Feasibility, safety and preliminary efficacy of preoperative stereotactic radiotherapy on the future pancreatic neck transection margin to reduce the risk of pancreatic fistula after high-risk pancreatoduodenectomy (FIBROPANC): protocol for a multicentre, single-arm trial.

Introduction: Postoperative pancreatic fistula (POPF) occurs in 25% of patients undergoing a high-risk pancreatoduodenectomy (PD) and is a driving cause of major morbidity, mortality, prolonged hospital stay and increased costs after PD. There is a need for perioperative methods to decrease these risks. In recent studies, preoperative chemoradiotherapy in patients with pancreatic ductal adenocarcinoma (PDAC) reduced the rate of POPF seemingly due to radiation-induced pancreatic fibrosis.

Poor Prognostic Factors in Long-Term Survivors of Resected Pancreatic Ductal Adenocarcinoma: An International, Multicenter Cohort Study.

Objective: To measure the rate of LTS in resected PDAC and determine the association between predictors of OS and LTS.

Summary Background Data: Long-term survival (>5 y, LTS) remains rare in pancreatic ductal adenocarcinoma (PDAC). Multiple predictors of overall survival (OS) are known but their association with LTS remains unclear.

Perineural Invasion is an Important Prognostic Factor in Patients With Radically Resected (R0) and Node-negative (pN0) Pancreatic Cancer.

Objective: To investigate the association between perineural invasion (PNI) and overall survival (OS) in a nationwide cohort of patients with resected pancreatic ductal adenocarcinoma (PDAC), stratified for margin negative (R0) or positive (R1) resection and absence or presence of lymph node metastasis (pN0 or pN1-N2, respectively).

Background: Patients with R0 and pN0 resected PDAC have a relatively favorable prognosis. As PNI is associated with worse OS, this might be a useful factor to provide further prognostic information for patients counselling.

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

Occult metastases are detected in 10-15% of patients during exploratory laparotomy for pancreatic cancer. This study developed and externally validated a model to predict occult metastases in patients with potentially resectable pancreatic cancer. Model development was performed within the Dutch Pancreatic Cancer Audit, including all patients operated for pancreatic cancer (January 2013-December 2017).

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

Background: Postoperative pancreatic fistula remains the leading cause of significant morbidity after pancreatoduodenectomy for pancreatic ductal adenocarcinoma. Preoperative chemoradiotherapy has been described to reduce the risk of postoperative pancreatic fistula, but randomized trials on neoadjuvant treatment in pancreatic ductal adenocarcinoma focus increasingly on preoperative chemotherapy rather than preoperative chemoradiotherapy. This study aimed to investigate the impact of preoperative chemotherapy and preoperative chemoradiotherapy on postoperative pancreatic fistula and other pancreatic-specific surgery related complications on a nationwide level.

The Value of Biological and Conditional Factors for Staging of Patients with Resectable Pancreatic Cancer Undergoing Upfront Resection: A Nationwide Analysis.

Background: Novel definitions suggest that resectability status for pancreatic ductal adenocarcinoma (PDAC) should be assessed beyond anatomical criteria, considering both biological and conditional factors. This has, however, yet to be validated on a nationwide scale. This study evaluated the prognostic value of biological and conditional factors for staging of patients with resectable PDAC.

Fractures and other chest wall abnormalities after thoracotomy for esophageal cancer: A retrospective cohort study.

Background: Chest pain following a thoracotomy for esophageal cancer is frequently reported but poorly understood. This study aimed to (1) determine the prevalence of thoracotomy-related thoracic fractures on postoperative imaging and (2) compare complications, long-term pain, and quality of life in patients with versus without these fractures.

Methods: This retrospective cohort study enrolled patients with esophageal cancer who underwent a thoracotomy between 2010 and 2020 with pre- and postoperative CTs (<1 and/or >6 months).

Nationwide Use and Outcome of Surgery for Locally Advanced Pancreatic Cancer Following Induction Chemotherapy.

Background: Several international high-volume centers have reported good outcomes after resection of locally advanced pancreatic cancer (LAPC) following chemo(radio)therapy, but it is unclear how this translates to nationwide clinical practice and outcome. This study aims to assess the nationwide use and outcome of resection of LAPC following induction chemo(radio)therapy.

Patients And Methods: A multicenter retrospective study including all patients who underwent resection for LAPC following chemo(radio)therapy in all 16 Dutch pancreatic surgery centers (2014-2020), registered in the mandatory Dutch Pancreatic Cancer Audit.

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

Objective: To assess nationwide surgical outcome after pancreatoduodenectomy (PD) in patients at very high risk for postoperative pancreatic fistula (POPF), categorized as ISGPS-D.

Summary Background Data: Morbidity and mortality after ISGPS-D PD is perceived so high that a recent randomized trial advocated prophylactic total pancreatectomy (TP) as alternative aiming to lower this risk. However, current outcomes of ISGPS-D PD remain unknown as large nationwide series are lacking.

