An anti-CEA affibody showing high-definition staining in human pancreatic cancer tissue sections and selective tumor targeting in vivo.

We report development and characterization of small non-immunoglobulin affibody affinity proteins directed to the highly glycosylated human carcinoembryonic antigen-related adhesion molecule 5 (CEACAM5, CEA), and their use in immunohistochemical (IHC) analyses of human pancreatic cancer samples and for in vivo tumor imaging. A total of nineteen unique anti-CEA affibodies were identified from large phage display libraries constructed using combinatorial protein engineering of a small 58 amino acid three-helix bundle protein domain. Molecular modeling suggested that all enriched clones share a binding surface with several clustered tryptophan residues interacting with a hydrophobic patch in the N1 domain of CEA centered around a phenylalanine residue.

Performance of MRI-based surveillance for high-risk individuals for pancreatic cancer.

Purpose: Surveillance is recommended in high-risk individuals (HRIs) for pancreatic cancer (PC), as it seems effective in detecting malignant/premalignant lesions. Most surveillance programs are based on a combination of MRI and endoscopic ultrasound. This study aimed to evaluate the incidence of relevant imaging findings (PC and lesions with high-grade dysplasia) and the performance of MRI-based surveillance in a single-centre HRIs cohort.

Pediatric Autoimmune Pancreatitis: Clinical Findings and Outcomes in Sweden.

Introduction: Pediatric autoimmune pancreatitis (AIP) is a rare form of pancreatitis in children with poorly understood pathophysiology. It is a recognized risk factor for chronic pancreatitis in approximately 4% of pediatric cases. This study aims to describe the demographics, clinical characteristics, and outcomes of a large Swedish cohort of pediatric AIP patients.

Histological Subtypes Might Help Risk Stratification in Different Morphological Types of IPMNs: Back to the Future?

Intraductal papillary mucinous neoplasms (IPMNs) display four histological subtypes: gastric foveolar, pancreaticobiliary, intestinal, and oncocytic. All of these subtypes harbor a different risk of cancer development. The clinical impact of these subtypes concerning the occurrence of high-grade dysplasia (HGD)/cancer (C) in specific morphological types, such as branch-duct (BD), main-duct (MD), and mixed-type (MT) IPMNs, has been less investigated.

Cellular spartans at the pass: Emerging intricacies of cell competition in early and late tumorigenesis.

Cell competition is a mechanism for cellular quality control based on cell-cell comparisons of fitness. Recent studies have unveiled a central and complex role for cell competition in cancer. Early tumors exploit cell competition to replace neighboring normal epithelial cells.

Histopathological growth patterns and tumor-infiltrating lymphocytes in breast cancer liver metastases.

Liver is the third most common organ for breast cancer (BC) metastasis. Two main histopathological growth patterns (HGP) exist in liver metastases (LM): desmoplastic and replacement. Although a reduced immunotherapy efficacy is reported in patients with LM, tumor-infiltrating lymphocytes (TIL) have not yet been investigated in BCLM.

An idiosyncratic zonated stroma encapsulates desmoplastic liver metastases and originates from injured liver.

A perimetastatic capsule is a strong positive prognostic factor in liver metastases, but its origin remains unclear. Here, we systematically quantify the capsule's extent and cellular composition in 263 patients with colorectal cancer liver metastases to investigate its clinical significance and origin. We show that survival improves proportionally with increasing encapsulation and decreasing tumor-hepatocyte contact.

Liver Transplantation for Liver Metastasis of a Pseudopapillary Pancreatic Neoplasm in a Male Patient.

BACKGROUND Solid pseudopapillary neoplasm (SPN) of the pancreas, which predominantly affects young women, is an uncommon condition with low malignant potential. It is often asymptomatic. This tumor has a low metastatic rate and a good prognosis in contrast to other pancreatic tumors.

FPR2 Shapes an Immune-Excluded Pancreatic Tumor Microenvironment and Drives T-cell Exhaustion in a Sex-Dependent Manner.

