Intersurgeon Variability in Local Treatment Planning for Patients with Initially Unresectable Colorectal Cancer Liver Metastases: Analysis of the Liver Expert Panel of the Dutch Colorectal Cancer Group.

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.

The role of tumour biological factors in technical anatomical resectability assessment of colorectal liver metastases following induction systemic treatment: An analysis of the Dutch CAIRO5 trial.

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.

Long-term follow-up of a randomized trial of biliary drainage in perihilar cholangiocarcinoma.

Background And Aims: The DRAINAGE trial was a randomized controlled trial comparing preoperative endoscopic (EBD) and percutaneous biliary drainage (PTBD) in patients with potentially resectable, perihilar cholangiocarcinoma (pCCA). The aim of this study was to compare the long-term outcomes.

Methods: Patients were randomized in four tertiary referral centers.

Defining Textbook Outcome in liver surgery and assessment of hospital variation: A nationwide population-based study.

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 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.

Interobserver Variability in CT-based Morphologic Tumor Response Assessment of Colorectal Liver Metastases.

Purpose To evaluate interobserver variability in the morphologic tumor response assessment of colorectal liver metastases (CRLM) managed with systemic therapy and to assess the relation of morphologic response with gene mutation status, targeted therapy, and Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 measurements. Materials and Methods Participants with initially unresectable CRLM receiving different systemic therapy regimens from the randomized, controlled CAIRO5 trial (NCT02162563) were included in this prospective imaging study.

The orange-III study: the use of preoperative laxatives prior to liver surgery in an enhanced recovery programme, a randomized controlled trial.

Background: This study evaluates the effect of preoperative macrogol on gastrointestinal recovery and functional recovery after liver surgery combined with an enhanced recovery programme in a randomized controlled setting.

Methods: Patients were randomized to either 1 sachet of macrogol a day, one week prior to surgery versus no preoperative laxatives. Postoperative management for all patients was within an enhanced recovery programme.

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

Background: Somatostatin analogues (SA) are currently used to prevent postoperative pancreatic fistula (POPF) development. However, its use is controversial. This study investigated the effect of different SA protocols on the incidence of POPF after pancreatoduodenectomy in a nationwide population.

Combined Quantitative (Phospho)proteomics and Mass Spectrometry Imaging Reveal Temporal and Spatial Protein Changes in Human Intestinal Ischemia-Reperfusion.

Intestinal ischemia-reperfusion (IR) injury is a severe clinical condition, and unraveling its pathophysiology is crucial to improve therapeutic strategies and reduce the high morbidity and mortality rates. Here, we studied the dynamic proteome and phosphoproteome in the human intestine during ischemia and reperfusion, using liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis to gain quantitative information of thousands of proteins and phosphorylation sites, as well as mass spectrometry imaging (MSI) to obtain spatial information. We identified a significant decrease in abundance of proteins related to intestinal absorption, microvillus, and cell junction, whereas proteins involved in innate immunity, in particular the complement cascade, and extracellular matrix organization increased in abundance after IR.

Temporal Transcript Profiling Identifies a Role for Unfolded Protein Stress in Human Gut Ischemia-Reperfusion Injury.

Background & Aims: Intestinal ischemia-reperfusion injury is a serious and life-threatening condition. A better understanding of molecular mechanisms related to intestinal ischemia-reperfusion injury in human beings is imperative to find therapeutic targets and improve patient outcome.

Methods: First, the in vivo dynamic modulation of mucosal gene expression of the ischemia-reperfusion-injured human small intestine was studied.

The Prognostic Value of Total Tumor Volume Response Compared With RECIST1.1 in Patients With Initially Unresectable Colorectal Liver Metastases Undergoing Systemic Treatment.

Objectives: Compare total tumor volume (TTV) response after systemic treatment to Response Evaluation Criteria in Solid Tumors (RECIST1.1) and assess the prognostic value of TTV change and RECIST1.1 for recurrence-free survival (RFS) in patients with colorectal liver-only metastases (CRLM).

