BackgroundSurgical resection followed by adjuvant mFOLFIRINOX (5-fluorouracil with leucovorin, irinotecan, and oxaliplatin) is currently the standard of care for patients with resectable pancreatic... Show moreBackgroundSurgical resection followed by adjuvant mFOLFIRINOX (5-fluorouracil with leucovorin, irinotecan, and oxaliplatin) is currently the standard of care for patients with resectable pancreatic cancer. The main concern regarding adjuvant chemotherapy is that only half of patients actually receive adjuvant treatment. Neoadjuvant chemotherapy, on the other hand, guarantees early systemic treatment and may increase chemotherapy use and thereby improve overall survival. Furthermore, it may prevent futile surgery in patients with rapidly progressive disease. However, some argue that neoadjuvant therapy delays surgery, which could lead to progression towards unresectable disease and thus offset the potential benefits. Comparison of perioperative (i.e., neoadjuvant and adjuvant) with (only) adjuvant administration of mFOLFIRINOX in a randomized controlled trial (RCT) is needed to determine the optimal approach.MethodsThis multicenter, phase 3, RCT will include 378 patients with resectable pancreatic ductal adenocarcinoma with a WHO performance status of 0 or 1. Patients are recruited from 20 Dutch centers and three centers in Norway and Sweden. Resectable pancreatic cancer is defined as no arterial contact and & LE; 90 degrees venous contact. Patients in the intervention arm are scheduled for 8 cycles of neoadjuvant mFOLFIRINOX followed by surgery and 4 cycles of adjuvant mFOLFIRINOX (2-week cycle of oxaliplatin 85 mg/m(2), leucovorin 400 mg/m(2), irinotecan 150 mg/m(2) at day 1, followed by 46 h continuous infusion of 5-fluorouracil 2400 g/m(2)). Patients in the comparator arm start with surgery followed by 12 cycles of adjuvant mFOLFIRINOX. The primary outcome is overall survival by intention-to-treat. Secondary outcomes include progression-free survival, resection rate, quality of life, adverse events, and surgical complications. To detect a hazard ratio of 0.70 with 80% power, 252 events are needed. The number of events is expected to be reached after the inclusion of 378 patients in 36 months, with analysis planned 18 months after the last patient has been randomized.DiscussionThe multicenter PREOPANC-3 trial compares perioperative mFOLFIRINOX with adjuvant mFOLFIRINOX in patients with resectable pancreatic cancer. Show less
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... Show moreObjective: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. Show less
Background: Abdominal symptoms after cholecystectomy may be caused by gallstones in a remnant gallbladder or a long cystic duct stump. Resection of a remnant gallbladder or cystic duct stump is... Show moreBackground: Abdominal symptoms after cholecystectomy may be caused by gallstones in a remnant gallbladder or a long cystic duct stump. Resection of a remnant gallbladder or cystic duct stump is associated with an increased risk of conversion and bile duct or vascular injuries. We prospectively investigated the additional value of robotic assistance and fluorescent bile duct illumination in redo biliary surgery.Methods: In this prospective two-centre observational cohort study, 28 patients were included with an indication for redo biliary surgery because of remnant stones in a remnant gallbladder or long cystic duct stump. Surgery was performed with the da Vinci X & REG; and Xi & REG; robotic system. The biliary tract was visualised in the fluorescence Firefly & REG; mode shortly after intravenous injection of indocyanine green.Results: There were no conversions or perioperative complications, especially no vascular or bile duct injuries. Fluorescence-based illumination of the extrahepatic bile ducts was successful in all cases. Symptoms were resolved in 27 of 28 patients. Ten patients were treated in day care and 13 patients were discharged the day after surgery.Conclusion: Robot-assisted fluorescence-guided surgery for remnant gallbladder or cystic duct stump resection is safe, effective and can be done in day-care setting. Show less
