Summary
Background
Primary biliary cholangitis (PBC) is an autoimmune hepatobiliary disorder characterized by destruction of liver bile ducts leading to intrahepatic cholestasis. It causes intractable pruritus for which ultraviolet (UV)B phototherapy is an experimental treatment when alternative therapies fail. The pathophysiology of cholestatic itch and the mechanism of action of narrowband UVB in this condition remains poorly understood.
Objectives
To summarize the current literature and propose testable hypotheses for the mechanism of action of phototherapy in attenuating itch.
Methods
A focused PubMed search for articles relating to the pathogenesis of itch in cholestatic disease was performed. A total of 3855 articles were screened and 50 were found suitable for literature review. Evidence from this literature review was combined with author expertise in the area.
Results
Formulated hypotheses focus on the role of bile salts, autotaxin and specific receptors including G‐protein‐coupled bile acid receptor, Gpbar1 (also known as TGR5) and the nuclear transcription factor farnesoid X receptor.
Conclusions
Several testable mechanisms through which phototherapy may exert its effects are discussed in this review. The next steps are to carry out an objective assessment of the efficacy of phototherapy in cholestatic pruritus, gain further knowledge on the underlying pathways, and subsequently trial its use against current licensed therapies. Such studies could lead to increased mechanistic understanding, identification of novel therapeutic targets and the potential to refine phototherapy protocols, leading to improved control of itch and quality of life in patients with PBC.
What's already known about this topic?
Primary biliary cholangitis (PBC) is frequently associated with intractable pruritus for which current treatment options are often unsuccessful.
Phototherapy is used as an experimental treatment for PBC‐associated pruritus when alternative better‐studied treatments fail.
What does this study add?
This study reviews the current literature on the pathophysiology and management of cholestatic pruritus, an area which remains poorly understood.
We propose testable hypotheses of the mechanisms behind the attenuation of cholestatic pruritus with phototherapy.
REQUITE consortium, Development and optimisation of a machine-learning prediction model for acute desquamation following breast radiotherapy in the multi-centre REQUITE cohort, Advances in Radiation Oncology (2022), doi:
Aims
Anal cancer is primarily treated using concurrent chemoradiotherapy (CRT), with conformal techniques such as intensity modulated radiotherapy (IMRT) and volumetric arc therapy (VMAT) now being the standard techniques utilised across the world. Despite this, there is still very limited consensus on prognostic factors for outcome following conformal CRT. This systematic review aims to evaluate the existing literature to identify prognostic factors for a variety of oncological outcomes in anal cancer, focusing on patients treated with curative intent using contemporary conformal radiotherapy techniques.
Materials and methods
A literature search was conducted using Medline and Embase to identify studies reporting on prognostic factors for survival and cancer-related outcomes after conformal CRT for anal cancer. The prognostic factors which were identified as significant in univariable and multivariable analysis, along with their respective factor effects (where available) were extracted. Only factors reported as prognostic in more than one study were included in the final results.
Results
The results from 19 studies were analysed. In both univariable and multivariable analysis, N stage, T stage, and sex were found to be the most prevalent and reliable clinical prognostic factors for the majority of outcomes explored. Only a few biomarkers have been identified as prognostic by more than one study – pre-treatment biopsy HPV load, as well as the presence of leukocytosis, neutrophilia and anaemia at baseline measurement. The results also highlight the lack of studies with large cohorts exploring the prognostic significance of imaging factors.
Conclusion
Establishing a set of prognostic and potentially predictive factors for anal cancer outcomes can guide the risk stratification of patients, aiding the design of future clinical trials. Such trials will in turn provide us with greater insight into how to effectively treat this disease using a more personalised approach.
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