Immediate versus Postponed Intervention for Infected Necrotizing Pancreatitis.

Background: Infected necrotizing pancreatitis is a potentially lethal disease that is treated with the use of a step-up approach, with catheter drainage often delayed until the infected necrosis is encapsulated. Whether outcomes could be improved by earlier catheter drainage is unknown.

Methods: We conducted a multicenter, randomized superiority trial involving patients with infected necrotizing pancreatitis, in which we compared immediate drainage within 24 hours after randomization once infected necrosis was diagnosed with drainage that was postponed until the stage of walled-off necrosis was reached.

Bile Salt and FGF19 Signaling in the Early Phase of Human Liver Regeneration.

The involvement of bile salt-fibroblast growth factor 19 (FGF19) signaling in human liver regeneration (LR) is not well studied. Therefore, we studied aspects of bile salt-FGF19 signaling shortly after liver resection in patients. We compared plasma bile salt and FGF19 levels in arterial, portal and hepatic venous blood, calculated venous-arterial differences (ΔVA), and determined hepatic transcript levels on two intra-operative time points: before (< 1 hour) and immediately after (> 2-3 hours) liver resection (i.

Short-Term Outcomes of Secondary Liver Surgery for Initially Unresectable Colorectal Liver Metastases Following Modern Induction Systemic Therapy in the Dutch CAIRO5 Trial.

Objective: To present short-term outcomes of liver surgery in patients with initially unresectable colorectal liver metastases (CRLM) downsized by chemotherapy plus targeted agents.

Background: The increase of complex hepatic resections of CRLM, technical innovations pushing boundaries of respectability, and use of intensified induction systemic regimens warrant for safety data in a homogeneous multicenter prospective cohort.

Methods: Patients with initially unresectable CRLM, who underwent complete resection after induction systemic regimens with doublet or triplet chemotherapy, both plus targeted therapy, were selected from the ongoing phase III CAIRO5 study (NCT02162563).

Hepatocellular adenoma in men: A nationwide assessment of pathology and correlation with clinical course.

Background & Aims: Hepatocellular adenomas (HCA) rarely occur in males, and if so, are frequently associated with malignant transformation. Guidelines are based on small numbers of patients and advise resection of HCA in male patients, irrespective of size or subtype. This nationwide retrospective cohort study is the largest series of HCA in men correlating (immuno)histopathological and molecular findings with the clinical course.

Evaluating the safety of two human experimental intestinal ischemia reperfusion models: A retrospective observational study.

Background: We developed a jejunal and colonic experimental human ischemia-reperfusion (IR) model to study pathophysiological intestinal IR mechanisms and potential new intestinal ischemia biomarkers. Our objective was to evaluate the safety of these IR models by comparing patients undergoing surgery with and without in vivo intestinal IR.

Methods: A retrospective study was performed comparing complication rates and severity, based on the Clavien-Dindo classification system, in patients undergoing pancreatoduodenectomy with (n = 10) and without (n = 20 matched controls) jejunal IR or colorectal surgery with (n = 10) and without (n = 20 matched controls) colon IR.

Ectopic fat in liver and skeletal muscle is associated with shorter overall survival in patients with colorectal liver metastases.

Background: Myosteatosis has been associated with shorter overall survival in cancer patients. The increase in ectopic fat might not be limited to skeletal muscle only and might also extend to other sites such as the liver, resulting in non-alcoholic fatty liver disease (NAFLD). In this study, we assessed the relationship between myosteatosis and NAFLD and their association with overall survival in patients with colorectal liver metastases undergoing partial hepatectomy.

A population-based study on incidence, treatment, and survival in ampullary cancer in the Netherlands.

Introduction: Ampullary cancer is rare and as a result epidemiological data are scarce. The aim of this population-based study was to determine the trends in incidence, treatment and overall survival (OS) in patients with ampullary adenocarcinoma in the Netherlands between 1989 and 2016.

