The Management and Outcomes of Patients with Extra-Pulmonary Neuroendocrine Neoplasms and Brain Metastases.

Background: Brain metastases (BMs) in patients with extra-pulmonary neuroendocrine neoplasms (EP-NENs) are rare, and limited clinical information is available. The aim of this study was to detail the clinicopathological features, management and outcomes in patients with EP-NENs who developed BMs.

Methods: A retrospective single-centre analysis of consecutive patients with EP-NENs (August 2004-February 2020) was conducted.

Use of the Rockwood Clinical Frailty Scale in patients with advanced hepatopancreaticobiliary malignancies.

Background: Co-existing frailty in older patients with hepatopancreaticobiliary (HPB) malignancies is common. This study assessed the relationship between the Rockwood Clinical Frailty scale (CFS) and systemic anti-cancer therapy dose intensity (SACT-DI) and overall survival (OS) in patients with advanced HPB malignancies.

Research Design And Methods: CFS was assessed prospectively for consecutive patients with newly diagnosed advanced HPB malignancy (The Christie; Sep-2019 to June-2020).

Molecular Profiling of Well-Differentiated Neuroendocrine Tumours: The Role of ctDNA in Real-World Practice.

: The role of tumour genomic profiling in the clinical management of well-differentiated neuroendocrine tumours (WdNETs) is unclear. Circulating tumour DNA (ctDNA) may be a useful surrogate for tumour tissue when the latter is insufficient for analysis. : Patients diagnosed with WdNETs underwent ctDNA genomic profiling (FoundationLiquid); non-WdNETs (paraganglioma, goblet cell or poorly-differentiated neuroendocrine carcinoma) were used for comparison.

Findability of UK health datasets available for research: a mixed methods study.

Objective: How health researchers find secondary data to analyse is unclear. We sought to describe the approaches that UK organisations take to help researchers find data and to assess the findability of health data that are available for research.

Methods: We surveyed established organisations about how they make data findable.

Prospective observational study of prevalence, assessment and treatment of pancreatic exocrine insufficiency in patients with inoperable pancreatic malignancy (PANcreatic cancer Dietary Assessment (PanDA): a study protocol.

Introduction: Pancreatic exocrine insufficiency (PEI) in patients with pancreatic malignancy is well documented in the literature and is known to negatively impact on overall survival and quality of life. A lack of consensus opinion remains on the optimal diagnostic test that can be adapted for use in a clinical setting for this cohort of patients. This study aims to better understand the prevalence of PEI and the most suitable diagnostic techniques in patients with advanced pancreatic malignancy.

Molecular Profiling in Daily Clinical Practice: Practicalities in Advanced Cholangiocarcinoma and Other Biliary Tract Cancers.

Background: Molecular profiling is becoming increasingly relevant in the management of patients with advanced cancer; to identify targetable aberrations and prognostic markers to enable a precision medicine strategy.

Methods: Eligible patients were those diagnosed with advanced biliary tract cancer (BTC) including intrahepatic (iCCA) and extrahepatic cholangiocarcinoma (eCCA), gallbladder cancer (GBC), and ampullary carcinoma (Amp) who underwent molecular profiling between April 2017 and June 2020 based on analysis of either tumour samples (FoundationOne CDx/Oncomine platforms) or ctDNA (FoundationOne Liquid platform (Foundation Medicine, Cambridge, MA, USA)). Baseline patient characteristics and molecular profiling outcomes were extracted.

NUC-1031, use of ProTide technology to circumvent gemcitabine resistance: current status in clinical trials.

Background: Resistance to gemcitabine chemotherapy is common in patients with pancreatic ductal adenocarcinoma (PDAC), biliary tract cancer (BTC) and ovarian cancers (OC), conferring poor survival. Use of ProTide technology led to the development of a 'partially-activated' monophosphorylated gemcitabine compound, termed NUC-1031. NUC-1031 enters cancer cells independent of the human equilibrative nucleoside transporter, does not require deoxycytidine kinase-mediated activation and resists cytidine deaminase-mediated breakdown into toxic by-products.

Systemic therapies in advanced hepatocellular carcinoma: How do older patients fare?

Advanced hepatocellular cancer (HCC) is the fourth leading cause of cancer-related death globally and is most common in elderly patients with a peak incidence in the UK at ages 85-89 years. In addition to the well-established risk factors of alcohol and viral hepatitis B and C, rising obesity and associated non-alcoholic fatty liver disease is projected to contribute to increased incidence of advanced HCC in elderly patients. The management of advanced HCC is changing rapidly; for over a decade the multi-kinase inhibitor sorafenib has been the only treatment option that offered a proven survival advantage, but in the last 4 years other treatment options have emerged including other kinase inhibitors, and monoclonal antibodies targeting angiogenesis and immune checkpoint inhibitors.

