Richard Skipworth

• University of Edinburgh

Purpose of review Cancer cachexia (CC) is a paraneoplastic syndrome (PNS) that is characterised by anorexia, weight loss, fatigue and reduced function. This review explores the molecular drivers of CC and other PNS, identifying shared pathways and highlighting unexplored gaps in research. Recent findings Recent studies have provided further eviden...

Background Cachexia is common in oesophagogastric cancer, yet heterogeneity in its definition has hindered clinical utilisation. This study compared the two established cachexia definitions (Fearon’s consensus definition and the Global Leadership Initiative on Malnutrition [GLIM] criteria) and their relationship with survival amongst patients with...

Background In patients receiving anti‐cancer treatment, cachexia results in poorer oncological outcomes. However, there is limited understanding and no systematic review of oncological endpoints in cancer cachexia (CC) trials. This review examines oncological endpoints in CC clinical trials. Methods An electronic literature search of MEDLINE, Emba...

Background Cancer cachexia presents a significant challenge, but the ghrelin agonist anamorelin shows promise as a potential treatment. This study examined whether the baseline systemic inflammatory response (SIR) (measured by the modified Glasgow Prognostic Score [mGPS]), low BMI or greater weight loss, was associated with a differential treatment...

Remote monitoring is essential for healthcare digital transformation, however, this poses greater burdens on healthcare providers to review and respond as the data collected expands. This study developed a multimodal neural network to automate assessments of patient-generated data from remote postoperative wound monitoring. Two interventional studi...

Background: Cachexia is common in patients with oesophagogastric cancer. The syndrome is characterised by tissue wasting (muscle and fat), anorexia, and reduced physical function, which result from complex interactions between the tumour and its host. Heterogeneity in the diagnostic criteria used for cachexia has hindered their clinical utilisation...

Background Single‐slice computed tomography (CT) body composition has been studied extensively for prognostication in patients with cancer. New software packages can also provide multi‐slice volumetric measurements, but the clinical utility of these remains under explored. This study aimed to evaluate the agreement between single‐ and multi‐slice b...

Objective To review and synthesise research on technological debiasing strategies across domains, present a novel distributed cognition-based classification system, and discuss theoretical implications for the field. Background Distributed cognition theory is valuable for understanding and mitigating cognitive biases in high-stakes settings where...

Background Prehabilitation is safe, feasible and may improve a range of outcomes in patients with oesophago-gastric cancer (OGC). Recent studies have suggested the potential of prehabilitation to improve body composition, sarcopenia and physical fitness, reduce surgical complications and improve quality of life. Despite this, prehabilitation servic...

Background There is increasing availability of operative video for use in surgical training. Emerging technologies can now assess video footage and automatically generate metrics that could be harnessed to improve the assessment of operative performance. However, a comprehensive understanding of which technology features are most impactful in surgi...

Aims There is an increasing availability of operative video for use in surgical training. Emerging technologies can now assess video footage and automatically generate metrics that could be harnessed to improve the assessment of operative performance. This scoping review explores the current application of automated video analytics in surgical trai...

Aim Classifications for cancer cachexia remain heterogenous within the existing literature. The aim of this study is to compare prognostication using three established descriptors: the Fearon et al. consensus definition, Martin et al.’s weight loss grading system and the Global Leadership Initiative on Malnutrition (GLIM) criteria, in patients with...

Aim The Global Leadership Initiative on Malnutrition (GLIM) consensus proposed that patients should meet one of three phenotypic criteria for a diagnosis of malnutrition. This study examined the association between these criteria and survival in oesophagogastric cancer. Methods Consecutive patients newly diagnosed with oesophagogastric cancer were...

Background Features of cancer cachexia are known to adversely influence patient outcomes, yet few currently inform clinical decision-making. This study assessed the value of ‘cachexia index’ (CXI), a novel prognostic marker, in patients planned for curative multimodal therapy (neoadjuvant chemotherapy (NAC) and surgery) for oesophagogastric cancer....

Background Cancer cachexia is highly prevalent in oesophagogastric cancer, particularly amongst patients with advanced stage disease. However, classifications for cachexia remain heterogenous within the existing literature. The aim of this study is to compare prognostication using the Fearon et al. consensus definition to the Global Leadership Init...

Background Single-slice computed tomography (CT) body composition has been studied extensively for prognostication in patients with cancer. New software packages can also provide multi-slice volumetric measurements, but the clinical utility of these remains under explored. This study aimed to evaluate the concordance between single- and multi-slice...

