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Contains fulltext : 305021.pdf (Publisher’s version ) (Closed access), OBJECTIVE: This nationwide multicenter study aimed to define clinically relevant thresholds of relative serum CA19-9 response after 2 months of induction chemotherapy in patients with locally advanced pancreatic cancer (LAPC). BACKGROUND: CA19-9 is seen as leading biomarker for response evaluation in patients with LAPC, but early clinically useful cut-offs are lacking. METHODS: All consecutive patients with LAPC after 4 cycles (m)FOLFIRINOX or 2 cycles gemcitabine-nab-paclitaxel induction chemotherapy (±radiotherapy) with CA19-9 ≥5 U/mL at baseline were analyzed (2015-2019). The association of CA19-9 response with median OS (mOS) was evaluated for different CA19-9 cut-off points. Minimum and optimal CA19-9 response were established via log-rank test. Predictors for OS were analyzed using COX regression analysis. RESULTS: Overall, 212 patients were included, of whom 42 (19.8%) underwent resection. Minimum CA19-9 response demonstrating a clinically significant median OS difference (12.7 vs. 19.6 months) was seen at ≥40% CA19-9 decrease. The optimal cutoff for CA19-9 response was ≥60% decrease (21.7 vs. 14.0 mo, P =0.021). Only for patients with elevated CA19-9 levels at baseline (n=184), CA19-9 decrease ≥60% [hazard ratio (HR)=0.59, 95% CI, 0.36-0.98, P =0.042] was independently associated with prolonged OS, as were SBRT (HR=0.42, 95% CI, 0.25-0.70; P =0.001), and resection (HR=0.25, 95% CI, 0.14-0.46, P <0.001), and duration of chemotherapy (HR=0.75, 95% CI, 0.69-0.82, P <0.001). CONCLUSIONS: CA19-9 decrease of ≥60% following induction chemotherapy as optimal response cut-off in patients with LAPC is an independent predictor for OS when CA19-9 is increased at baseline. Furthermore, ≥40% is the minimum cut-off demonstrating survival benefit. These cut-offs may be used when discussing treatment strategies during early response evaluation.

Item does not contain fulltext, BACKGROUND: The causal pathway between complications after pancreatic cancer resection and impaired long-term survival remains unknown. The aim of this study was to investigate the impact of complications after pancreatic cancer resection on disease-free interval and overall survival, with adjuvant chemotherapy as a mediator. METHODS: This observational study included all patients undergoing pancreatic cancer resection in the Netherlands (2014-2017). Clinical data were extracted from the prospective Dutch Pancreatic Cancer Audit. Recurrence and survival data were collected additionally. In causal mediation analysis, direct and indirect effect estimates via adjuvant chemotherapy were calculated. RESULTS: In total, 1071 patients were included. Major complications (hazards ratio 1.22 (95 per cent c.i. 1.04 to 1.43); P = 0.015 and hazards ratio 1.25 (95 per cent c.i. 1.08 to 1.46); P = 0.003) and organ failure (hazards ratio 1.86 (95 per cent c.i. 1.32 to 2.62); P < 0.001 and hazards ratio 1.89 (95 per cent c.i. 1.36 to 2.63); P < 0.001) were associated with shorter disease-free interval and overall survival respectively. The effects of major complications and organ failure on disease-free interval (-1.71 (95 per cent c.i. -2.27 to -1.05) and -3.05 (95 per cent c.i. -4.03 to -1.80) respectively) and overall survival (-1.92 (95 per cent c.i. -2.60 to -1.16) and -3.49 (95 per cent c.i. -4.84 to -2.03) respectively) were mediated by adjuvant chemotherapy. Additionally, organ failure directly affected disease-free interval (-5.38 (95 per cent c.i. -9.27 to -1.94)) and overall survival (-6.32 (95 per cent c.i. -10.43 to -1.99)). In subgroup analyses, the association was found in patients undergoing pancreaticoduodenectomy, but not in patients undergoing distal pancreatectomy. CONCLUSION: Major complications, including organ failure, negatively impact survival in patients after pancreatic cancer resection, largely mediated by adjuvant chemotherapy. Prevention or adequate trea

