were included with a POPF rate of 13.1%. POPF occurred less often when octreotide was administered in high risk patients only (9.4%) or if a lanreotide protocol was used (10.0%) compared to other protocols (varying from 12.7-19.1%, p=0.001). Sub-analysis in 577 patients (56.7%) with a high uaFRS showed a significantly lower rate of POPF when treated with lanreotide (10.0%) compared to the other protocols (varying from 18.9%-27.4%) (p=<0.001). In the 440 patients (43.3%) with a low-intermediate uaFRS the rate of POPF did not differ significantly between the six protocols. Multivariate regression analysis, controlling for male sex, BMI, soft pancreatic tissue, a pancreatic duct smaller than 3mm, ASA score III/IV, neuroendocrine tumor pathology, demonstrated lanreotide to be significantly associated with a low OR for POPF (OR 0.387, 95% CI 0.180-0.834) compared to no SA use. Conclusion: This nationwide retrospective study suggests that the use of lanreotide in patients undergoing pancreatoduodenectomy is beneficial in reducing the rate of POPF. However, perioperative mortality is unaffected. Since SA appear not to be beneficial in low-intermediate risk patients, the use of lanreotide may be reserved for patients at high risk of POPF.