In two RCTs, comparing neoadjuvant chemoradiotherapy (CRT) with upfront surgery in patients with resectable and borderline resectable pancreatic cancers, CRT was associated with better survival.... Show moreIn two RCTs, comparing neoadjuvant chemoradiotherapy (CRT) with upfront surgery in patients with resectable and borderline resectable pancreatic cancers, CRT was associated with better survival. There was no difference in treatment effect between patients with a baseline CA19-9 level higher or lower than 500 units/ml, meaning that neoadjuvant CRT should not be withheld because of a low CA19-9 concentration.Background Guidelines suggest that the serum carbohydrate antigen (CA19-9) level should be used when deciding on neoadjuvant treatment in patients with resectable and borderline resectable pancreatic ductal adenocarcinoma (hereafter referred to as pancreatic cancer). In patients with resectable pancreatic cancer, neoadjuvant therapy is advised when the CA19-9 level is 'markedly elevated'. This study investigated the impact of baseline CA19-9 concentration on the treatment effect of neoadjuvant chemoradiotherapy (CRT) in patients with resectable and borderline resectable pancreatic cancers. Methods In this post hoc analysis, data were obtained from two RCTs that compared neoadjuvant CRT with upfront surgery in patients with resectable and borderline resectable pancreatic cancers. The effect of neoadjuvant treatment on overall survival was compared between patients with a serum CA19-9 level above or below 500 units/ml using the interaction test. Results Of 296 patients, 179 were eligible for analysis, 90 in the neoadjuvant CRT group and 89 in the upfront surgery group. Neoadjuvant CRT was associated with superior overall survival (HR 0.67, 95 per cent c.i. 0.48 to 0.94; P = 0.019). Among 127 patients (70, 9 per cent) with a low CA19-9 level, median overall survival was 23.5 months with neoadjuvant CRT and 16.3 months with upfront surgery (HR 0.63, 0.42 to 0.93). For 52 patients (29 per cent) with a high CA19-9 level, median overall survival was 15.5 months with neoadjuvant CRT and 12.9 months with upfront surgery (HR 0.82, 0.45 to 1.49). The interaction test for CA19-9 level exceeding 500 units/ml on the treatment effect of neoadjuvant CRT was not significant (P = 0.501). Conclusion Baseline serum CA19-9 level defined as either high or low has prognostic value, but was not associated with the treatment effect of neoadjuvant CRT in patients with resectable and borderline resectable pancreatic cancers, in contrast with current guideline advice. Show less
Introduction: Lymph node ratio (LNR) is an important prognostic factor of survival in patients with pancreatic ductal adenocarcinoma (PDAC). This study aimed to validate three LNR-based nomograms... Show moreIntroduction: Lymph node ratio (LNR) is an important prognostic factor of survival in patients with pancreatic ductal adenocarcinoma (PDAC). This study aimed to validate three LNR-based nomograms using an international cohort. Materials and methods: Consecutive PDAC patients who underwent upfront pancreatoduodenectomy from six centers (Europe/USA) were collected (2000-2017). Patients with metastases, R2 resection, missing LNR data, and who died within 90 postoperative days were excluded. The updated Amsterdam nomogram, the nomogram by Pu et al., and the nomogram by Li et al. were selected. For the validation, calibration, discrimination capacity, and clinical utility were assessed. Results: After exclusion of 176 patients, 10113 patients were included. Median overall survival (OS) of the cohort was 23 months (95% CI: 21-25). For the three nomograms, Kaplan-Meier curves showed significant OS diminution with increasing scores (p < 0.01). All nomograms showed good calibration (non-significant Hosmer-Lemeshow tests). For the Amsterdam nomogram, area under the ROC curve (AUROC) for 3-year OS was 0.64 and 0.67 for 5-year OS. Sensitivity and specificity for 3-year OS prediction were 65% and 59%. Regarding the nomogram by Pu et al., AUROC for 3- and 5-year OS were 0.66 and 0.70. Sensitivity and specificity for 3-year OS prediction were 68% and 53%. For the Li nomogram, AUROC for 3- and 5-year OS were 0.67 and 0.71, while sensitivity and specificity for 3-year OS prediction were 63% and 60%. Conclusion: The three nomograms were validated using an international cohort. Those nomograms can be used in clinical practice to evaluate survival after pancreatoduodenectomy for PDAC. (c) 2022 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). Show less