01 april 2023, Item does not contain fulltext, BACKGROUND: Large inter-surgeon variability exists in technical anatomical resectability assessment of colorectal cancer liver-only metastases (CRLM) following induction systemic therapy. We evaluated the role of tumour biological factors in predicting resectability and (early) recurrence after surgery for initially unresectable CRLM. METHODS: 482 patients with initially unresectable CRLM from the phase 3 CAIRO5 trial were selected, with two-monthly resectability assessments by a liver expert panel. If no consensus existed among panel surgeons (i.e. same vote for (un)resectability of CRLM), conclusion was based on majority. The association of tumour biological (sidedness, synchronous CRLM, carcinoembryonic antigen and RAS/BRAF(V600E) mutation status) and technical anatomical factors with consensus among panel surgeons, secondary resectability and early recurrence (<6 months) without curative-intent repeat local treatment was analysed by uni- and pre-specified multivariable logistic regression. RESULTS: After systemic treatment, 240 (50%) patients received complete local treatment of CRLM of which 75 (31%) patients experienced early recurrence without repeat local treatment. Higher number of CRLM (odds ratio 1.09 [95% confidence interval 1.03-1.15]) and age (odds ratio 1.03 [95% confidence interval 1.00-1.07]) were independently associated with early recurrence without repeat local treatment. In 138 (52%) patients, no consensus among panel surgeons was present prior to local treatment. Postoperative outcomes in patients with and without consensus were comparable. CONCLUSIONS: Almost a third of patients selected by an expert panel for secondary CRLM surgery following induction systemic treatment experience an early recurrence only amenable to palliative treatment. Number of CRLM and age, but no tumour biological factors are predictive, suggesting that until there are better biomarkers; resectability assessment remains primarily a technical anatomical decision.

Item does not contain fulltext, OBJECTIVE: To establish an evidence-based cutoff and predictors for early recurrence in patients with resected locally advanced pancreatic cancer (LAPC). BACKGROUND: It is unclear how many and which patients develop early recurrence after LAPC resection. Surgery in these patients is probably of little benefit. METHODS: We analyzed all consecutive patients undergoing resection of LAPC after induction chemotherapy who were included in prospective databases in The Netherlands (2015-2019) and the Johns Hopkins Hospital (2016-2018). The optimal definition for "early recurrence" was determined by the post-recurrence survival (PRS). Patients were compared for overall survival (OS). Predictors for early recurrence were evaluated using logistic regression analysis. RESULTS: Overall, 168 patients were included. After a median follow-up of 28 months, recurrence was observed in 118 patients (70.2%). The optimal cutoff for recurrence-free survival to differentiate between early (n=52) and late recurrence (n=66) was 6 months ( P <0.001). OS was 8.4 months [95% confidence interval (CI): 7.3-9.6] in the early recurrence group (n=52) versus 31.1 months (95% CI: 25.7-36.4) in the late/no recurrence group (n=116) ( P <0.001). A preoperative predictor for early recurrence was postinduction therapy carbohydrate antigen (CA) 19-9≥100 U/mL [odds ratio (OR)=4.15, 95% CI: 1.75-9.84, P =0.001]. Postoperative predictors were poor tumor differentiation (OR=4.67, 95% CI: 1.83-11.90, P =0.001) and no adjuvant chemotherapy (OR=6.04, 95% CI: 2.43-16.55, P <0.001). CONCLUSIONS: Early recurrence was observed in one third of patients after LAPC resection and was associated with poor survival. Patients with post-induction therapy CA 19-9 ≥100 U/mL, poor tumor differentiation and no adjuvant therapy were especially at risk. This information is valuable for patient counseling before and after resection of LAPC.

