Spatial lipidomics reveals sphingolipid metabolism as anti-fibrotic target in the liver.

Background And Aims: Steatotic liver disease (SLD), which encompasses various causes of fat accumulation in the liver, is a major cause of liver fibrosis. Understanding the specific mechanisms of lipotoxicity, dysregulated lipid metabolism, and the role of different hepatic cell types involved in fibrogenesis is crucial for therapy development.

Methods: We analysed liver tissue from SLD patients and 3 mouse models.

Pharmacological manipulation of liver fibrosis progression using novel HDAC6 inhibitors.

Chronic liver injury characterized by unresolved hepatitis leads to fibrosis, potentially progressing to cirrhosis and hepatocellular carcinoma. Effective treatments for halting or reversing liver fibrosis are currently lacking. This study investigates the potential of HDAC6 as a therapeutic target in liver fibrosis.

Unveiling hidden outcomes in malignant gastric outlet obstruction research - insights from a "Pancreas 2000" review.

Malignant gastric outlet obstruction (mGOO) is a major condition affecting patients with periampullary tumors, including pancreatic cancer. The current treatment options include surgical gastroenterostomy, endoscopic stenting and more recently EUS-guided gastroenterostomy. Most studies comparing the outcomes of the three procedures focus on technical success, clinical success and safety.

Management of malignant Gastric Outlet Obstruction (mGOO) due to pancreatic cancer in the era of EUS-Gastrojejunostomy: an international practice survey and case vignette study by Pancreas 2000 from the European Pancreatic Club.

Background: Malignant Gastric Outlet Obstruction (mGOO) has been standardly treated by surgical Gastrojejunostomy (S-GJ) or Endoscopic Stenting (ES). Recently, EUS-Gastrojejunostomy (EUS-GJ) has emerged as an alternative, despite its worldwide diffusion is heterogeneous. The aim of this survey was to assess clinical decision-making around mGOO and to explore current opinions regarding EUS-GJ.

Is aggressive intravenous fluid prescription the answer to reduce mortality in severe pancreatitis? The FLIP study: Fluid resuscitation in pancreatitis.

Backgrounds/aims: Acute pancreatitis is an emergency presentation, which can range from mild to life threatening. Intravenous fluids are the cornerstone of management. Although the WATERFALL trial described the optimal fluid rate in mild/moderate pancreatitis, this trial excluded patients with moderate-severe/severe pancreatitis.

COVID-19 and liver cancer: lost patients and larger tumours.

Background: Northern England has been experiencing a persistent rise in the number of primary liver cancers, largely driven by an increasing incidence of hepatocellular carcinoma (HCC) secondary to alcohol-related liver disease and non-alcoholic fatty liver disease. Here we review the effect of the COVID-19 pandemic on primary liver cancer services and patients in our region.

Objective: To assess the impact of the COVID-19 pandemic on patients with newly diagnosed liver cancer in our region.

Impact of routine nasogastric decompression versus no nasogastric decompression after pancreaticoduodenectomy on perioperative outcomes: meta-analysis.

Background: Consensus on the use of nasogastric decompression (NGD) after pancreaticoduodenectomy (PD) is lacking. This meta-analysis reviewed current evidence on the impact of routine NGD versus no NGD after PD on perioperative outcomes.

Methods: PubMed, Medline, Scopus, Embase and Cochrane databases were searched for studies reporting on the role of NGD after PD on perioperative outcomes.

Non-invasive synchronous monitoring of neutrophil migration using whole body near-infrared fluorescence-based imaging.

Advances in fluorescence imaging coupled with the generation of near infrared probes have significantly improved the capabilities of non-invasive, real-time imaging in whole animals. In this study we were able to overcome a limitation of in vivo fluorescence imaging and have established a dual cell tracking method where two different cell types can be monitored according to the spectral signature of the cell labelling fluorophore. Using a mouse model of acute liver injury, we have characterised the in vivo migration patterns of wild type and transgenic neutrophils with impaired chemotaxis.

RNA sequencing reveals changes in the microRNAome of transdifferentiating hepatic stellate cells that are conserved between human and rat.

MicroRNAs are small (~ 22nt long) noncoding RNAs (ncRNAs) that regulate gene expression at the post-transcriptional level. Over 2000 microRNAs have been described in humans and many are implicated in human pathologies including tissue fibrosis. Hepatic stellate cells (HSC) are the major cellular contributors to excess extracellular matrix deposition in the diseased liver and as such are important in the progression of liver fibrosis.

c-Rel orchestrates energy-dependent epithelial and macrophage reprogramming in fibrosis.

Fibrosis is a common pathological feature of chronic disease. Deletion of the NF-κB subunit c-Rel limits fibrosis in multiple organs, although the mechanistic nature of this protection is unresolved. Using cell-specific gene-targeting manipulations in mice undergoing liver damage, we elucidate a critical role for c-Rel in controlling metabolic changes required for inflammatory and fibrogenic activities of hepatocytes and macrophages and identify Pfkfb3 as the key downstream metabolic mediator of this response.

Therapeutic Strategies Toward Lactate Dehydrogenase Within the Tumor Microenvironment of Pancreatic Cancer.