Introduction In 2017, the Southampton guideline stated that minimally invasive liver resections (MILR) should considered standard practice for minor liver resections. This study aimed to assess... Show moreIntroduction In 2017, the Southampton guideline stated that minimally invasive liver resections (MILR) should considered standard practice for minor liver resections. This study aimed to assess recent implementation rates of minor MILR, factors associated with performing MILR, hospital variation, and outcomes in patients with colorectal liver metastases (CRLM).Methods This population-based study included all patients who underwent minor liver resection for CRLM in the Netherlands between 2014 and 2021. Factors associated with MILR and nationwide hospital variation were assessed using multilevel multivariable logistic regression. Propensity-score matching (PSM) was applied to compare outcomes between minor MILR and minor open liver resections. Overall survival (OS) was assessed with Kaplan-Meier analysis on patients operated until 2018.Results Of 4,488 patients included, 1,695 (37.8%) underwent MILR. PSM resulted in 1,338 patients in each group. Implementation of MILR increased to 51.2% in 2021. Factors associated with not performing MILR included treatment with preoperative chemotherapy (aOR 0.61 CI:0.50-0.75, p < 0.001), treatment in a tertiary referral hospital (aOR 0.57 CI:0.50-0.67, p < 0.001), and larger diameter and number of CRLM. Significant hospital variation was observed in use of MILR (7.5% to 93.0%). After case-mix correction, six hospitals performed fewer, and six hospitals performed more MILRs than expected. In the PSM cohort, MILR was associated with a decrease in blood loss (aOR 0.99 CI:0.99-0.99, p < 0.01), cardiac complications (aOR 0.29, CI:0.10-0.70, p = 0.009), IC admissions (aOR 0.66, CI:0.50-0.89, p = 0.005), and shorter hospital stay (aOR CI:0.94-0.99, p < 0.01). Five-year OS rates for MILR and OLR were 53.7% versus 48.6%, p = 0.21.Conclusion Although uptake of MILR is increasing in the Netherlands, significant hospital variation remains. MILR benefits short-term outcomes, while overall survival is comparable to open liver surgery.[GRAPHICS]. Show less
Background: The necessity of the staging laparoscopy in patients with pancreatic cancer is still debated. The objective of this study was to assess the yield of staging laparoscopy for detecting... Show moreBackground: The necessity of the staging laparoscopy in patients with pancreatic cancer is still debated. The objective of this study was to assess the yield of staging laparoscopy for detecting occult metastases in patients with resectable or borderline resectable pancreatic cancer.Method: This was a post-hoc analysis of the randomized controlled PREOPANC trial in which patients with resectable or borderline resectable pancreatic cancer were randomized between preoperative chemoradiotherapy or immediate surgery. Patients assigned to preoperative treatment underwent a staging laparoscopy prior to preoperative treatment according to protocol, to avoid unnecessary che-moradiotherapy in patients with occult metastatic disease.Results: Of the 246 included patients, 7 did not undergo surgery. A staging laparoscopy was performed in 133 patients (55.6%) and explorative laparotomy in 106 patients (4 4.4%). At staging laparoscopy, occult metastases were detected in 13 patients (9.8%); 12 liver metastases and 1 peritoneal metastasis. At direct explorative laparotomy, occult metastases were found in 9 patients (8.5%); 6 with liver metastases, 1 with peritoneal metastases, and 2 with metastases at multiple sites. One patient had peritoneal metastases at exploration after a negative staging laparoscopy. Patients with occult metastases were more likely to receive palliative chemotherapy if found with staging laparoscopy compared to laparotomy (76.9% vs. 30.0%, p 1/4 0.040).Conclusions: Staging laparoscopy detected occult metastases in about 10% of patients with resectable or borderline resectable pancreatic cancer. These patients were more likely to receive palliative systemic chemotherapy compared to patients in whom occult metastases were detected with laparotomy. A staging laparoscopy is recommended before planned resection.(c) 2022 Published by Elsevier Ltd. Show less
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... Show moreBackground 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 treatment of complications and use of neoadjuvant treatment may improve oncological outcomes.This nationwide observational cohort study included 1052 patients and showed that major complications, including organ failure, have a negative impact on disease-free interval and overall survival after resection of pancreatic cancer. This effect was largely mediated by the use of adjuvant chemotherapy. Show less