Item does not contain fulltext, BACKGROUND: The International Study Group of Pancreatic Surgery 4-tier (ie, A-D) risk classification for postoperative pancreatic fistula grade B/C is based on pancreatic texture and pancreatic duct size: A (not-soft texture and pancreatic duct >3 mm), B (not-soft texture and pancreatic duct ≤3 mm), C (soft texture and pancreatic duct >3 mm), and D (soft texture and pancreatic duct ≤3 mm). This study aimed to validate the International Study Group of Pancreatic Surgery risk classification for postoperative pancreatic fistula after pancreatoduodenectomy. METHODS: Consecutive patients after pancreatoduodenectomy for all indications (2014-2021) were included from the nationwide, mandatory Dutch Pancreatic Cancer Audit. The rate of postoperative pancreatic fistula grade B/C (according to the International Study Group of Pancreatic Surgery 2016 definition) was calculated per risk category. Model performance was assessed using the area under the receiver operating curve (discrimination) and calibration plots. RESULTS: Overall, 3,900 patients were included in risk categories: A (n = 1,046), B (n = 498), C (n = 963), and D (n = 1,393) with corresponding postoperative pancreatic fistula grade B/C rates of 3.8%, 12.2%, 15.6%, and 29.6%. Per category, the in-hospital mortality rates were 1.3%, 3.4%, 2.9%, and 4.1%, P = .001. There was no difference in the rate of postoperative pancreatic fistula between risk categories B and C (12.2% vs 15.6%, P = .101). When simplifying the classification system to a 3-tier classification system (based on 0, 1, and 2 risk factors), the discrimination was not significantly different (area under the receiver operating curve 0.697 vs area under the receiver operating curve 0.701, P = .077). CONCLUSION: This validation of the 4-tier International Study Group of Pancreatic Surgery risk classification for postoperative pancreatic fistula after pancreatoduodenectomy confirmed its predictive value. However, as the 2 middle risk categories provide no

01 april 2023, Item does not contain fulltext, BACKGROUND: Surgical 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. METHODS: After 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. RESULTS: Overall, 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). CONCLUSION: Pancreatoduodenectomy 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

Contains fulltext : 296536.pdf (Publisher’s version ) (Closed access), IMPORTANCE: Understanding the learning curve of a new complex surgical technique helps to reduce potential patient harm. Current series on the learning curve of minimally invasive distal pancreatectomy (MIDP) are mostly small, single-center series, thus providing limited data. OBJECTIVE: To evaluate the length of pooled learning curves of MIDP in experienced centers. DESIGN, SETTING, AND PARTICIPANTS: This international, multicenter, retrospective cohort study included MIDP procedures performed from January 1, 2006, through June 30, 2019, in 26 European centers from 8 countries that each performed more than 15 distal pancreatectomies annually, with an overall experience exceeding 50 MIDP procedures. Consecutive patients who underwent elective laparoscopic or robotic distal pancreatectomy for all indications were included. Data were analyzed between September 1, 2021, and May 1, 2022. EXPOSURES: The learning curve for MIDP was estimated by pooling data from all centers. MAIN OUTCOMES AND MEASURES: The learning curve was assessed for the primary textbook outcome (TBO), which is a composite measure that reflects optimal outcome, and for surgical mastery. Generalized additive models and a 2-piece linear model with a break point were used to estimate the learning curve length of MIDP. Case mix-expected probabilities were plotted and compared with observed outcomes to assess the association of changing case mix with outcomes. The learning curve also was assessed for the secondary outcomes of operation time, intraoperative blood loss, conversion to open rate, and postoperative pancreatic fistula grade B/C. RESULTS: From a total of 2610 MIDP procedures, the learning curve analysis was conducted on 2041 procedures (mean [SD] patient age, 58 [15.3] years; among 2040 with reported sex, 1249 were female [61.2%] and 791 male [38.8%]). The 2-piece model showed an increase and eventually a break point for TBO at 85 procedures (95% CI, 13-157 procedures), with a plateau TBO rate at

01 september 2023, Contains fulltext : 295971.pdf (Publisher’s version ) (Open Access), BACKGROUND: Consensus on resectability criteria for colorectal cancer liver metastases (CRLM) is lacking, resulting in differences in therapeutic strategies. This study evaluated variability of resectability assessments and local treatment plans for patients with initially unresectable CRLM by the liver expert panel from the randomised phase III CAIRO5 study. METHODS: The liver panel, comprising surgeons and radiologists, evaluated resectability by predefined criteria at baseline and 2-monthly thereafter. If surgeons judged CRLM as resectable, detailed local treatment plans were provided. The panel chair determined the conclusion of resectability status and local treatment advice, and forwarded it to local surgeons. RESULTS: A total of 1149 panel evaluations of 496 patients were included. Intersurgeon disagreement was observed in 50% of evaluations and was lower at baseline than follow-up (36% vs. 60%, p < 0.001). Among surgeons in general, votes for resectable CRLM at baseline and follow-up ranged between 0-12% and 27-62%, and for permanently unresectable CRLM between 3-40% and 6-47%, respectively. Surgeons proposed different local treatment plans in 77% of patients. The most pronounced intersurgeon differences concerned the advice to proceed with hemihepatectomy versus parenchymal-preserving approaches. Eighty-four percent of patients judged by the panel as having resectable CRLM indeed received local treatment. Local surgeons followed the technical plan proposed by the panel in 40% of patients. CONCLUSION: Considerable variability exists among expert liver surgeons in assessing resectability and local treatment planning of initially unresectable CRLM. This stresses the value of panel-based decisions, and the need for consensus guidelines on resectability criteria and technical approach to prevent unwarranted variability in clinical practice.

