Miller RE, et al. J Gynecol Oncol. 2022 Mar;33:e44. https://doi.org/10.3802/jgo.2022.33.e44

Poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitors have revolutionised the management of patients with high-grade serous and endometrioid ovarian cancer demonstrating significant improvements in progression-free survival. Whilst the greatest benefit is seen with BRCA1/2 mutant cancers, it is clear that the benefit extends beyond this group. This sensitivity is thought to be due to homologous recombination deficiency (HRD), which is present in up to 50% of the high-grade serous cancers. Several different HRD assays exist, which fall into one of three main categories: homologous recombination repair (HRR)-related gene analysis, genomic “scars” and/or mutational signatures, and real-time HRD functional assessment. We review the emerging data on HRD as a predictive biomarker for PARP inhibitors and discuss the merits and disadvantages of different HRD assays.

Pancreatic ductal adenocarcinoma (PDAC) treatments have historically focused on targeting tumor cells directly. However, in pancreatic masses, the stroma encasing the malignant epithelial cells constitutes up to 80% to 90% of the tumor bulk. This extracellular matrix, which was previously neglected when designing cancer therapies, is now considered fundamental for tumor progression and drug delivery. Desmoplastic tissue is extensively cross-linked, resulting in tremendous tensile strength. This key pathological feature is procarcinogenic, linking PDAC and breast cancer (BC). Physical forces exerted onto cellular surfaces are detected intracellularly and transduced via biochemical messengers in a process called mechanotransduction. Mechanotransduction and tensional homeostasis are linked, with an integral role in influencing tumor growth, metastasis, and interactions with the immune system. It is essential to enhance our knowledge of these integral elements of parenchymal tumors. We aim to review the topic, with a special emphasis on desmoplastic processes and their importance in pancreatic and BC development and treatments, mindful that innovative diagnostic and therapeutic strategies cannot focus on biochemical pathways alone. We then focus on common therapeutic targets identified in both PDAC and BC models and/or patients, aiming to understand these treatments and draw similarities between the two tumors.

Summary: In response to our current global pandemic, unprecedented healthcare changes may have significant consequences for cancer patients in the United Kingdom. We explore why cancer patients may be more susceptible to severe infection and complications, highlighting various interventions that may help to ensure continuity of care in this unique cohort.

Summary: Background: Early coronavirus disease 2019 (COVID-19) diagnosis prior to laboratory testing results is crucial for infection control in hospitals. Models exist predicting COVID-19 diagnosis, but significant concerns exist regarding methodology and generalizability. Aim: To generate the first COVID-19 diagnosis risk score for use at the time of hospital admission using the TRIPOD (transparent reporting of a multivariable prediction model for individual prognosis or diagnosis) checklist. Design: A multivariable diagnostic prediction model for COVID-19 using the TRIPOD checklist applied to a large single-centre retrospective observational study of patients with suspected COVID-19. Methods: 581 individuals were admitted with suspected COVID-19; the majority had laboratory-confirmed COVID-19 (420/581, 72.2%). Retrospective collection was performed of electronic clinical records and pathology data. Results: The final multivariable model demonstrated AUC 0.8535 (95% confidence interval 0.8121–0.8950). The final model used six clinical variables that are routinely available in most low and high-resource settings. Using a cut-off of 2, the derived risk score has a sensitivity of 78.1% and specificity of 86.8%. At COVID-19 prevalence of 10% the model has a negative predictive value (NPV) of 96.5%. Conclusions: Our risk score is intended for diagnosis of COVID-19 in individuals admitted to hospital with suspected COVID-19. The score is the first developed for COVID-19 diagnosis using the TRIPOD checklist. It may be effective as a tool to rule out COVID-19 and function at different pandemic phases of variable COVID-19 prevalence. The simple score could be used by any healthcare worker to support hospital infection control prior to laboratory testing results.

As our population ages, the demand for surgical services in older people is increasing exponentially. Shown to be indispensable in the care of medical patients, use of the comprehensive geriatric assessment (CGA) is also growing in the perioperative setting. We present the case of a previously independent 82-year-old man who underwent a standard preoperative assessment and surgical aortic valve replacement. In the 7 months that followed, prior to his death, he suffered a rapid functional decline contributed to by slow postoperative recovery, delirium and recurrent falls. Post-mortem revealed cardiac amyloid deposition and extensive small vessel disease in the brain. This case highlights the importance of the CGA in the perioperative management of older patients, especially in identification and optimisation of geriatric syndromes and consideration of less-invasive alternative treatments. We review the existing literature on CGA use in cardiothoracic and vascular surgical settings, drawing on experiences learnt from the above case.