Outcomes in older patients with biliary tract cancer.

The majority of patients diagnosed with cancer are ≥65 years. However, inclusion of older patients with cancer in clinical trials is limited, and so there is less evidence to guide systemic therapeutic decisions in these patients. There is also debate surrounding the definition of "older patients".

CCR7 selected gene-modified T cells maintain a central memory phenotype and display enhanced persistence in peripheral blood in vivo.

Background: Adoptive T cell immunotherapy (ATCT) for cancer entails infusing patients with T cells that recognise and destroy tumour cells. Efficient engraftment of T cells and persistence in the circulation correlate with favourable clinical outcomes. T cells of early differentiation possess an increased capacity for proliferation and therefore persistence, using these cells for ATCT could therefore lead to improved clinical outcomes.

Chemoradiotherapy for squamous cell anal carcinoma: a review of prognostic factors.

Aim: Previous literature has sought prognostic factors for the survival of anal cancer patients. The present study aimed to determine prognostic factors for local disease recurrence, distant metastasis and survival for patients treated with radical chemoradiotherapy (CRT) at the Rosemere Cancer Centre, Preston, UK.

Method: Patients treated with CRT for nonmetastatic squamous cell anal cancer between September 2000 and January 2013 were studied.

Cartilage repair using human embryonic stem cell-derived chondroprogenitors.

In initial work, we developed a 14-day culture protocol under potential GMP, chemically defined conditions to generate chondroprogenitors from human embryonic stem cells (hESCs). The present study was undertaken to investigate the cartilage repair capacity of these cells. The chondrogenic protocol was optimized and validated with gene expression profiling.

Synthesis of embryonic tendon-like tissue by human marrow stromal/mesenchymal stem cells requires a three-dimensional environment and transforming growth factor β3.

Tendon-like tissue generated from stem cells in vitro has the potential to replace tendons and ligaments lost through injury and disease. However, thus far, no information has been available on the mechanism of tendon formation in vitro and how to accelerate the process. We show here that human mesenchymal stem cells (MSCs) and bone marrow-derived mononuclear cells (BM-MNCs) can generate tendon-like tissue in 7days mediated by transforming growth factor (TGF) β3.

An experimental model for studying the biomechanics of embryonic tendon: Evidence that the development of mechanical properties depends on the actinomyosin machinery.

Tendons attach muscles to bone and thereby transmit tensile forces during joint movement. However, a detailed understanding of the mechanisms that establish the mechanical properties of tendon has remained elusive because of the practical difficulties of studying tissue mechanics in vivo. Here we have performed a study of tendon-like constructs made by culturing embryonic tendon cells in fixed-length fibrin gels.

The cellular biology of flexor tendon adhesion formation: an old problem in a new paradigm.

Intrasynovial flexor tendon injuries of the hand can frequently be complicated by tendon adhesions to the surrounding sheath, limiting finger function. We have developed a new tendon injury model in the mouse to investigate the three-dimensional cellular biology of intrasynovial flexor tendon healing and adhesion formation. We investigated the cell biology using markers for inflammation, proliferation, collagen synthesis, apoptosis, and vascularization/myofibroblasts.

Tension is required for fibripositor formation.

Embryonic tendon cells (ETCs) have actin-rich fibripositors that accompany parallel bundles of collagen fibrils in the extracellular matrix. To study fibripositor function, we have developed a three-dimensional cell culture system that promotes and maintains fibripositors. We show that ETCs cultured in fixed-length fibrin gels replace the fibrin during ~6 days in culture with parallel bundles of narrow-diameter collagen fibrils that are uniaxially aligned with fibripositors, thereby generating a tendon-like construct.

Characterization of soluble glycoprotein D-mediated herpes simplex virus type 1 infection.

Herpes simplex virus type 1 (HSV-1) entry into permissive cells involves attachment to cell-surface glycosaminoglycans (GAGs) and fusion of the virus envelope with the cell membrane triggered by the binding of glycoprotein D (gD) to cognate receptors. In this study, we characterized the observation that soluble forms of the gD ectodomain (sgD) can mediate entry of gD-deficient HSV-1. We examined the efficiency and receptor specificity of this activity and used sequential incubation protocols to determine the order and stability of the initial interactions required for entry.