Introduction The efficiency of multidisciplinary teams (MDTs) in cancer care hinges on facilitating clinicians’ cognitive processes as they navigate complex and uncertain judgements during treatment planning. When systems and workflows are not designed to adequately support human judgement and decision-making, even experts are prone to fallible rea...

Background The reporting of randomised controlled non-inferiority (NI) drug trials is poor with less than 50% of published trials reporting a justification of the NI margin. This is despite the introduction of the Consolidated Standards of Reporting Trials (CONSORT) extension on reporting of NI and equivalence in randomised trials. It is critical t...

Background: CT-derived measures of body composition have been shown to have prognostic value in patients with cancer. However, few studies have compared these observations across tumor types and stages of disease. The aim of the present study was to compare body composition measures between two types of cancers, i.e. colorectal cancer (CRC), which...

Purpose of review The following article examines the rationale for an inflammation-first approach for diagnosing cachexia and how the current Global Leadership Initiative on Malnutrition (GLIM) framework may be adapted to facilitate this. Recent findings Recently, the GLIM have published guidance on the measurement of inflammation in the context o...

Regulatory agencies require evidence that endpoints correlate with clinical benefit before they can be used to approve drugs. Biomarkers are often considered surrogate endpoints. In cancer cachexia trials, the measurement of biomarkers features frequently. The aim of this systematic review was to assess the frequency and diversity of biomarker endp...

Purpose of review Cachexia is a devasting syndrome which impacts a large number of patients with cancer. This review aims to provide a comprehensive overview of the central mechanisms of cancer cachexia. In particular, it focuses on the role of the central nervous system (CNS), the melanocortin system, circulating hormones and molecules which are p...

Esophageal adenocarcinoma is a prominent example of cancer characterized by frequent amplifications in oncogenes. However, the mechanisms leading to amplicons that involve breakage-fusion-bridge cycles and extrachromosomal DNA are poorly understood. Here, we use 710 esophageal adenocarcinoma cases with matched samples and patient-derived organoids...

Significant variation exists in the outcomes used in cancer cachexia trials, including measures of body composition, which are often selected as primary or secondary endpoints. To date, there has been no review of the most commonly selected measures or their potential sensitivity to detect changes resulting from the interventions being examined. Th...

Palliative care has evolved rapidly in recent years. Not only is the field dealing with an increasingly elderly and multi-morbid population, it is also addressing a wider variety of complex diagnoses such as heart failure, renal failure, advanced lung disease, frailty, and dementia. As part of our Challenging Cases series, the cases in this book no...

Background Cancer cachexia is characterized by severe loss of muscle and fat involving a complex interplay of host–tumour interactions. While much emphasis has been placed on understanding the molecular mechanisms associated with cachexia, understanding the heritable component of cachexia remains less explored. The current study aims to identify co...

Background Oesophageal cancer, in particular adenocarcinoma, has a strong male predominance. However, the impact of patient sex on operative and oncologic outcomes and recovery of health-related quality of life is poorly documented, and was the focus of this large multicentre cohort study. Methods All consecutive patients who underwent oncological...

Background Features of cancer cachexia adversely influence patient outcomes, yet few currently inform clinical decision-making. This study assessed the value of the cachexia index (CXI), a novel prognostic marker, in patients for whom neoadjuvant chemotherapy and surgery for oesophagogastric cancer is planned. Methods Consecutive patients newly di...

Introduction: Boerhaave syndrome is a rare clinical entity associated with high rates of morbidity and mortality. Early recognition of the symptoms, and identification of the site and extension of the injury are key in improving the prognosis. Methods: This study presents data on the mortality, morbidity and length of hospital stay in patients d...

The use of patient‐reported outcomes (PROMs) of quality of life (QOL) is common in cachexia trials. Patients' self‐report on health, functioning, wellbeing, and perceptions of care, represent important measures of efficacy. This review describes the frequency, variety, and reporting of QOL endpoints used in cancer cachexia clinical trials. Electron...

Background Personalising management of primary oesophageal adenocarcinoma requires better risk stratification. Lack of independent validation of proposed imaging biomarkers has hampered clinical translation. We aimed to prospectively validate previously identified prognostic grey-level co-occurrence matrix (GLCM) CT features for 3-year overall surv...