Introduction: Textbook outcome (TO) is a composite outcome measure covering the surgical care process in a single outcome measure. TO has an advantage over single outcome parameters with low event... Show moreIntroduction: Textbook outcome (TO) is a composite outcome measure covering the surgical care process in a single outcome measure. TO has an advantage over single outcome parameters with low event rates, which have less discriminating impact to detect differences between hospitals. This study aimed to assess factors associated with TO, and evaluate hospital and network variation after case-mix correction in TO rates for liver surgery. Methods: This was a population-based retrospective study of all patients who underwent liver resection for malignancy in the Netherlands in 2019 and 2020. TO was defined as absence of severe postoperative complications, mortality, prolonged length of hospital stay, and readmission, and obtaining adequate resection margins. Multivariable logistic regression was used for case-mix adjustment. Results: 2376 patients were included. TO was accomplished in 1380 (80%) patients with colorectal liver metastases, in 192 (76%) patients with other liver metastases, in 183 (74%) patients with hepatocellular carcinoma and 86 (51%) patients with biliary cancers. Factors associated with lower TO rates for CRLM included ASA score >= 3 (aOR 0.70, CI 0.51-0.95 p = 0.02), extrahepatic disease (aOR 0.64, CI 0.44-0.95, p = 0.02), tumour size >55 mm on preoperative imaging (aOR 0.56, CI 0.34-0.94, p = 0.02), Charlson Comorbidity Index >= 2 (aOR 0.73, CI 0.54-0.98, p = 0.04), and major liver resection (aOR 0.50, CI 0.36-0.69, p < 0.001). After case-mix correction, no significant hospital or oncological network variation was observed. Conclusion: TO differs between indications for liver resection and can be used to assess between hospital and network differences. (c) 2022 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). Show less
Hepatocellular adenomas (HCAs) are benign liver tumors associated with bleeding or malignant transformation. Data on the indication for surgery are scarce. We analyzed indications and outcome of... Show moreHepatocellular adenomas (HCAs) are benign liver tumors associated with bleeding or malignant transformation. Data on the indication for surgery are scarce. We analyzed indications and outcome of patients operated for HCAs < 50 mm compared to HCAs >= 50 mm. Changes in final postoperative diagnosis were assessed. We performed a retrospective study that included patients who underwent resection for (suspected) HCAs in the Netherlands from 2014 to 2019. Indication for resection was analyzed and stratified for small (<50 mm) and large (>= 50 mm) tumors. Logistic regression analysis was performed on factors influencing change in tumor diagnosis. Out of 222 patients who underwent surgery, 44 (20%) patients had a tumor <50 mm. Median age was 46 (interquartile range [IQR], 33-56) years in patients with small tumors and 37 (IQR, 31-46) years in patients with large tumors (p = 0.016). Patients with small tumors were more frequently men (21% vs. 5%, p = 0.002). Main indications for resection in patients with small tumors were suspicion of (pre)malignancy (55%), (previous) bleeding (14%), and male sex (11%). Patients with large tumors received operations because of tumor size >50 mm (52%), suspicion of (pre)malignancy (28%), and (previous) bleeding (5.1%). No difference was observed in HCA-subtype distribution between small and large tumors. Ninety-six (43%) patients had a postoperative change in diagnosis. Independent risk factors for change in diagnosis were tumor size <50 mm (adjusted odds ratio [aOR], 3.4; p < 0.01), male sex (aOR, 3.7; p = 0.03), and lack of hepatobiliary contrast-enhanced magnetic resonance imaging (CE-MRI) (aOR, 1.8; p = 0.04). Resection for small (suspected) HCAs was mainly indicated by suspicion of (pre)malignancy, whereas for large (suspected) HCAs, tumor size was the most prevalent indication. Male sex, tumor size <50 mm, and lack of hepatobiliary CE-MRI were independent risk factors for postoperative change in tumor diagnosis. Show less
Stoop, T.F.; Mackay, T.M.; Brada, L.J.H.; Harst, E. van der; Daams, F.; Land, F.R. van 't; ... ; Dutch Pancreatic Canc Grp 2022
Introduction: Arterial resections in pancreatic surgery may be planned to obtain a radical oncological resection, or unplanned after iatrogenic injury during dissection. Most data on planned... Show moreIntroduction: Arterial resections in pancreatic surgery may be planned to obtain a radical oncological resection, or unplanned after iatrogenic injury during dissection. Most data on planned arterial resection come from single, very-high-volume centres and suggest that these resections might be feasible and even beneficial after preoperative chemotherapy in highly selected patients with pancreatic cancer1–3. However, real-world data on such planned and unplanned arterial resection at a nationwide level are scarce4. Furthermore, distinctions between planned and unplanned arterial resection are seldomly reported, even though this might have clinical implications. The present study evaluated the incidence and surgical outcome of all planned and unplanned arterial resections for pancreatic and periampullary cancer in The Netherlands. Show less