Background: Venous resection of the superior mesenteric or portal vein is increasingly performed in pancreatic cancer surgery, whereas results of studies on short- and long-term outcomes are... Show moreBackground: Venous resection of the superior mesenteric or portal vein is increasingly performed in pancreatic cancer surgery, whereas results of studies on short- and long-term outcomes are contradictory. The aim of this study was to evaluate the impact of the type of venous resection in pancreatoduodenectomy for pancreatic cancer on postoperative morbidity and overall survival.Methods: This nationwide retrospective cohort study included all patients who underwent pancreatoduodenectomy for pancreatic cancer in 18 centres (2013-2017).Results: A total of 1311 patients were included, of whom 17 per cent underwent wedge resection and 10 per cent segmental resection. Patients with segmental resection had higher rates of major morbidity (39 versus 20 versus 23 per cent, respectively; P < 0.001) and portal or superior mesenteric vein thrombosis (18 versus 5 versus 1 per cent, respectively; P < 0.001) and worse overall survival (median 12 versus 16 versus 20months, respectively; P < 0.001), compared to patients with wedge resection and those without venous resection. Multivariable analysis showed patients with segmental resection, but not those who had wedge resection, had higher rates of major morbidity (odds ratio = 1.93, 95 per cent c.i. 1.20 to 3.11) and worse overall survival (hazard ratio = 1.40, 95 per cent c.i. 1.10 to 1.78), compared to patients without venous resection. Among patients who received neoadjuvant therapy, there was no difference in overall survival among patients with segmental and wedge resection and those without venous resection (median 32 versus 25 versus 33months, respectively; P = 0.470), although there was a difference in majormorbidity rates (52 versus 19 versus 21 per cent, respectively; P = 0.012).Conclusion: In pancreatic surgery, the short- and long-term outcomes are worse in patients with venous segmental resection, compared to patients with wedge resection and those without venous resection. Show less
Background Venous resection of the superior mesenteric or portal vein is increasingly performed in pancreatic cancer surgery, whereas results of studies on short- and long-term outcomes are... Show moreBackground Venous resection of the superior mesenteric or portal vein is increasingly performed in pancreatic cancer surgery, whereas results of studies on short- and long-term outcomes are contradictory. The aim of this study was to evaluate the impact of the type of venous resection in pancreatoduodenectomy for pancreatic cancer on postoperative morbidity and overall survival. Methods This nationwide retrospective cohort study included all patients who underwent pancreatoduodenectomy for pancreatic cancer in 18 centres (2013-2017). Results A total of 1311 patients were included, of whom 17 per cent underwent wedge resection and 10 per cent segmental resection. Patients with segmental resection had higher rates of major morbidity (39 versus 20 versus 23 per cent, respectively; P < 0.001) and portal or superior mesenteric vein thrombosis (18 versus 5 versus 1 per cent, respectively; P < 0.001) and worse overall survival (median 12 versus 16 versus 20 months, respectively; P < 0.001), compared to patients with wedge resection and those without venous resection. Multivariable analysis showed patients with segmental resection, but not those who had wedge resection, had higher rates of major morbidity (odds ratio = 1.93, 95 per cent c.i. 1.20 to 3.11) and worse overall survival (hazard ratio = 1.40, 95 per cent c.i. 1.10 to 1.78), compared to patients without venous resection. Among patients who received neoadjuvant therapy, there was no difference in overall survival among patients with segmental and wedge resection and those without venous resection (median 32 versus 25 versus 33 months, respectively; P = 0.470), although there was a difference in major morbidity rates (52 versus 19 versus 21 per cent, respectively; P = 0.012). Conclusion In pancreatic surgery, the short- and long-term outcomes are worse in patients with venous segmental resection, compared to patients with wedge resection and those without venous resection.Of 1311 patients who underwent pancreatoduodenectomy, 17 per cent underwent venous wedge resection and 10 per cent underwent venous segmental resection. Venous segmental, but not venous wedge, resection was associated with higher major morbidity rates (odds ratio = 1.93, 95 per cent c.i. 1.20 to 3.11) and worse overall survival (hazard ratio = 1.40, 95 per cent c.i. 1.10 to 1.78), compared to no venous resection. This nationwide study found worse short- and long-term outcomes in patients who had venous segmental resection. The results of this study urge the need for improving outcomes in patients who require venous segmental resection. Show less
Introduction: Whereas neoadjuvant chemo(radio)therapy is increasingly used in pancreatic cancer, it is currently not recommended for other periampullary (non-pancreatic) cancers. This has important... Show moreIntroduction: Whereas 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. Methods: Data 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). Results: In 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. Discussion: This 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. (c) 2021 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). Show less
