H19 promotes polarization and alternative splicing in tumor-associated macrophages, facilitating pancreatic cancer progression.

Tumor-associated macrophages (TAMs) play a crucial physiological role in the pancreatic tumor microenvironment. However, the role of long non-coding RNAs (lncRNAs) in TAMs within pancreatic tumors remains unclear. By lncRNA sequencing between TAMs and resident macrophages from normal tissues in pancreatic cancer, it is found that H19 is highly expressed in TAMs and is correlated with the prognosis and stages of pancreatic cancer.

Effects of Pancreatic Fistula After Minimally Invasive and Open Pancreatoduodenectomy.

Importance: Postoperative pancreatic fistulas (POPF) are the biggest contributor to surgical morbidity and mortality after pancreatoduodenectomy. The impact of POPF could be influenced by the surgical approach.

Objective: To assess the clinical impact of POPF in patients undergoing minimally invasive pancreatoduodenectomy (MIPD) and open pancreatoduodenectomy (OPD).

Competency, Proficiency, and Mastery: Learning Curves for Robotic Distal Pancreatectomy at 16 International Expert Centers.

Objective: The aim of this study was to evaluate the different phases of the learning curve for robotic distal pancreatectomy (RDP) in international expert centers.

Summary Background Data: RDP is an emerging minimally invasive approach; however, only limited, mostly single center data are available on its safe implementation, including the learning curve.

Methods: Consecutive patients undergoing elective RDP from 16 expert centers across three continents were included to assess the learning curve.

The proinflammatory status, based on preoperative interleukin-6, predicts postpancreatectomy acute pancreatitis and associated postoperative pancreatic fistula after pancreaticoduodenectomy.

Background And Aim: Early predictors of morbidity after pancreaticoduodenectomy (PD) can guide tailored postoperative management. Preoperative inflammatory data in patients who underwent PD remained poorly studied in investigating the clinical significance of predicting postpancreatectomy acute pancreatitis (PPAP) and PPAP-associated postoperative pancreatic fistula (POPF).

Methods: The clinical data of 467 patients receiving PD between January 2020 and December 2022 were retrospectively reviewed.

Impact of patient age on outcome of minimally invasive versus open pancreatoduodenectomy: a propensity score matched study.

Background: Pancreatoduodenectomy in elderly patients may be associated with increased postoperative mortality, but studies in minimally invasive pancreatoduodenectomy (MIPD) are scarce.

Methods: International multicenter retrospective study including patients aged >60 years undergoing MIPD (robot-assisted and laparoscopic) and open pancreatoduodenectomy (OPD), were categorized by age: 60-69, 70-79, and 80+ years. In each category, propensity score matching (PSM) was performed (1:1 ratio) between MIPD and OPD.

Notch signaling regulates macrophage-mediated inflammation in metabolic dysfunction-associated steatotic liver disease.

The liver macrophage population comprises resident Kupffer cells (KCs) and monocyte-derived macrophages with distinct pro- or anti-inflammatory properties that affect the severity and course of liver diseases. The mechanisms underlying macrophage differentiation and functions in metabolic dysfunction-associated steatotic liver disease and/or steatohepatitis (MASLD/MASH) remain mostly unknown. Using single-cell RNA sequencing (scRNA-seq) and fate mapping of hepatic macrophage subpopulations, we unraveled the temporal and spatial dynamics of distinct monocyte and monocyte-derived macrophage subsets in MASH.

Gasdermin C promotes Stemness and Immune Evasion in Pancreatic Cancer via Pyroptosis-Independent Mechanism.

Pancreatic ductal adenocarcinoma (PDAC) is a highly metastatic and lethal disease. Gasdermins are primarily associated with necrosis via membrane permeabilization and pyroptosis, a lytic pro-inflammatory type of cell death. In this study, GSDMC upregulation during PDAC progression is reported.

CTC-derived pancreatic cancer models serve as research tools and are suitable for precision medicine approaches.

Pancreatic ductal adenocarcinoma (PDAC) poses significant clinical challenges, often presenting as unresectable with limited biopsy options. Here, we show that circulating tumor cells (CTCs) offer a promising alternative, serving as a "liquid biopsy" that enables the generation of in vitro 3D models and highly aggressive in vivo models for functional and molecular studies in advanced PDAC. Within the retrieved CTC pool (median 65 CTCs/5 mL), we identify a subset (median content 8.

Driver mutation subtypes involve with differentiated immunophenotypes influencing pancreatic cancer outcomes.

Despite many studies focusing on the prognostic biomarkers in pancreatic adenocarcinomas (PAADs), there is ill-informed about the relationships between their genomic features and immune characteristics. Herein, we deeply investigated the involvement of major driver mutation subtypes with immunophenotypes impacting PAAD outcomes. Based on public data analyses of RNA expression-based immune subtypes in PAAD, in contrast to KRAS G12D & TP53 co-mutant patients with poor outcomes, the best immune subtype C3 (inflammatory) characterized by high Th1/Th2 ratio was relatively enriched in KRASTP53 patients with better survival, whereas the inferior subtype C2 (IFN-γ dominant) with low Th1/Th2 ratio was more common in the former than in the latter.

Comprehensive analysis of KLF family reveals KLF6 as a promising prognostic and immune biomarker in pancreatic ductal adenocarcinoma.

Background: Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest tumors worldwide, with extremely aggressive and complicated biology. Krüppel-like factors (KLFs) encode a series of transcriptional regulatory proteins and play crucial roles in a variety of processes, including tumor cell differentiation and proliferation. However, the potential biological functions and possible pathways of KLFs in the progression of PDAC remain elusive.

Pan-cancer analysis implicates novel insights of lactate metabolism into immunotherapy response prediction and survival prognostication.