Background Intelectin-1 (ITLN1) is an adipokine with multiple physiological functions, including a role in tumour formation and development. Previous research reported variable ITLN1 levels for cancer patients and healthy individuals. This study aimed to compare ITLN1 concentrations between controls and cancer patients and to determine the adipokin...

There is no consensus on the optimal endpoint(s) in cancer cachexia trials. Endpoint variation is an obstacle when comparing interventions and their clinical value. The aim of this systematic review was to summarize and evaluate endpoints used to assess appetite and dietary intake in cancer cachexia clinical trials. A search for studies published f...

In cancer cachexia trials, measures of physical function are commonly used as endpoints. For drug trials to obtain regulatory approval, efficacy in physical function endpoints may be needed alongside other measures. However, it is not clear which physical function endpoints should be used. The aim of this systematic review was to assess the frequen...

Background Over the last twenty years, treatment of oesophageal cancer has changed towards a multimodal approach to achieve better clinical outcomes. Detailed staging paradigms and neoadjuvant treatment have resulted in a longer time period before oesophagectomy, but literature on the prognostic impact of longer waiting times is scarce in this fiel...

Background Cancer cachexia is not purely an end-stage phenomenon and even influences the outcome of patients with potentially curative malignancies. This review aims to examine the effect of pre-treatment cachexia on survival in patients undergoing resection of an oesophagogastric malignancy. Methods A systematic literature search of MEDLINE, EMBA...

Aim Body composition has been used extensively for prognostication across malignant and benign diseases. Systemic inflammation is both a key driver of cancer cachexia and a common finding in patients presenting with acute pathology. However, its influence on body composition is poorly understood. This study aimed to longitudinally assess computed t...

Background: Cancer cachexia is not purely an end-stage phenomenon and can influence the outcomes of patients with potentially curable disease. This review examines the effect of pre-treatment cachexia on overall survival, in patients undergoing surgical resection of oesophagogastric cancer. Methods: A systematic literature search of MEDLINE, EMB...

Cachexia–anorexia cancer syndrome remains an unmet clinical need with a dearth of treatment and no standard of care. Acting through the endocannabinoid system, cannabinoids are one potential cancer cachexia treatment. Herein, the potential mechanisms for cannabinoids for cancer cachexia are discussed as are previous and ongoing clinical trials.

Background Cancer cachexia is characterized by severe loss of muscle and fat involving a complex interplay of host-tumor interactions. While much emphasis has been made in understanding the molecular mechanisms associated with cachexia, understanding the heritable component of cachexia remains less explored. The current study aims to identify Copy...

A variety of mutational processes drive cancer development, but their dynamics across the entire disease spectrum from pre-cancerous to advanced neoplasia are poorly understood. We explore the mutagenic processes shaping oesophageal adenocarcinoma tumorigenesis in 997 instances comprising distinct stages of this malignancy, from Barrett Oesophagus...

Purpose of review: The complexity of the cancer cachexia phenotype has undoubtedly hindered researchers' understanding of this devastating syndrome. The presence and magnitude of host-tumour interactions are rarely considered during clinical decision-making within the current staging paradigm. Furthermore, treatment options for those patients who...

Background: Muscle wasting during cancer cachexia is mediated by protein degradation via autophagy and ubiquitin-linked proteolysis. These processes are sensitive to changes in intracellular pH ([pH]i ) and reactive oxygen species, which in skeletal muscle are partly regulated by histidyl dipeptides, such as carnosine. These dipeptides, synthesize...

Simple Summary Measures of body composition have been used extensively for prognostication across an array of malignant and benign diseases. Systemic inflammation is both a key driver of cancer cachexia and a common finding in patients presenting with acute pathology. However, its influence on estimates of body composition remains poorly understood...

This article highlights the importance of considering Cognitive Load (CL) and Cognitive Load Theory (CLT) during surgical training, focusing on the acquisition of intra-operative skills. It describes the basis of CLT with the overarching aim of describing CLT-based techniques to enhance current training strategies and surgical performance, many of...

Introduction Surgeons need high fidelity, high quality, objective, non-judgemental and quantitative feedback to measure their performance in order to optimise their performance and improve patient safety. This can be provided through surgical sabermetrics, defined as ‘advanced analytics of digitally recorded surgical training and operative procedur...

Introduction: Failure to rescue (FTR) is an important outcome measure after esophagectomy and reflects mortality after postoperative complications. Differences in FTR have been associated with hospital resection volume. However, insight into how centers manage complications and achieve their outcomes is lacking. Anastomotic leak (AL) is a main con...