Practice variation in venous resection during pancreatoduodenectomy for pancreatic cancer: A nationwide cohort study.

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.

Predicting Long-term Disease-free Survival After Resection of Pancreatic Ductal Adenocarcinoma: A Nationwide Cohort Study.

Objective: To develop a prediction model for long-term (≥5 years) disease-free survival (DFS) after the resection of pancreatic ductal adenocarcinoma (PDAC).

Background: Despite high recurrence rates, ~10% of patients have long-term DFS after PDAC resection. A model to predict long-term DFS may aid individualized prognostication and shared decision-making.

Predictive value of baseline serum carbohydrate antigen 19-9 level on treatment effect of neoadjuvant chemoradiotherapy in patients with resectable and borderline resectable pancreatic cancer in two randomized trials.

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.

Nationwide use and Outcome of Minimally Invasive Distal Pancreatectomy in IDEAL Stage IV following a Training Program and Randomized Trial.

Objective: To assess the nationwide long-term uptake and outcomes of minimally invasive distal pancreatectomy (MIDP) after a nationwide training program and randomized trial.

Background: Two randomized trials demonstrated the superiority of MIDP over open distal pancreatectomy (ODP) in terms of functional recovery and hospital stay. Data on implementation of MIDP on a nationwide level are lacking.

Impact of complications after resection of pancreatic cancer on disease recurrence and survival, and mediation effect of adjuvant chemotherapy: nationwide, observational cohort study.

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).

Feasibility, safety, and efficacy of stereotactic body radiotherapy combined with intradermal heat-killed mycobacterium obuense (IMM-101) vaccination for non-progressive locally advanced pancreatic cancer, after induction chemotherapy with (modified)FOLFIRINOX - The LAPC-2 trial.

Background And Purpose: In this phase I/II trial, non-progressive locally advanced pancreatic cancer (LAPC) patients after (modified)FOLFIRINOX therapy were treated with stereotactic body radiotherapy (SBRT) combined with heat-killed mycobacterium (IMM-101) vaccinations. We aimed to assess safety, feasibility, and efficacy of this treatment approach.

Materials And Methods: On five consecutive days, patients received a total of 40 Gray (Gy) of SBRT with a dose of 8 Gy per fraction.

Risk Models for Developing Pancreatic Fistula After Pancreatoduodenectomy: Validation in a Nationwide Prospective Cohort.

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.

Targeted next-generation sequencing has incremental value in the diagnostic work-up of patients with suspect pancreatic masses; a multi-center prospective cross sectional study.

Background: The diagnostic process of patients with suspect pancreatic lesions is often lengthy and prone to repeated diagnostic procedures due to inconclusive results. Targeted Next-Generation Sequencing (NGS) performed on cytological material obtained with fine needle aspiration (FNA) or biliary duct brushing can speed up this process. Here, we study the incremental value of NGS for establishing the correct diagnosis, and subsequent treatment plan in patients with inconclusive diagnosis after regular diagnostic work-up for suspect pancreatic lesions.

The yield of staging laparoscopy for resectable and borderline resectable pancreatic cancer in the PREOPANC randomized controlled trial.

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 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.

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

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.

GITR Ligation Improves Anti-PD1-Mediated Restoration of Human MMR-Proficient Colorectal Carcinoma Tumor-Derived T Cells.

Background & Aims: In contrast to mismatch repair deficient colorectal carcinoma (CRC), MMR proficient (pMMR) CRC does not respond to immune checkpoint blockade. We studied immune checkpoint stimulation via glucocorticoid-induced tumor necrosis factor receptor-related protein (GITR) on ex vivo functionality of human tumor-infiltrating lymphocytes (TIL) isolated from pMMR primary CRC and liver metastases (CRLM).

Methods: Using lymphocytes from resected tumor, adjacent tissues, and peripheral blood mononuclear cells (PBMC) of 132 pMMR primary CRC or CRLM patients, we determined GITR expression and the in vitro T-cell agonistic activity of recombinant GITR ligation.

Bihormonal Artificial Pancreas With Closed-Loop Glucose Control vs Current Diabetes Care After Total Pancreatectomy: A Randomized Clinical Trial.

Importance: Glucose control in patients after total pancreatectomy is problematic because of the complete absence of α- and β-cells, leading to impaired quality of life. A novel, bihormonal artificial pancreas (BIHAP), using both insulin and glucagon, may improve glucose control, but studies in this setting are lacking.

Objective: To assess the efficacy and safety of the BIHAP in patients after total pancreatectomy.

Recurrent Disease After Esophageal Cancer Surgery: A Substudy of The Dutch Nationwide Ivory Study.

Objective: This study investigated the patterns, predictors, and survival of recurrent disease following esophageal cancer surgery.

Background: Survival of recurrent esophageal cancer is usually poor, with limited prospects of remission.

Methods: This nationwide cohort study included patients with distal esophageal and gastroesophageal junction adenocarcinoma and squamous cell carcinoma after curatively intended esophagectomy in 2007 to 2016 (follow-up until January 2020).

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

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.