Background: The optimal treatment sequence for patients with synchronous colorectal liver metastases (CRLM) remains uncertain. This study aimed to assess factors associated with the use of... Show moreBackground: The optimal treatment sequence for patients with synchronous colorectal liver metastases (CRLM) remains uncertain. This study aimed to assess factors associated with the use of simultaneous resections and impact on hospital variation. Method: This population-based study included all patients who underwent liver surgery for synchronous colorectal liver metastases between 2014 and 2019 in the Netherlands. Factors associated with simultaneous resection were identified. Short-term surgical outcomes of simultaneous resections and factors associated with 30-day major morbidity were evaluated. Results: Of 2146 patients included, 589 (27%) underwent simultaneous resection in 28 hospitals. Simultaneous resection was associated with age, sex, BMI, number, size and bilobar distribution of CRLM, and administration of preoperative chemotherapy. More minimally invasive and minor resections were performed in the simultaneous group. Hospital variation was present (range 2.4%-83.3%) with several hospitals performing simultaneous procedures more and less frequently than expected. Simultaneous resection resulted in 13% 30-day major morbidity, and 1% mortality. ASA classification >3 was independently associated with higher 30-day major morbidity after simultaneous resection (aOR 1.97, CI 1.10-3.42, p = 0.018). Conclusion: Distinctive patient and tumour characteristics influence the choice for simultaneous resection. Remarkable hospital variation is present in the Netherlands. Show less
Background: Failure to rescue (FTR) is defined as postoperative complications leading to mortality. This nationwide study aimed to assess factors associated with FTR and hospital variation in FTR... Show moreBackground: Failure to rescue (FTR) is defined as postoperative complications leading to mortality. This nationwide study aimed to assess factors associated with FTR and hospital variation in FTR after liver surgery.Methods: All patients who underwent liver resection between 2014 and 2017 in the Netherlands were included. FTR was defined as in-hospital or 30-day mortality after complications Dindo grade >= 3a. Variables associated with FTR and nationwide hospital variation were assessed using multivariable lo-gistic regression.Results: Of 4961 patients included, 3707 (74.4%) underwent liver resection for colorectal liver me-tastases, 379 (7.6%) for other metastases, 526 (10.6%) for hepatocellular carcinoma and 349 (7.0%) for biliary cancer. Thirty-day major morbidity was 11.5%. Overall mortality was 2.3%. FTR was 19.1%. Age 65-80 (aOR: 2.86, CI:1.01-12.0, p = 0.049), ASA 3+ (aOR:2.59, CI: 1.66-4.02, p < 0.001), liver cirrhosis (aOR:4.15, CI:1.81-9.22, p < 0.001), biliary cancer (aOR:3.47, CI: 1.73-6.96, p < 0.001), and major resection (aOR:6.46, CI: 3.91-10.9, p < 0.001) were associated with FTR. Postoperative liver failure (aOR: 26.9, CI: 14.6-51.2, p < 0.001), cardiac (aOR: 2.62, CI: 1.27-5.29, p = 0.008) and thromboembolic complications (aOR: 2.49, CI: 1.16-5.22, p = 0.017) were associated with FTR. After case-mix correction, no hospital variation in FTR was observed.Conclusion: FTR is influenced by patient demographics, disease and procedural burden. Prevention of postoperative liver failure, cardiac and thromboembolic complications could decrease FTR. Show less
