Orthopaedic surgery in the palliation of cancer

Metastatic spread of cancer to bone is frequent and causes pain, disability, and functional limitation. Non-surgical treatments such as chemotherapy and hormone therapy are effective in early disease. Administration of bisphosphonates or osteoprotegerin inhibitors prevent new ‘bone events’, thereby avoiding pain, radiation, and surgery. Radiotherapy arrests disease and relieves pain in many cases. Surgery is needed when the bone is weak or fractured. It effectively relieves pain and preserves function by bypassing the deficient bone with site-specific reconstructive surgery. Surgery should be selected based on projections of patient survival. New tools to make these projections are now available (https://www.pathfx.org/). New targeted drug therapies appear to be changing metastatic bone disease into a more chronic condition. This will alter the management of local disease in many histological subtypes of metastatic cancers.

Pustular Psoriasis and Associated Musculoskeletal Disorders

Pustular psoriasis (PsO) is an uncommon variant of PsO that may present in a generalized or localized fashion with or without musculoskeletal or systemic inflammatory involvement. Generalized pustular PsO (GPP) presents as a widespread acute or subacute pustular eruption that may be familial and is often associated with severe flares and systemic inflammation. The palmoplantar pustulosis variant is localized to palms and soles, whereas acrodermatitis continua of Hallopeau is localized to the nail apparatus. Patients with pustular PsO may have overlapping plaque PsO and may develop psoriatic arthritis (PsA). Pustulosis is also a feature of both synovitis, acne, pustulosis, hyperostosis, osteomyelitis (SAPHO) syndrome and chronic nonbacterial osteomyelitis. At the 2020 Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) annual meeting, members were given an overview of the cutaneous features of pustular PsO, SAPHO, and recent insights into the genetics of GPP, leading to new targeted drug therapies and the development of validated endpoints.

Psychiatric Toxicities of Cancer Therapies

The psychiatric effects of cancer treatments should receive renewed interest based on cancer treatment–related paradigm shifts and the ever-changing parade of new and improving cancer treatments. Precision medicine in oncology relies on personal molecular analysis and is touching patients in profound ways by providing prognostic information to guide treatment decisions. Due to enhancements in molecular sciences as well as data collection and management, the development of new treatments has accelerated in the field of oncology in particular. While there are many advantages to increasing the speed of drug development, ensuring that the psychiatric and psychological outcomes of these treatments are well understood remains a largely undeveloped area. This chapter introduces immunotherapies and targeted drug therapies, their mechanisms of action, and what is known about their psychiatric toxicity profiles. The chapter focuses on outlining the scientific rationale behind newer treatments such as immunotherapy and targeted therapies so that psychiatric consequences, perhaps yet to be discovered, may be further understood. Increased attention to patient-reported outcomes will hopefully enhance the identification of psychiatric consequences of immunotherapy and targeted therapies in oncology.

Genetic and Epigenetic Modulation of Drug Resistance in Cancer: Challenges and Opportunities

Cancer is a complex disease that has the ability to develop resistance to traditional therapies. The current chemotherapeutic treatment has become increasingly sophisticated, yet it is not 100% effective against disseminated tumours. Anticancer drugs resistance is an intricate process that ascends from modifications in the drug targets suggesting the need for better targeted therapies in the therapeutic arsenal. Advances in the modern techniques such as DNA microarray, proteomics along with the development of newer targeted drug therapies might provide better strategies to overcome drug resistance. This drug resistance in tumours can be attributed to an individual’s genetic differences, especially in tumoral somatic cells but acquired drug resistance is due to different mechanisms, such as cell death inhibition (apoptosis suppression) altered expression of drug transporters, alteration in drug metabolism epigenetic and drug targets, enhancing DNA repair and gene amplification. This review also focusses on the epigenetic modifications and microRNAs, which induce drug resistance and contributes to the formation of tumour progenitor cells that are not destroyed by conventional cancer therapies. Lastly, this review highlights different means to prevent the formation of drug resistant tumours and provides future directions for better treatment of these resistant tumours.