UCHL1-dependent control of hypoxia-inducible factor transcriptional activity during liver fibrosis.

Liver fibrosis is the excessive accumulation of extracellular matrix proteins that occurs in most types of chronic liver disease. At the cellular level, liver fibrosis is associated with the activation of hepatic stellate cells (HSCs) which transdifferentiate into a myofibroblast-like phenotype that is contractile, proliferative and profibrogenic. HSC transdifferentiation induces genome-wide changes in gene expression that enable the cell to adopt its profibrogenic functions.

Assessment of inter-centre agreement across multidisciplinary team meetings for patients with retroperitoneal sarcoma.

Background: Decision-making in the management of patients with retroperitoneal sarcoma is complex and requires input from a number of different specialists. The aim of this study was to evaluate the levels of agreement in terms of resectability, treatment allocation, and organs proposed to be resected across different retroperitoneal sarcoma multidisciplinary team meetings.

Methods: The CT scans and clinical information of 21 anonymized retroperitoneal sarcoma patients were sent to all of the retroperitoneal sarcoma multidisciplinary team meetings in Great Britain, which were asked to give an opinion about resectability, treatment allocation, and organs proposed to be resected.

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 prior biliary stenting on diagnostic performance of endoscopic ultrasound for mesenteric vascular staging in patients with head of pancreas and periampullary malignancy.

Objective: The diagnostic performance of endoscopic ultrasound (EUS) for stratification of head of pancreas and periampullary tumours into resectable, borderline resectable and locally advanced tumours is unclear as is the effect of endobiliary stents. The primary aim of the study was to assess the diagnostic performance of EUS for resectability according to stent status.

Design: A retrospective study was performed.

A Mammalian Target of Rapamycin-Perilipin 3 (mTORC1-Plin3) Pathway is essential to Activate Lipophagy and Protects Against Hepatosteatosis.

Background And Aims: NAFLD is the most common hepatic pathology in western countries and no treatment is currently available. NAFLD is characterized by the aberrant hepatocellular accumulation of fatty acids in the form of lipid droplets (LDs). Recently, it was shown that liver LD degradation occurs through a process termed lipophagy, a form of autophagy.

A retrospective cohort study of nutritional status, nutritional interventions and hospital admissions in patients with chronic pancreatitis managed at a tertiary referral centre.

Purpose: Chronic pancreatitis (CP) is a complex disease process causing abdominal pain, diarrhoea and weight loss. The long-term nutritional implications however are not well documented. The aim of this study was to evaluate nutritional status in patients with CP over an extended time period and assess frequency and duration of CP related hospitalisation.

Systematic review and meta-analysis of risk factors of postoperative pancreatic fistula after distal pancreatectomy in the era of 2016 International Study Group pancreatic fistula definition.

Background: Risk factors for the development of clinically relevant POPF (CR-POPF) following distal pancreatectomy (DP) need clarification particularly following the 2016 International Study Group of Pancreatic Fistula (ISGPF) definition.

Methods: A systemic search of MEDLINE, Pubmed, Scopus, and EMBASE were conducted using the PRISMA framework. Studies were evaluated for risk factors for the development CR-POPF after DP using the 2016 ISGPF definition.

Novel multidisciplinary hub-and-spoke tertiary service for the management of severe acute pancreatitis.

Objective: Severe acute pancreatitis (SAP) is associated with high mortality (15%-30%). Current guidelines recommend these patients are best managed in a multidisciplinary team setting. This study reports experience in the management of SAP within the UK's first reported hub-and-spoke pancreatitis network.

Endoscopic transmural drainage is associated with improved outcomes in disconnected pancreatic duct syndrome: a systematic review and meta-analysis.

Background: Disconnected pancreatic duct syndrome (DPDS) is a complication of acute necrotizing pancreatitis in the neck and body of the pancreas often manifesting as persistent pancreatic fluid collection (PFC) or external pancreatic fistula (EPF). This systematic review and pairwise meta-analysis aimed to review the definitions, clinical presentation, intervention, and outcomes for DPDS.

Methods: The PubMed, EMBASE, MEDLINE, and SCOPUS databases were systematically searched until February 2020 using the PRISMA framework.