Groen, J.V.; Manen, L. van; Roessel, S. van; Dam, J.L. van; Bonsing, B.A.; Doukas, M.; ... ; Mieog, J.S.D. 2021
Objectives The portal vein (PV)-superior mesenteric vein (SMV) margin is the most affected margin in pancreatic cancer. This study investigates the association between venous resection, tumor... Show moreObjectives The portal vein (PV)-superior mesenteric vein (SMV) margin is the most affected margin in pancreatic cancer. This study investigates the association between venous resection, tumor invasion in the resected PV-SMV, recurrence patterns, and overall survival (OS). Methods This multicenter cohort study included patients who underwent pancreatoduodenectomy for pancreatic cancer (2010-2017). In addition, a systematic literature search was performed. Results In total, 531 patients were included, of which 149 (28%) underwent venous resection of whom 53% had tumor invasion in the resected PV-SMV. Patients with venous resection had a significant higher rate of R1 margins (69% vs 37%) and had more often multiple R1 margins (43% vs 16%). Patient with venous resection had a significant shorter time to locoregional recurrence and a shorter OS (15 vs 19 months). At multivariable analyses, venous resection and tumor invasion in the resected PV-SMV were not predictive for time to recurrence and OS. The literature overview showed that pathological assessment of the resected PV-SMV is not adequately standardized. Conclusions Only half of patients with venous resection had pathology confirmed tumor invasion in the resected PV-SMV, and both are not independently associated with time to recurrence and OS. The pathological assessment of the resected PV-SMV needs to be standardized. Show less
Background: Lymph node ratio (LNR; positive/harvested lymph nodes) was identified as overall survival predictor in several cancers, including pancreatic adenocarcinoma. It remains unclear if LNR is... Show moreBackground: Lymph node ratio (LNR; positive/harvested lymph nodes) was identified as overall survival predictor in several cancers, including pancreatic adenocarcinoma. It remains unclear if LNR is predictive of overall survival in pancreatic adenocarcinoma patients staged pN2. This study assessed the prognostic overall survival role of LNR in pancreatic adenocarcinoma patients in relation with lymph node involvement.Methods: A retrospective international study in six different centers (Europe and United States) was performed. Pancreatic adenocarcinoma patients who underwent pancreatoduodenectomy from 2000 to 2017 were included. Patients with neoadjuvant treatment, metastases, R2 resections, or missing data regarding nodal status were excluded. Survival curves were calculated using Kaplan-Meier method and compared using log-rank test. Multivariable Cox regressions were performed to find independent overall survival predictors adjusted for potential confounders.Results: A total of 1,327 patients were included. Lymph node involvement (pN+) was found in 1,026 patients (77%), 561 pN1 (55%) and 465 pN2 (45%). Median LNR in pN+ patients was 0.214 (IQR: 0.105-0.364). On multivariable analysis, LNR was the strongest overall survival predictor in the entire cohort (HR 5.5, 95% CI: 3.1-9.9, P<0.001) and pN+ patients (HR 3.8, 95% CI: 2.2-6.6, P<0.001). Median overall survival was better in patients with LNR <0.225 compared to patients with LNR >= 0.225 in the entire cohort and pN+ patients. Similar results were found in pN2 patients (worse overall survival when LNR >= 0.225).Conclusions: LNR appeared as an important prognostic factor in patients undergoing surgery for pancreatic adenocarcinoma and permitted to stratify overall survival in pN2 patients. LNR should be routinely used in complement to TNM stage to better predict patient prognosis. Show less
Roessel, S. van; Strijker, M.; Steyerberg, E.W.; Groen, J.V.; Mieog, J.S.; Groot, V.P.; ... ; Besselink, M.G. 2020
Background: The objective of this study was to validate and update the Amsterdam prediction model including tumor grade, lymph node ratio, margin status and adjuvant therapy, for prediction of... Show moreBackground: The objective of this study was to validate and update the Amsterdam prediction model including tumor grade, lymph node ratio, margin status and adjuvant therapy, for prediction of overall survival (OS) after pancreatoduodenectomy for pancreatic cancer.Methods: We included consecutive patients who underwent pancreatoduodenectomy for pancreatic cancer between 2000 and 2017 at 11 tertiary centers in 8 countries (USA, UK, Germany, Italy, Sweden, the Netherlands, Korea, Australia). Model performance for prediction of OS was evaluated by calibration statistics and Uno's C-statistic for discrimination. Validation followed the TRIPOD statement.Results: Overall, 3081 patients (53% male, median age 66 years) were included with a median OS of 24 months, of whom 38% had N2 disease and 77% received adjuvant chemotherapy. Predictions of 3-year OS were fairly similar to observed OS with a calibration slope