Background: Data regarding long-term quality of life and exocrine and endocrine insufficiency after pancreatic surgery for premalignant and benign (non-pancreatitis) disease are lacking. Methods:... Show moreBackground: Data regarding long-term quality of life and exocrine and endocrine insufficiency after pancreatic surgery for premalignant and benign (non-pancreatitis) disease are lacking. Methods: This cross-sectional study included patients >3 years after pancreatoduodenectomy or left pancreatectomy in six Dutch centers (2006-2016). Outcomes were measured with the EQ-5D-5L, the EORTC QLQ-C30, an exocrine and endocrine pancreatic insufficiency questionnaire, and PAID20. Results: Questionnaires were completed by 153/183 patients (response rate 84%, median follow-up 6.3 years). Surgery related complaints were reported by 72/153 patients (47%) and 13 patients (8.4%) would not undergo this procedure again. The VAS (EQ-5D-5L) was 76 +/- 17 versus 82 +/- 0.4 in the general population (p < 0.001). The mean global health status (QLQ-C30) was 78 +/- 17 versus 78 +/- 17, p = 1.000. Fatigue, insomnia, and diarrhea were clinically relevantly worse in patients. Exocrine pancreatic insufficiency was reported by 62 patients (41%) with relieve of symptoms by enzyme supplementation in 48%. New-onset diabetes mellitus was present in 22 patients (14%). The median PAID20 score was 6.9/20 (IQR 2.5-17.8). Conclusion: Although generic quality of life after pancreatic resection for pre-malignant and benign disease was similar to the general population and diabetes-related distress was low, almost half suffered from a range of symptoms highlighting the need for long-term counseling. Show less
Elfrink, A.K.E.; Nieuwenhuizen, S.; Tol, M.P. van den; Burgmans, M.C.; Prevoo, W.; Coolsen, M.M.E.; ... ; Dutch Hepato Bili 2021
Background: Combining resection and thermal ablation can improve short-term postoperative outcomes in patients with colorectal liver metastases (CRLM). This study assessed nationwide hospital... Show moreBackground: Combining resection and thermal ablation can improve short-term postoperative outcomes in patients with colorectal liver metastases (CRLM). This study assessed nationwide hospital variation and short-term postoperative outcomes after combined resection and ablation.Methods: In this population-based study, all CRLM patients who underwent resection in the Netherlands between 2014 and 2018 were included. After propensity score matching for age, ASA-score, Charlson-score, diameter of largest CRLM, number of CRLM and earlier resection, postoperative outcomes were compared. Postoperative complicated course (PCC) was defined as discharge after 14 days or a major complication or death within 30 days of surgery.Results: Of 4639 included patients, 3697 (80%) underwent resection and 942 (20%) resection and ablation. Unadjusted percentage of patients who underwent resection and ablation per hospital ranged between 4 and 44%. Hospital variation persisted after case-mix correction. After matching, 734 patients remained in each group. Hospital stay (median 6 vs. 7 days, p = 0.011), PCC (11% vs. 14.7%, p = 0.043) and 30-day mortality (0.7% vs. 2.3%, p = 0.018) were lower in the resection and ablation group. Differences faded in multivariable logistic regression due to inclusion of major hepatectomy.Conclusion: Significant hospital variation was observed in the Netherlands. Short-term postoperative outcomes were better after combined resection and ablation, attributed to avoiding complications associated with major hepatectomy. Show less
Background Neoadjuvant therapy has several potential advantages over upfront surgery in patients with localized pancreatic cancer; more patients receive systemic treatment, fewer patients undergo... Show moreBackground Neoadjuvant therapy has several potential advantages over upfront surgery in patients with localized pancreatic cancer; more patients receive systemic treatment, fewer patients undergo futile surgery, and R0 resection rates are higher, thereby possibly improving overall survival (OS). Two recent randomized trials have suggested benefit of neoadjuvant chemoradiotherapy over upfront surgery, both including single-agent chemotherapy regimens. Potentially, the multi-agent FOLFIRINOX regimen (5-fluorouracil with leucovorin, irinotecan, and oxaliplatin) may further improve outcomes in the neoadjuvant setting for localized pancreatic cancer, but randomized studies are needed. The PREOPANC-2 trial investigates whether neoadjuvant FOLFIRINOX improves OS compared with neoadjuvant gemcitabine-based chemoradiotherapy and adjuvant gemcitabine in resectable and borderline resectable pancreatic cancer patients.MethodsThis nationwide multicenter phase III randomized controlled trial includes patients with pathologically confirmed resectable and borderline resectable pancreatic cancer with a WHO performance score of 0 or 1. Resectable pancreatic cancer is defined as no arterial and <= 90 degrees venous involvement; borderline resectable pancreatic cancer is defined as <= 90 degrees arterial and <= 270 degrees venous involvement without occlusion. Patients receive 8cycles of neoadjuvant FOLFIRINOX chemotherapy followed by surgery without adjuvant