Anastomotic leak (AL) is a common but severe complication after esophagectomy, and over 10% of patients with AL suffer mortality. Different prognostic factors in patients with AL are known, but a tool to predict mortality after AL is lacking. This study aimed to develop a prediction model for postoperative mortality in patients with AL after esopha...

Opinion statement Considerable advances in the investigation and management of oesophagogastric cancer have occurred over the last few decades. While the historically dismal prognosis associated with these diseases has improved, outcomes remain very poor. Cancer cachexia is an often neglected, yet critical, factor for this patient group. There is a...

Within the cancer population, 50–80% of patients will develop cachexia, impacting negatively on their ability to tolerate or gain benefit from either curative or palliative treatment. To date, although collaborative management guidelines have been developed, there are no internationally standardised management programmes used in the clinical forum...

Skeletal muscle homeostasis is essential for the maintenance of a healthy and active lifestyle. Imbalance in muscle homeostasis has significant consequences such as atrophy, loss of muscle mass, and progressive loss of functions. Aging-related muscle wasting, sarcopenia, and atrophy as a consequence of disease, such as cachexia, reduce the quality...

12110 Background: BW loss and anorexia are key clinical manifestations of cancer cachexia, a multifactorial syndrome affecting around 80% of patients (pts) with advanced cancer. BW loss is associated with reduced tolerance and response to cancer therapy, and shorter survival. ANAM is a novel, oral selective ghrelin receptor agonist. In ROMANA 1 and...

Cancer cachexia has long been perceived as a nutritional syndrome. However, nutritional interventions have continued to be ineffective. With the recent recognition of the importance of systemic inflammation in the definition of this syndrome and treatment, has the time come to consider whether this syndrome is primarily a manifestation of systemic...

Lung cancer is the commonest malignancy worldwide and the leading cause of cancer death. Half of patients with lung cancer present with advanced disease. The number of systemic therapies including immunotherapy and targeted treatment are rapidly increasing. Despite this, the outcomes for many patients with locally advanced and advanced lung cancer...

Oesophageal adenocarcinoma (OAC) provides an ideal case study to characterize large-scale rearrangements. Using whole genome short-read sequencing of 383 cases, for which 214 had matched whole transcriptomes, we observed structural variations (SV) with a predominance of deletions, tandem duplications and inter-chromosome junctions that could be ide...

Background: Advance (anticipatory) care planning (ACP) requires discussions between patients and healthcare professionals about planning for future deterioration in health. ACP improves care coordination but uptake is limited and often deferred. Aim: To assess the feasibility and acceptability to patients, carers, and GPs of a primary care ACP i...

Background Intelectin (ITLN) is an adipokine with two homologs—ITLN1 and ITLN2—that has various physiological functions. Studies analyzing the relationship between ITLN and cancer are focused on ITLN1; the available literature on ITLN2 and cancer is limited. This review aims to evaluate the role of ITLN1 in cancer without imposing any inclusion cri...

Cancer cachexia is an unmet clinical need that affects more than 50% of patients with cancer. The systemic inflammatory response, which is mediated by a network of cytokines, has an established role in the genesis and maintenance of cancer as well as in cachexia; yet, the specific role of the cytokine milieu in cachexia requires elucidation. This s...

Introduction There is a pressing need for a holistic characterisation of people with incurable cancer. In this group, where quality of life and improvement of symptoms are therapeutic priorities, the physical and biochemical manifestations of cancer are often studied separately, giving an incomplete picture. In order to improve care, spur therapeut...

Surgical site infections (SSI) cause substantial morbidity and pose a burden to acute healthcare services after surgery. We aimed to investigate whether a smartphone-delivered wound assessment tool can expedite diagnosis and treatment of SSI after emergency abdominal surgery. This single-blinded randomised control trial (NCT02704897) enroled adult...

Background: Despite rehabilitation being increasingly advocated for people living with incurable cancer, there is limited evidence supporting efficacy or component parts. The progressive decline in function and nutritional in this population would support an approach that targets these factors. This trial aimed to assess the feasibility of an exer...

Introduction Surgical site infections (SSI) complicate 2%–10% of general surgery cases, and represent a significant burden on acute healthcare services. We aim to investigate if a smartphone-delivered wound assessment tool results in earlier treatment. Method This parallel, single-blinded randomised control trial enrolled adult emergency abdominal...