Unlabelled: Sex-driven immune differences can affect tumor progression and the landscape of the tumor microenvironment. Deeper understanding of these differences in males and females can inform patient selection to improve sex-optimized immunotherapy treatments. In this study, single-cell RNA sequencing and protein analyses uncovered a subpopulation of myeloid cells in pancreatic lesions associated with an immune-excluded tumor phenotype and effector T-cell exhaustion exclusively in females.

Fibrosis-Related Gene Profiling in Liver Biopsies of PiZZ α1-Antitrypsin Children with Different Clinical Courses.

PiZZ (Glu342Lys) α1-antitrypsin deficiency (AATD) is characterized by intrahepatic AAT polymerization and is a risk factor for liver disease development in children. The majority of PiZZ children are disease free, hence this mutation alone is not sufficient to cause the disease. We investigated Z-AAT polymers and the expression of fibrosis-related genes in liver tissues of PiZZ children with different clinical courses.

Exploration of Patient-Derived Pancreatic Ductal Adenocarcinoma Ex Vivo Tissue for Treatment Response.

Patient-derived tissue culture models are valuable tools to investigate drug effects and targeted treatment approaches. Resected tumor slices cultured ex vivo have recently gained interest in precision medicine, since they reflect the complex microenvironment of cancer tissue. In this study, we examined the treatment response to an internally developed ex vivo tissue culture model from pancreatic ductal adenocarcinoma (PDAC) and in vitro analysis.

Drug-induced tumor-specific cytotoxicity in a whole tissue model of human pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is the most common type of pancreatic cancer. PDAC has a dismal prognosis and an inherent resistance to cytostatic drugs. The lack of reliable experimental models is a severe limitation for drug development targeting PDAC.

Chemokine Receptor Expression on T Cells Is Modulated by CAFs and Chemokines Affect the Spatial Distribution of T Cells in Pancreatic Tumors.

The accumulation of T cells is associated with a better prognosis in pancreatic cancer. However, the immunosuppressive tumor microenvironment, largely composed by cancer-associated fibroblasts (CAFs), can prevent T cells from reaching the tumor nests. We examined how human CAFs modulated chemokine receptors known to be associated with T cell trafficking, CXCR3 and CCR5, and T cell exclusion, CXCR4.

Histopathological growth patterns of liver metastasis: updated consensus guidelines for pattern scoring, perspectives and recent mechanistic insights.

The first consensus guidelines for scoring the histopathological growth patterns (HGPs) of liver metastases were established in 2017. Since then, numerous studies have applied these guidelines, have further substantiated the potential clinical value of the HGPs in patients with liver metastases from various tumour types and are starting to shed light on the biology of the distinct HGPs. In the present guidelines, we give an overview of these studies, discuss novel strategies for predicting the HGPs of liver metastases, such as deep-learning algorithms for whole-slide histopathology images and medical imaging, and highlight liver metastasis animal models that exhibit features of the different HGPs.

Unraveling the relationship between autoimmune pancreatitis type 2 and inflammatory bowel disease: Results from two centers and systematic review of the literature.

Introduction: The relationship between autoimmune pancreatitis (AIP) type 2 and inflammatory bowel disease (IBD) has been established and previously described within International Consensus Diagnostic Criteria. However, it is unknown if the presence of IBD changes the natural disease course of AIP type 2. Our aim was to investigate the association between AIP type 2 and IBD as well as to systematically summarize all the existing evidence in the literature.

Redefining resection margins and dissection planes in perihilar cholangiocarcinoma-radical resection is a rare event.

Radical tumor resection (pR0) is prognostic for disease-free and overall survival after resection of perihilar cholangiocarcinoma (pCCA). However, no universal agreement exists on the definition of radical resection and histopathological reporting. The aim of this study was to provide a standardized protocol for histopathological assessment and reporting of the surgical specimen obtained after resection for pCCA.