treatment (arm A), or 3cycles of neoadjuvant gemcitabine with hypofractionated radiotherapy (36Gy in 15 fractions) during the second cycle, followed by surgery and 4cycles of adjuvant gemcitabine (arm B). The primary endpoint is OS by intention-to-treat. Secondary endpoints include progression-free survival, quality of life, resection rate, and R0 resection rate. To detect a hazard ratio of 0.70 with 80% power, 252 events are needed. The number of events is expected to be reached after inclusion of 368 eligible patients assuming an accrual period of 3years and 1.5years follow-up.DiscussionThe PREOPANC-2 trial directly compares two neoadjuvant regimens for patients with resectable and borderline resectable pancreatic cancer. Our study will provide evidence on the neoadjuvant treatment of choice for patients with resectable and borderline resectable pancreatic cancer.Trial registrationPrimary registry and trial identifying number: EudraCT: 2017-002036-17.Date of registration: March 6, 2018.Secondary identifying numbers: The Netherlands National Trial Register - NL7094, NL61961.078.17, MEC-2018-004. Show less
Background Evidence for an association between hospital volume and outcomes for liver surgery is abundant. The current Dutch guideline requires a minimum volume of 20 annual procedures per centre.... Show moreBackground Evidence for an association between hospital volume and outcomes for liver surgery is abundant. The current Dutch guideline requires a minimum volume of 20 annual procedures per centre. The aim of this study was to investigate the association between hospital volume and postoperative outcomes using data from the nationwide Dutch Hepato Biliary Audit. Methods This was a nationwide study in the Netherlands. All liver resections reported in the Dutch Hepato Biliary Audit between 2014 and 2017 were included. Annual centre volume was calculated and classified in categories of 20 procedures per year. Main outcomes were major morbidity (Clavien-Dindo grade IIIA or higher) and 30-day or in-hospital mortality. Results A total of 5590 liver resections were done across 34 centres with a median annual centre volume of 35 (i.q.r. 20-69) procedures. Overall major morbidity and mortality rates were 11 center dot 2 and 2 center dot 0 per cent respectively. The mortality rate was 1 center dot 9 per cent after resection for colorectal liver metastases (CRLMs), 1 center dot 2 per cent for non-CRLMs, 0 center dot 4 per cent for benign tumours, 4 center dot 9 per cent for hepatocellular carcinoma and 10 center dot 3 per cent for biliary tumours. Higher-volume centres performed more major liver resections, and more resections for hepatocellular carcinoma and biliary cancer. There was no association between hospital volume and either major morbidity or mortality in multivariable analysis, after adjustment for known risk factors for adverse events. Conclusion Hospital volume and postoperative outcomes were not associated. Show less
Elfrink, A.K.E.; Pool, M.; Werf, L.R. van der; Marra, E.; Burgmans, M.C.; Meijerink, M.R.; ... ; Dutch Hepatobiliary Audit Grp 2020
Background In patients with colorectal liver metastases (CRLM) preoperative imaging may include contrast-enhanced (ce) MRI and [F-18]fluorodeoxyglucose (F-18-FDG) PET-CT. This study assessed trends... Show moreBackground In patients with colorectal liver metastases (CRLM) preoperative imaging may include contrast-enhanced (ce) MRI and [F-18]fluorodeoxyglucose (F-18-FDG) PET-CT. This study assessed trends and variation between hospitals and oncological networks in the use of preoperative imaging in the Netherlands.Methods Data for all patients who underwent liver resection for CRLM in the Netherlands between 2014 and 2018 were retrieved from a nationwide auditing database. Multivariable logistic regression analysis was used to assess use of ceMRI, F-18-FDG PET-CT and combined ceMRI and F-18-FDG PET-CT, and trends in preoperative imaging and hospital and oncological network variation.Results A total of 4510 patients were included, of whom 1562 had ceMRI, 872 had F-18-FDG PET-CT, and 1293 had combined ceMRI and F-18-FDG PET-CT. Use of ceMRI increased over time (from 9.6 to 26.2 per cent; P < 0.001), use of F-18-FDG PET-CT decreased (from 28.6 to 6.0 per cent; P < 0.001), and use of both ceMRI and F-18-FDG PET-CT 16.9 per cent) remained stable. Unadjusted variation in the use of ceMRI, F-18-FDG PET-CT, and combined ceMRI and F-18-FDG PET-CT ranged from 5.6 to 100 per cent between hospitals. After case-mix correction, hospital and oncological network variation was found for all imaging modalities.Discussion Significant variation exists concerning the use of preoperative imaging for CRLM between hospitals and oncological networks in the Netherlands. The use of MRI is increasing, whereas that of F-18-FDG PET-CT is decreasing. Show less