Contains fulltext : 296781.pdf (Publisher’s version ) (Open Access), BACKGROUND: Practice variation exists in venous resection during pancreatoduodenectomy, but little is known about the potential causes and consequences as large studies are lacking. This study explores the potential causes and consequences of practice variation in venous resection during pancreatoduodenectomy for pancreatic cancer in the Netherlands. METHODS: This nationwide retrospective cohort study included patients undergoing pancreatoduodenectomy for pancreatic cancer in 18 centers from 2013 through 2017. RESULTS: Among 1,311 patients undergoing pancreatoduodenectomy, 351 (27%) had a venous resection, and the overall median annual center volume of venous resection was 4. No association was found between the center volume of pancreatoduodenectomy and the rate of venous resections, nor between patient and tumor characteristics and the rate of venous resections per center. Female sex, lower body mass index, neoadjuvant therapy, venous involvement, and stenosis on imaging were predictive for venous resection. Adjusted for these factors, 3 centers performed significantly more, and 3 centers performed significantly fewer venous resections than expected. In patients with venous resection, significantly less major morbidity (22% vs 38%) and longer overall survival (median 16 vs 12 months) were observed in centers with an above-median annual volume of venous resections (>4). CONCLUSION: Patient and tumor characteristics did not explain significant practice variation between centers in the Netherlands in venous resection during pancreatoduodenectomy for pancreatic cancer. The clinical outcomes of venous resection might be related to the volume of the procedure.

Item does not contain fulltext, INTRODUCTION: Necrotizing pancreatitis may result in a disrupted or disconnected pancreatic duct (DPD) with the potential for long-lasting negative impact on a patient's clinical outcome. There is a lack of detailed data on the full clinical spectrum of DPD, which is critical for the development of better diagnostic and treatment strategies. METHODS: We performed a long-term post hoc analysis of a prospectively collected nationwide cohort of 896 patients with necrotizing pancreatitis (2005-2015). The median follow-up after hospital admission was 75 months (P25-P75: 41-151). Clinical outcomes of patients with and without DPD were compared using regression analyses, adjusted for potential confounders. Predictive features for DPD were explored. RESULTS: DPD was confirmed in 243 (27%) of the 896 patients and resulted in worse clinical outcomes during both the patient's initial admission and follow-up. During hospital admission, DPD was associated with an increased rate of new-onset intensive care unit admission (adjusted odds ratio [aOR] 2.52; 95% confidence interval [CI] 1.62-3.93), new-onset organ failure (aOR 2.26; 95% CI 1.45-3.55), infected necrosis (aOR 4.63; 95% CI 2.87-7.64), and pancreatic interventions (aOR 7.55; 95% CI 4.23-13.96). During long-term follow-up, DPD increased the risk of pancreatic intervention (aOR 9.71; 95% CI 5.37-18.30), recurrent pancreatitis (aOR 2.08; 95% CI 1.32-3.29), chronic pancreatitis (aOR 2.73; 95% CI 1.47-5.15), and endocrine pancreatic insufficiency (aOR 1.63; 95% CI 1.05-2.53). Central or subtotal pancreatic necrosis on computed tomography (OR 9.49; 95% CI 6.31-14.29) and a high level of serum C-reactive protein in the first 48 hours after admission (per 10-point increase, OR 1.02; 95% CI 1.00-1.03) were identified as independent predictors for developing DPD. DISCUSSION: At least 1 of every 4 patients with necrotizing pancreatitis experience DPD, which is associated with detrimental, short-term and long-term interventions, and

Item does not contain fulltext, OBJECTIVE: To develop a fistula risk score for auditing, to be able to compare postoperative pancreatic fistula (POPF) after pancreatoduodenectomy among hospitals. BACKGROUND: For proper comparisons of outcomes in surgical audits, case-mix variation should be accounted for. METHODS: 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. RESULTS: 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. CONCLUSIONS: The auditing fistula risk score was successful in case-mix adjustment and enables fair comparisons of POPF rates among hospitals.