of 0.72. Statistical updating of the model resulted in an increase of the C-statistic from 0.63 to 0.65 (95% CI 0.64-0.65), ranging from 0.62 to 0.67 across different countries. The area under the curve for the prediction of 3 -year OS was 0.71 after updating. Median OS was 36, 25 and 15 months for the low, intermediate and high risk group, respectively (P < 0.001).Conclusions: This large international study validated and updated the Amsterdam model for survival prediction after pancreatoduodenectomy for pancreatic cancer. The model incorporates readily available variables with a fairly accurate model performance and robustness across different countries, while novel markers may be added in the future. The risk groups and web-based calculator www pancreascalculaior. corn may facilitate use in daily practice and future trials. (C) 2019 Elsevier Ltd, BASO The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved. Show less
Background Conditional survival is the survival probability after already surviving a predefined time period. This may be informative during follow-up, especially when adjusted for tumor... Show moreBackground Conditional survival is the survival probability after already surviving a predefined time period. This may be informative during follow-up, especially when adjusted for tumor characteristics. Such prediction models for patients with resected pancreatic cancer are lacking and therefore conditional survival was assessed and a nomogram predicting 5-year survival at a predefined period after resection of pancreatic cancer was developed. Methods This population-based study included patients with resected pancreatic ductal adenocarcinoma from the Netherlands Cancer Registry (2005-2016). Conditional survival was calculated as the median, and the probability of surviving up to 8 years in patients who already survived 0-5 years after resection was calculated using the Kaplan-Meier method. A prediction model was constructed. Results Overall, 3082 patients were included, with a median age of 67 years. Median overall survival was 18 months (95% confidence interval 17-18 months), with a 5-year survival of 15%. The 1-year conditional survival (i.e. probability of surviving the next year) increased from 55 to 74 to 86% at 1, 3, and 5 years after surgery, respectively, while the median overall survival increased from 15 to 40 to 64 months at 1, 3, and 5 years after surgery, respectively. The prediction model demonstrated that the probability of achieving 5-year survival at 1 year after surgery varied from 1 to 58% depending on patient and tumor characteristics. Conclusions This population-based study showed that 1-year conditional survival was 55% 1 year after resection and 74% 3 years after resection in patients with pancreatic cancer. The prediction model is available via to inform patients and caregivers. Show less
Roessel, S. van; Mackay, T.M.; Dieren, S. van; Schelling, G.P. van der; Nieuwenhutjs, V.B.; Bosscha, K.; ... ; Dutch Pancreatic Canc Grp 2020
Background: Textbook outcome (TO) is a multidimensional measure for quality assurance, reflecting the "ideal" surgical outcome. Methods: Post-hoc analysis of patients who underwent... Show moreBackground: Textbook outcome (TO) is a multidimensional measure for quality assurance, reflecting the "ideal" surgical outcome. Methods: Post-hoc analysis of patients who underwent pancreatoduodenectomy (PD) or distal pancreatectomy (DP) for all indications between 2014 and 2017, queried from the nationwide prospective Dutch Pancreatic Cancer Audit. An international survey was conducted among 24 experts from 10 countries to reach consensus on the requirements for TO in pancreatic surgery. Univariable and multivariable logistic regression was performed to identify TO predictors. Between-hospital variation in TO rates was compared using observed-versus-expected rates. Results: Based on the survey (92% response rate), TO was defined by the absence of postoperative pancreatic fistula, bile leak, postpancreatectomy hemorrhage (all ISGPS grade B/C), severe complications (Clavien-Dindo >= III), readmission, and in-hospital mortality. Overall, 3341 patients were included (2633 (79%) PD and 708 (21%) DP) of whom 60.3% achieved TO; 58.3% for PD and 67.4% for DP. On multivariable analysis, ASA class 3 predicted a worse TO rate after PD (ASA 3 OR 0.59 [0.44-0.80]), whereas a dilated pancreatic duct (>3 mm) and pancreatic ductal adenocarcinoma (PDAC) were associated with a better TO rate (OR 2.22 [2.05-3.57] and OR 1.36 [1.14-1.63], respectively). For DP, female sex and the absence of neoadjuvant therapy predicted better TO rates (OR 1.38 [1.01-1.90] and OR 2.53 [1.20-5.31], respectively). When comparing institutions, the observed-versus-expected rate for achieving TO varied from 0.71 to 1.46 per hospital after casemix-adjustment. Conclusions: TO is a novel quality measure in pancreatic surgery. TO varies considerably between pancreatic centers, demonstrating the potential benefit of quality assurance programs. Show less