Background: Immunotherapy has emerged as a potent clinical approach for cancer treatment, but only subsets of cancer patients can benefit from it. Targeting lactate metabolism (LM) in tumor cells as a method to potentiate anti-tumor immune responses represents a promising therapeutic strategy.

Methods: Public single-cell RNA-Seq (scRNA-seq) cohorts collected from patients who received immunotherapy were systematically gathered and scrutinized to delineate the association between LM and the immunotherapy response.

Tumor cell-intrinsic epigenetic dysregulation shapes cancer-associated fibroblasts heterogeneity to metabolically support pancreatic cancer.

The tumor microenvironment (TME) in pancreatic ductal adenocarcinoma (PDAC) involves a significant accumulation of cancer-associated fibroblasts (CAFs) as part of the host response to tumor cells. The origins and functions of transcriptionally diverse CAF populations in PDAC remain poorly understood. Tumor cell-intrinsic genetic mutations and epigenetic dysregulation may reshape the TME; however, their impacts on CAF heterogeneity remain elusive.

Characterization of Pancreatic Fistula after Post-pancreatectomy Acute Pancreatitis.

Objective: This study aimed to investigate the clinical significance and risk factors of postoperative pancreatic fistula (POPF) after post-pancreatectomy acute pancreatitis (PPAP) in patients who underwent pancreaticoduodenectomy (PD).

Summary Background Data: PPAP has been recognized as a critical factor in the pathophysiology of POPF after PD.

Methods: A total of 817 consecutive patients who underwent elective PD between January 2020 and June 2022 were included.

The Effect of Perioperative Dexamethasone on Postoperative Complications After Pancreaticoduodenectomy: A Multicenter Randomized Controlled Trial.

Objective: To evaluate the effect of perioperative dexamethasone on postoperative complications after pancreaticoduodenectomy.

Background: The glucocorticoid dexamethasone has been shown to improve postoperative outcomes in surgical patients, but its effects on postoperative complications after pancreaticoduodenectomy are unclear.

Methods: This multicenter, double-blind, randomized controlled trial was conducted in four Chinese high-volume pancreatic centers.

Prospective observational study on biomarkers of response in pancreatic ductal adenocarcinoma.

Adjuvant chemotherapy benefits patients with resected pancreatic ductal adenocarcinoma (PDAC), but the compromised physical state of post-operative patients can hinder compliance. Biomarkers that identify candidates for prompt adjuvant therapy are needed. In this prospective observational study, 1,171 patients with PDAC who underwent pancreatectomy were enrolled and extensively followed-up.

Short-term and Long-term Outcomes of Robotic Enucleation of Tumors Located in the Pancreatic Head and Uncinate Process.

Objective: To assess short-term and long-term outcomes following robotic enucleation (REn) of tumors in the proximal pancreas.

Background: Despite the advantages of preserving function via pancreatic enucleation, controversies persist, since this can be associated with severe complications, such as clinically relevant postoperative pancreatic fistula, especially when performed near the main pancreatic duct. The safety and efficacy of REn in this context remain largely unknown.

Immunogram defines four cancer-immunity cycle phenotypes with distinct clonal selection patterns across solid tumors.

Background: The cancer-immunity cycle (CI cycle) provides a theoretical framework to illustrate the process of the anticancer immune response. Recently, the update of the CI cycle theory emphasizes the importance of tumor's immunological phenotype. However, there is lack of immunological phenotype of pan-cancer based on CI cycle theory.

Deterministic reprogramming of neutrophils within tumors.

Neutrophils are increasingly recognized as key players in the tumor immune response and are associated with poor clinical outcomes. Despite recent advances characterizing the diversity of neutrophil states in cancer, common trajectories and mechanisms governing the ontogeny and relationship between these neutrophil states remain undefined. Here, we demonstrate that immature and mature neutrophils that enter tumors undergo irreversible epigenetic, transcriptional, and proteomic modifications to converge into a distinct, terminally differentiated dcTRAIL-R1 state.

ATF3-induced activation of NF-κB pathway results in acquired PARP inhibitor resistance in pancreatic adenocarcinoma.

Purpose: Olaparib, an inhibitor of poly-(adenosine diphosphate-ribose) polymerase (PARP), has been shown to have anticancer benefits in patients with pancreatic cancer who have a germline mutation in BRCA1/2. However, resistance acquired on long-term exposure to olaparib significantly impedes clinical efficacy.

Methods: In this study, the chromatin accessibility and differentially expressed transcripts of parental and olaparib-resistant pancreatic cancer cell lines were assessed using the Assay for Transposase Accessible Chromatin with sequencing (ATAC-seq) and mRNA-seq.

Robotic versus open pancreatoduodenectomy in patients with pancreatic duct adenocarcinoma after the learning curve: a propensity score-matched analysis.

Background: Studies have demonstrated that the learning curve plays an important role in robotic pancreatoduodenectomy (RPD). Although improved short-term outcomes of RPD after the learning curve have been reported compared to open pancreatoduodenectomy (OPD), there is a lack of long-term survival analyses.

Methods: Patients who underwent curative intended RPD and OPD for pancreatic duct adenocarcinoma (PDAC) between January 2017 and June 2020 were retrospectively reviewed.

BHLHE40 Inhibits Ferroptosis in Pancreatic Cancer Cells via Upregulating SREBF1.

Pancreatic cancer (PCa) is one of the most fatal human malignancies. The enhanced infiltration of stromal tissue into the PCa tumor microenvironment limits the identification of key tumor-specific transcription factors and epigenomic abnormalities in malignant epithelial cells. Integrated transcriptome and epigenetic multiomics analyses of the paired PCa organoids indicate that the basic helix-loop-helix transcription factor 40 (BHLHE40) is significantly upregulated in tumor samples.