Impact of pancreatic enzyme replacement therapy on short- and long-term outcomes in advanced pancreatic cancer: meta-analysis of randomized controlled trials.

: We analyzed randomized controlled trials (RCTs) to assess the impact of PERT on weight change, quality of life, and overall survival (OS) in patients with advanced pancreatic cancer (APC).: All RCTs indexed in PubMed, Medline and Scopus, databases reporting PEI in APC and the effect of PERT were included up to August 2020. The primary outcome measure was OS and the secondary outcome measures were weight change and quality of life.

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).

Meta-analysis of survival outcomes following surgical and non surgical treatments for colorectal cancer metastasis to the lung.

Background: Controversy exists regarding the optimal management of colorectal lung metastases (CRLM). This meta-analysis compared surgical (Surg) versus interventional (chemotherapy and/or radiotherapy) and observational non-surgical (NSurg) management of CRLM.

Methods: A systematic review of the major databases including Medline, Embase, SCOPUS and the Cochrane library was performed.

Meta-Analysis and Meta-Regression of Risk Factors for Surgical Site Infections in Hepatic and Pancreatic Resection.

Background: The risk factors for surgical site infection (SSI) after HPB surgery are poorly defined. This meta-analysis aimed to quantify the SSI rates and risk factors for SSI after pancreas and liver resection.

Methods: The PUBMED, MEDLINE and EMBASE databases were systematically searched using the PRISMA framework.

A Network Meta-analysis of Surgery for Chronic Pancreatitis: Impact on Pain and Quality of Life.

Background: The surgical operation associated with improved pain and quality of life (QoL) in patients with chronic pancreatitis (CP) is unknown.

Method: The Scopus, EMBASE, Medline and Cochrane databases were systematically searched until May 2019, and all randomised trials (RCTs) comparing surgical operations for CP pain were included in a network meta-analysis (NMA).

Results: Four surgical operations for treating CP were directly compared in eight RCTs including 597 patients.

Recurrence Patterns for Pancreatic Ductal Adenocarcinoma after Upfront Resection Versus Resection Following Neoadjuvant Therapy: A Comprehensive Meta-Analysis.

Background: Neoadjuvant therapy (NAT) represents a paradigm shift in the management of patients with pancreatic ductal adenocarcinoma (PDAC) with perceived benefits including a higher R0 rate. However, it is unclear whether NAT affects the sites and patterns of recurrence after surgery. This review seeks to compare sites and patterns of recurrence after resection between patients undergoing upfront surgery (US) or after NAT.

Haemostatic Efficacy of Topical Agents During Liver Resection: A Network Meta-Analysis of Randomised Trials.

Background: Hepatic resection carries a high risk of parenchymal bleeding both intra- and post-operatively. Topical haemostatic agents are frequently used to control bleeding during hepatectomy, with multiple products currently available. However, it remains unknown which of these is most effective for achieving haemostasis and improving peri-operative outcomes.

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.

Critical appraisal of the techniques of pancreatic anastomosis following pancreaticoduodenectomy: A network meta-analysis.

Background: Postoperative pancreatic fistula (POPF) remains a major cause of morbidity following pancreaticoduodenectomy (PD). This network meta-analysis (NMA) compared techniques of pancreatic anastomosis following PD to determine the technique with the best outcome profile.

Methods: A systematic literature search was performed on the Scopus, EMBASE, Medline and Cochrane databases to identify RCTs employing the international study group of pancreatic fistula (ISGPF) definition of POPF.

A systematic review and network meta-analysis of parenchymal transection techniques during hepatectomy: an appraisal of current randomised controlled trials.

Background: Major liver resection can lead to significant morbidity and mortality. Blood loss is one of the most important factors predicting a good outcome. Although various transection methods have been reported, there is no consensus on the best technique.

The association of pregnane X receptor activation with outcomes after liver transplantation-A retrospective study.

Background: Many complications following liver transplantation are linked to ischemia-reperfusion injury. Activation of the pregnane X receptor (PXR) has been shown to alleviate this process in animal models. The aim of this retrospective study was to investigate the effect of early activation of human PXR (hPXR) on postoperative complications and survival following liver transplantation.