01 juli 2023, Item does not contain fulltext, BACKGROUND: Patients with initially unresectable colorectal cancer liver metastases might qualify for local treatment with curative intent after reducing the tumour size by induction systemic treatment. We aimed to compare the currently most active induction regimens. METHODS: In this open-label, multicentre, randomised, phase 3 study (CAIRO5), patients aged 18 years or older with histologically confirmed colorectal cancer, known RAS/BRAF(V600E) mutation status, WHO performance status of 0-1, and initially unresectable colorectal cancer liver metastases were enrolled at 46 Dutch and one Belgian secondary and tertiary centres. Resectability or unresectability of colorectal cancer liver metastases was assessed centrally by an expert panel of liver surgeons and radiologists, at baseline and every 2 months thereafter by predefined criteria. Randomisation was done centrally with the minimisation technique via a masked web-based allocation procedure. Patients with right-sided primary tumour site or RAS or BRAF(V600E) mutated tumours were randomly assigned (1:1) to receive FOLFOX or FOLFIRI plus bevacizumab (group A) or FOLFOXIRI plus bevacizumab (group B). Patients with left-sided and RAS and BRAF(V600E) wild-type tumours were randomly assigned (1:1) to receive FOLFOX or FOLFIRI plus bevacizumab (group C) or FOLFOX or FOLFIRI plus panitumumab (group D), every 14 days for up to 12 cycles. Patients were stratified by resectability of colorectal cancer liver metastases, serum lactate dehydrogenase concentration, choice of irinotecan versus oxaliplatin, and BRAF(V600E) mutation status (for groups A and B). Bevacizumab was administered intravenously at 5 mg/kg. Panitumumab was administered intravenously at 6 mg/kg. FOLFIRI consisted of intravenous infusion of irinotecan at 180 mg/m(2) with folinic acid at 400 mg/m(2), followed by bolus fluorouracil at 400 mg/m(2) intravenously, followed by continuous infusion of fluorouracil at 2400 mg/m(2). FOLFOX consisted of oxaliplatin at

Item does not contain fulltext, OBJECTIVE: The aim of this study was to explore the incidence, risk factors, clinical course and treatment of perforation and fistula of the gastrointestinal (GI) tract in a large unselected cohort of patients with necrotizing pancreatitis. BACKGROUND: Perforation and fistula of the GI tract may occur in necrotizing pancreatitis. Data from large unselected patient populations on the incidence, risk factors, clinical outcomes, and treatment are lacking. METHODS: We performed a post hoc analysis of a nationwide prospective database of 896 patients with necrotizing pancreatitis. GI tract perforation and fistula were defined as spontaneous or iatrogenic discontinuation of the GI wall. Multivariable logistic regression was used to explore risk factors and to adjust for confounders to explore associations of the GI tract perforation and fistula on the clinical course. RESULTS: A perforation or fistula of the GI tract was identified in 139 (16%) patients, located in the stomach in 23 (14%), duodenum in 56 (35%), jejunum or ileum in 18 (11%), and colon in 64 (40%). Risk factors were high C-reactive protein within 48 hours after admission [odds ratio (OR): 1.19; 95% confidence interval (CI): 1.01-1.39] and early organ failure (OR: 2.76; 95% CI: 1.78-4.29). Prior invasive intervention was a risk factor for developing a perforation or fistula of the lower GI tract (OR: 2.60; 95% CI: 1.04-6.60). While perforation or fistula of the upper GI tract appeared to be protective for persistent intensive care unit-admission (OR: 0.11, 95% CI: 0.02-0.44) and persistent organ failure (OR: 0.15; 95% CI: 0.02-0.58), perforation or fistula of the lower GI tract was associated with a higher rate of new onset organ failure (OR: 2.47; 95% CI: 1.23-4.84). When the stomach or duodenum was affected, treatment was mostly conservative (n=54, 68%). Treatment was mostly surgical when the colon was affected (n=38, 59%). CONCLUSIONS: Perforation and fistula of the GI tract occurred in one out of six pat