BackgroundPancreatic cancer has a very poor prognosis. Best practices for the use of chemotherapy, enzyme replacement therapy, and biliary drainage have been identified but their implementation in... Show moreBackgroundPancreatic cancer has a very poor prognosis. Best practices for the use of chemotherapy, enzyme replacement therapy, and biliary drainage have been identified but their implementation in daily clinical practice is often suboptimal. We hypothesized that a nationwide program to enhance implementation of these best practices in pancreatic cancer care would improve survival and quality of life.Methods/designPACAP-1 is a nationwide multicenter stepped-wedge cluster randomized controlled superiority trial. In a per-center stepwise and randomized manner, best practices in pancreatic cancer care regarding the use of (neo)adjuvant and palliative chemotherapy, pancreatic enzyme replacement therapy, and metal biliary stents are implemented in all 17 Dutch pancreatic centers and their regional referral networks during a 6-week initiation period. Per pancreatic center, one multidisciplinary team functions as reference for the other centers in the network. Key best practices were identified from the literature, 3 years of data from existing nationwide registries within the Dutch Pancreatic Cancer Project (PACAP), and national expert meetings. The best practices follow the Dutch guideline on pancreatic cancer and the current state of the literature, and can be executed within daily clinical practice. The implementation process includes monitoring, return visits, and provider feedback in combination with education and reminders. Patient outcomes and compliance are monitored within the PACAP registries. Primary outcome is 1-year overall survival (for all disease stages). Secondary outcomes include quality of life, 3- and 5-year overall survival, and guideline compliance. An improvement of 10% in 1-year overall survival is considered clinically relevant. A 25-month study duration was chosen, which provides 80% statistical power for a mortality reduction of 10.0% in the 17 pancreatic cancer centers, with a required sample size of 2142 patients, corresponding to a 6.6% mortality reduction and 4769 patients nationwide.DiscussionThe PACAP-1 trial is designed to evaluate whether a nationwide program for enhanced implementation of best practices in pancreatic cancer care can improve 1-year overall survival and quality of life.Trial registrationClinicalTrials.gov, NCT03513705. Trial opened for accrual on 22th May 2018. Show less
Background: The relation between type of postoperative complication and not receiving chemotherapy after resection of pancreatic ductal adenocarcinoma (PDAC) is unclear. The aim was to investigate... Show moreBackground: The relation between type of postoperative complication and not receiving chemotherapy after resection of pancreatic ductal adenocarcinoma (PDAC) is unclear. The aim was to investigate which patient factors and postoperative complications were associated with not receiving adjuvant chemotherapy.Methods: Patients who underwent resection (2014-2017) for PDAC were identified from the nationwide mandatory Dutch Pancreatic Cancer Audit. The association between patient-, tumor-, center-, treatment characteristics, and the risk of not receiving adjuvant chemotherapy was analyzed with multivariable logistic regression.Results: Overall, of 1306 patients, 24% (n = 312) developed postoperative Clavien Dindo >3 complications. In-hospital mortality was 3.5% (n = 46). Some 433 patients (33%) did not receive adjuvant chemotherapy. Independent predictors (all p < 0.050) for not receiving adjuvant chemotherapy were older age (odds ratio (OR) 0.96), higher ECOG performance status (OR 0.57), postoperative complications (OR 0.32), especially grade B/C pancreatic fistula (OR 0.51) and post-pancreatectomy hemorrhage (OR 0.36), poor tumor differentiation grade (OR 0.62), and annual center volume of <40 pancreatoduodenectomies (OR 0.51).Conclusions: This study demonstrated that a third of patients do not receive chemotherapy after resection of PDAC. Next to higher age, worse performance status and lower annual surgical volume, this is mostly related to surgical complications, especially postoperative pancreatic fistula and postpancreatectomy hemorrhage. 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