Methods: Patients diagnosed with ampullary adenocarcinoma were identified from the Netherlands Cancer Registry.

Complications After Major Surgery for Duodenopancreatic Neuroendocrine Tumors in Patients with MEN1: Results from a Nationwide Cohort.

Background: Little is known about complications after major duodenopancreatic surgery for duodenopancreatic neuroendocrine tumors (dpNETs) in multiple endocrine neoplasia type 1 (MEN1). Therefore, the incidence and severity of complications after major surgery for MEN1-related dpNETs were assessed.

Methods: Patients were selected from the population-based Dutch MEN1 database if they had undergone a Whipple procedure or total pancreatectomy from 2003 to 2017.

Proteomics analysis of human intestinal organoids during hypoxia and reoxygenation as a model to study ischemia-reperfusion injury.

Intestinal ischemia-reperfusion (IR) injury is associated with high mortality rates, which have not improved in the past decades despite advanced insight in its pathophysiology using in vivo animal and human models. The inability to translate previous findings to effective therapies emphasizes the need for a physiologically relevant in vitro model to thoroughly investigate mechanisms of IR-induced epithelial injury and test potential therapies. In this study, we demonstrate the use of human small intestinal organoids to model IR injury by exposing organoids to hypoxia and reoxygenation (HR).

Reliability and Agreement of Radiological and Pathological Tumor Size in Patients with Multiple Endocrine Neoplasia Type 1-Related Pancreatic Neuroendocrine Tumors: Results from a Population-Based Cohort.

Background: Pancreatic neuroendocrine tumors (pNETs) have a high prevalence in patients with multiple endocrine neoplasia type 1 (MEN1) and are the leading cause of death. Tumor size is still regarded as the main prognostic factor and therefore used for surgical decision-making. We assessed reliability and agreement of radiological and pathological tumor size in a population-based cohort of patients with MEN1-related pNETs.

Resectability and Ablatability Criteria for the Treatment of Liver Only Colorectal Metastases: Multidisciplinary Consensus Document from the COLLISION Trial Group.

The guidelines for metastatic colorectal cancer crudely state that the best local treatment should be selected from a 'toolbox' of techniques according to patient- and treatment-related factors. We created an interdisciplinary, consensus-based algorithm with specific resectability and ablatability criteria for the treatment of colorectal liver metastases (CRLM). To pursue consensus, members of the multidisciplinary COLLISION and COLDFIRE trial expert panel employed the RAND appropriateness method (RAM).

Choledochal malformations in adults in the Netherlands: Results from a nationwide retrospective cohort study.

Background And Aims: Patients with a choledochal malformation, formerly described as cysts, are at increased risk of developing a cholangiocarcinoma and resection is recommended. Given the low incidence of choledochal malformation (CM) in Western countries, the incidence in these countries is unclear. Our aim was to assess the incidence of malignancy in CM patients and to assess postoperative outcome.

Paneth Cell Alterations During Ischemia-reperfusion, Follow-up, and Graft Rejection After Intestinal Transplantation.

Background: Ischemia-reperfusion injury is inevitable during intestinal transplantation (ITx) and executes a key role in the evolution towards rejection. Paneth cells (PCs) are crucial for epithelial immune defense and highly vulnerable to ischemia-reperfusion injury. We investigated the effect of ITx on PC after reperfusion (T0), during follow-up, and rejection.

Enhanced recovery after surgery programmes in older patients undergoing hepatopancreatobiliary surgery: what benefits might prehabilitation have?

Due to an aging population and the related growing number of less physically fit patients with multiple comorbidities, adequate perioperative care is a new and rapidly developing clinical science that is becoming increasingly important. This narrative review focuses on enhanced recovery after surgery (ERAS®) programmes and the growing interest in prehabilitation programmes to improve patient- and treatment-related outcomes in older patients undergoing hepatopancreatobiliary (HPB) surgery. Future steps required in the further development of optimal perioperative care in HPB surgery are also discussed.