Objectives: Pancreatic stellate cells (PSCs) play a key metabolic role within the tumor microenvironment (stroma) of pancreatic ductal adenocarcinoma (PDAC), being glycolytic and associated with protumorigenic acidification from excess lactate. This study investigates the clinical significance of glycolytic enzyme lactate dehydrogenase (LDH) and determines efficacy of the novel pan-LDH inhibitor Galloflavin.

Methods: An in vitro Transwell system was adopted for coculture of PSCs and 3 PDAC cell lines (MIA PaCa-2, PANC-1, and BxPC-3).

Role of Pre-operative Inflammatory Markers as Predictors of Lymph Node Positivity and Disease Recurrence in Well-Differentiated Pancreatic Neuroendocrine Tumours: Pancreas2000 Research and Educational Program (Course 9).

Pancreatic neuroendocrine tumours (PNET) is a rare disease and in the absence of metastases, surgical resection is recommended. Key factors affecting survival in PNETs are the stage and grade of the disease, but there is increasing evidence suggesting lymph node involvement is associated with shorter disease-free and overall survival. Ability to predict the likelihood of lymph node involvement at the time of diagnosis would affect surgical decision making in these patients.

Development and external validation of a prediction model for survival in patients with resected ampullary adenocarcinoma.

Introduction: Ampullary adenocarcinoma (AAC) is a rare malignancy with great morphological heterogeneity, which complicates the prediction of survival and, therefore, clinical decision-making. The aim of this study was to develop and externally validate a prediction model for survival after resection of AAC.

Materials And Methods: An international multicenter cohort study was conducted, including patients who underwent pancreatoduodenectomy for AAC (2006-2017) from 27 centers in 10 countries spanning three continents.

Epigenetic mechanisms and metabolic reprogramming in fibrogenesis: dual targeting of G9a and DNMT1 for the inhibition of liver fibrosis.

Objective: Hepatic stellate cells (HSC) transdifferentiation into myofibroblasts is central to fibrogenesis. Epigenetic mechanisms, including histone and DNA methylation, play a key role in this process. Concerted action between histone and DNA-mehyltransferases like G9a and DNMT1 is a common theme in gene expression regulation.

Past East Asian monsoon evolution controlled by paleogeography, not CO.

The East Asian monsoon plays an integral role in human society, yet its geological history and controlling processes are poorly understood. Using a general circulation model and geological data, we explore the drivers controlling the evolution of the monsoon system over the past 150 million years. In contrast to previous work, we find that the monsoon is controlled primarily by changes in paleogeography, with little influence from atmospheric CO.

Systemic inflammation contributes to impairment of quality of life in chronic pancreatitis.

Chronic pancreatitis (CP) is a fibrotic disorder of the pancreas leading to clinical sequelae like pain and an excess of comorbidity including cardiovascular disease and cancers. The aim of this study was to determine the relationship between systemic inflammation and quality of life in patients with CP. Patients were prospectively recruited and underwent a quality of life assessment (EORTC QLQ-C30 and PAN 28).

A Bioreactor Technology for Modeling Fibrosis in Human and Rodent Precision-Cut Liver Slices.

Precision cut liver slices (PCLSs) retain the structure and cellular composition of the native liver and represent an improved system to study liver fibrosis compared to two-dimensional mono- or co-cultures. The aim of this study was to develop a bioreactor system to increase the healthy life span of PCLSs and model fibrogenesis. PCLSs were generated from normal rat or human liver, or fibrotic rat liver, and cultured in our bioreactor.

Robotic versus conventional laparoscopic distal pancreatic resection: a systematic review and meta-analysis.

Background: Robotic surgery offers theoretical advantages to conventional laparoscopic surgery including improved instrument dexterity, 3D visualization and better ergonomics. This review aimed to determine if these theoretical advantages translate into improved patient outcomes in patients undergoing distal pancreatectomy through laparoscopic (LDP) or robotic (RDP) approaches.

Method: A systematic literature search was conducted for studies reporting minimally invasive surgery for distal pancreatectomy.

Robotic fenestration of massive liver cysts using EndoWrist technology.

Background: We present the short-term outcomes of robotic fenestration of symptomatic liver cysts using the EndoWrist One Vessel Sealer.

Methods: Data from patients who underwent robotic deroofing were collected and analysed retrospectively.

Results: A total of 17 patients were treated.

Histopathologic Predictors of Survival and Recurrence in Resected Ampullary Adenocarcinoma: International Multicenter Cohort Study.

Objective: The aim of the study was to define histopathologic characteristics that independently predict overall survival (OS) and disease-free survival (DFS), in patients who underwent resection of an ampullary adenocarcinoma with curative intent.

Summary Background Data: A broad range of survival rates have been described for adenocarcinoma of the ampulla of Vater, presumably due to morphological heterogeneity which is a result of the different epitheliums ampullary adenocarcinoma can arise from (intestinal or pancreaticobiliary). Large series with homogenous patient selection are scarce.

Vitamins D and K as Factors Associated with Osteopathy in Chronic Pancreatitis: A Prospective Multicentre Study (P-BONE Study).

Background: Osteopathy is common in patients with chronic pancreatitis (CP), but previous studies carry several limitations. Vitamin K is essential for bone metabolism, but its role in this setting has never been investigated. Our aim is to assess the prevalence of osteoporosis and osteopenia in CP patients, and to investigate the association between osteopathy and CP features and nutritional parameters, especially vitamin D and K levels.