Patients Undergoing Systemic Anti-Cancer Therapy Who Require Surgical Intervention: What Surgeons Need to Know.

As part of routine cancer care, patients may undergo elective surgery with the aim of long-term cure. Some of these patients will receive systemic anti-cancer therapy (SACT) in the neoadjuvant and adjuvant settings. The majority of patients, usually with locally advanced or metastatic disease, will receive SACT with palliative intent. These treatment options are expanding beyond traditional chemotherapy to include targeted therapies, immunotherapy, hormone therapy, radionuclide therapy and gene therapy. During treatment, some patients will require surgical intervention on an urgent or emergency basis. This narrative review examined the evidence base for SACT-associated surgical risk and the precautions that a surgical team should consider in patients undergoing SACT.

Future therapeutic strategies in the treatment of extrapulmonary neuroendocrine carcinoma: a review.

Neuroendocrine neoplasms (NENs) are rare malignancies arising most commonly in the gastrointestinal and bronchopulmonary systems. Neuroendocrine carcinomas (NECs) are a subgroup of NENs characterised by aggressive tumour biology, poor differentiation and dismal prognosis. Most NEC primary lesions arise in the pulmonary system. However, a small proportion arise outside of the lung and are termed extrapulmonary (EP)-, poorly differentiated (PD)-NECs. Patients with local or locoregional disease may benefit from surgical excision; however, this is often not an option, due to late presentation. To date, treatment has mirrored that of small-cell lung cancer, with platinum-etoposide forming the basis of first-line treatment. There is a lack of consensus in relation to the most effective second-line treatment option. Low incidence, an absence of representative preclinical models and a lack of understanding of the tumour microenvironment all present challenges to drug development in this disease group. However, progress made in elucidating the mutational landscape of EP-PD-NEC and the observations made in several clinical trials are paving the way towards improving outcomes for these patients. The optimisation and strategic delivery of chemotherapeutic interventions according to tumour characteristics and the utilisation of targeted and immune therapies in clinical studies have yielded mixed results. Targeted therapies that complement specific genetic aberrations are under investigation, including AURKA inhibitors in those with MYCN amplifications, BRAF inhibitors in those with BRAFV600E mutations and EGFR suppression, and Ataxia Telangiectasia and Rad3-related inhibitors in patients with ATM mutations. Immune checkpoint inhibitors (ICIs) have conferred promising results in several clinical trials, particularly with dual ICIs and in combination with targeted therapy or chemotherapy. However, further prospective investigations are required to elucidate the impact of programmed cell death ligand 1 expression, tumour mutational burden and microsatellite instability on response. This review aims to explore the most recent developments in the treatment of EP-PD-NEC and contribute towards the requirement for clinical guidance founded on prospective evidence.

Monitoring the Disassembly of Virus-like Particles by 19F-NMR.

Virus-like particles (VLPs) are stable protein cages derived from virus coats. They have been used extensively as biomolecular platforms, e.g., nanocarriers or vaccines, but a convenient in situ technique is lacking for tracking functional status. Here, we present a simple way to monitor disassembly of 19F-labeled VLPs derived from bacteriophage Qß by 19F NMR. Analysis of resonances, under a range of conditions, allowed determination not only of the particle as fully assembled but also as disassembled, as well as detection of a degraded state upon digestion by cells. This in turn allowed mutational redesign of disassembly and testing in both bacterial and mammalian systems as a strategy for the creation of putative, targeted-VLP delivery systems.

Local entropy and structure in a two-dimensional frustrated system.

We calculate the local contributions to the Shannon entropy and excess entropy and use these information theoretic measures as quantitative probes of the order arising from quenched disorder in the diluted Ising antiferromagnet on a triangular lattice. When one sublattice is sufficiently diluted, the system undergoes a temperature-driven phase transition, with the other two sublattices developing magnetizations of equal magnitude and opposite sign as the system is cooled.(1) The diluted sublattice has no net magnetization but exhibits spin glass ordering. The distribution of local entropies shows a dramatic broadening at low temperatures; this indicates that the system's total entropy is not shared equally across the lattice. The entropy contributions from some regions exhibit local reentrance, although the entropy of the system decreases monotonically as expected. The average excess entropy shows a sharp peak at the critical temperature, showing that the excess entropy is sensitive to the structural changes that occur as a result of the spin glass ordering.