Item does not contain fulltext, OBJECTIVE: To describe outcome after pancreatic surgery in the first 6 years of a mandatory nationwide audit. BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: During the first 6 years of a nationwide audit, in-hospital mortality and FTR af

Item does not contain fulltext, OBJECTIVE: To evaluate the performance of published fistula risk models by external validation, and to identify independent risk factors for postoperative pancreatic fistula (POPF). BACKGROUND: Multiple risk models have been developed to predict POPF after pancreatoduodenectomy. External validation in high-quality prospective cohorts is, however, lacking or only performed for individual models. METHODS: A post hoc analysis of data from the stepped-wedge cluster cluster-randomized Care After Pancreatic Resection According to an Algorithm for Early Detection and Minimally Invasive Management of Pancreatic Fistula versus Current Practice (PORSCH) trial was performed. Included were all patients undergoing pancreatoduodenectomy in the Netherlands (January 2018-November 2019). Risk models on POPF were identified by a systematic literature search. Model performance was evaluated by calculating the area under the receiver operating curves (AUC) and calibration plots. Multivariable logistic regression was performed to identify independent risk factors associated with clinically relevant POPF. RESULTS: Overall, 1358 patients undergoing pancreatoduodenectomy were included, of whom 341 patients (25%) developed clinically relevant POPF. Fourteen risk models for POPF were evaluated, with AUCs ranging from 0.62 to 0.70. The updated alternative fistula risk score had an AUC of 0.70 (95% confidence intervals [CI]: 0.69-0.72). The alternative fistula risk score demonstrated an AUC of 0.70 (95% CI: 0.689-0.71), whilst an AUC of 0.70 (95% CI: 0.699-0.71) was also found for the model by Petrova and colleagues. Soft pancreatic texture, pathology other than pancreatic ductal adenocarcinoma or chronic pancreatitis, small pancreatic duct diameter, higher body mass index, minimally invasive resection and male sex were identified as independent predictors of POPF. CONCLUSION: Published risk models predicting clinically relevant POPF after pancreatoduodenectomy have a moderate predictive accur

Contains fulltext : 300064.pdf (Publisher’s version ) (Open Access), BACKGROUND: We developed models for tumor segmentation to automate the assessment of total tumor volume (TTV) in patients with colorectal liver metastases (CRLM). METHODS: In this prospective cohort study, pre- and post-systemic treatment computed tomography (CT) scans of 259 patients with initially unresectable CRLM of the CAIRO5 trial (NCT02162563) were included. In total, 595 CT scans comprising 8,959 CRLM were divided into training (73%), validation (6.5%), and test sets (21%). Deep learning models were trained with ground truth segmentations of the liver and CRLM. TTV was calculated based on the CRLM segmentations. An external validation cohort was included, comprising 72 preoperative CT scans of patients with 112 resectable CRLM. Image segmentation evaluation metrics and intraclass correlation coefficient (ICC) were calculated. RESULTS: In the test set (122 CT scans), the autosegmentation models showed a global Dice similarity coefficient (DSC) of 0.96 (liver) and 0.86 (CRLM). The corresponding median per-case DSC was 0.96 (interquartile range [IQR] 0.95-0.96) and 0.80 (IQR 0.67-0.87). For tumor segmentation, the intersection-over-union, precision, and recall were 0.75, 0.89, and 0.84, respectively. An excellent agreement was observed between the reference and automatically computed TTV for the test set (ICC 0.98) and external validation cohort (ICC 0.98). In the external validation, the global DSC was 0.82 and the median per-case DSC was 0.60 (IQR 0.29-0.76) for tumor segmentation. CONCLUSIONS: Deep learning autosegmentation models were able to segment the liver and CRLM automatically and accurately in patients with initially unresectable CRLM, enabling automatic TTV assessment in such patients. RELEVANCE STATEMENT: Automatic segmentation enables the assessment of total tumor volume in patients with colorectal liver metastases, with a high potential of decreasing radiologist's workload and increasing accuracy and consistency. KEY POINTS: • Tumor response eval