Treatment of cancer cachexia remains an unmet need. The host-tumour interface and the resulting sequestration of the pro-inflammatory cytokine Il-1β is critical in cachexia development. Neuroinflammation mediated via IL-1β through the hypothalamic pituitary axis results in increased muscle proteolysis and adipose lipolysis, thus creating a prolonge...

Terminal Schwann cells are non-myelinating glial cells localised to the neuromuscular junction. They play an important role in regulating many aspects of neuromuscular junction form and function, in health and during disease. However, almost all previous studies of mammalian terminal Schwann cells have used rodent models. Despite a growing awarenes...

Background Development and spread of cancer is linked to the inflammatory response, in which cytokines serve a key role. The inflammatory response may also form the basis for symptoms of cancer. This systematic review examines the relationship between cytokines and symptoms in incurable cancer. Methods MEDLINE, EMBASE, Cochrane Library, CINAHL, We...

The augmentation of hiatal repair for large hiatus hernia with mesh is controversial. There is some evidence that recurrence rates are less with mesh repair; however, there is a risk of mesh erosion. Complicated erosion may require complex revisional surgery and oesophagogastric resection. We present a novel approach to the treatment of oesophageal...

Background Prognostication in oesophageal cancer on the basis of preoperative variables is challenging. Many of the accepted predictors of survival are only derived after surgical treatment and may be influenced by neoadjuvant therapy. This study aims to explore the relationship between pre-treatment endoscopic tumour morphology and postoperative s...

Large-scale data analysis of synaptic morphology is becoming increasingly important to the field of neurobiological research (e.g. ‘connectomics’). In particular, a detailed knowledge of neuromuscular junction (NMJ) morphology has proven to be important for understanding the form and function of synapses in both health and disease. The recent intro...

Background: Cancer cachexia is a poorly understood metabolic consequence of cancer. During cachexia, different adipose depots demonstrate differential wasting rates. Animal models suggest adipose tissue may be a key driver of muscle wasting through fat-muscle crosstalk, but human studies in this area are lacking. We performed global gene expressio...

Sarcopenia is described as the progressive and generalised loss of skeletal muscle mass and strength (Santilli et al, 2014), which often accompanies liver cirrhosis. Cardiopulmonary Exercise Testing (CPET) is a fundamental clinical tool used to assess exercise capacity and is key in predicting surgical outcomes (Ney et al, 2016). Primary aim - Ass...

Cancer cachexia is a major cause of patient morbidity and mortality, with no efficacious treatment or management strategy. Despite sharing pathophysiological features with a number of neuromuscular wasting conditions, including age-related sarcopenia, the mechanisms underlying cachexia remain poorly understood. Studies of related conditions suggest...

Background The aim of our study was to use a modified Delphi process to determine the research priorities amongst benign upper gastrointestinal (UGI) surgeons in the United Kingdom. Methods Delphi methodology may be utilised to develop consensus opinion amongst a group of experts. Members of the Association of Upper Gastrointestinal Surgeons of Gr...

Sarcopenia is described as the progressive and generalised loss of skeletal muscle mass and strength (Santilli et al, 2014), which often accompanies liver cirrhosis. Cardiopulmonary Exercise Testing (CPET) is a fundamental clinical tool used to assess exercise capacity and is key in predicting surgical outcomes (Ney et al, 2016). Primary aim - Ass...

Introduction Surgery (oesophagectomy), with neoadjuvant chemo(radio)therapy, is the main curative treatment for patients with oesophageal cancer. Several surgical approaches can be used to remove an oesophageal tumour. The Ivor Lewis (two-phase procedure) is usually used in the UK. This can be performed as an open oesophagectomy (OO), a laparoscopi...

Background Despite clinical research being advocated as a key component of palliative care (Payne, Preston, Turner & Rolls, 2013), most patients under the care of palliative care services will not have the opportunity to participate in research. Of the 200 plus UK hospices, few patients get the opportunity to actively participate in research for mu...

Background Rehabilitation is an essential component of palliative care (Tiberini & Richardson, 2015), however, data on efficacy and key components are lacking (Salakari, Surakka, Nurminen et al., 2015). There is a strong argument that any rehabilitation programme should combine exercise and nutrition, which together may improve physical function an...

Cachexia is a multifactorial wasting syndrome associated with high morbidity and mortality in patients with cancer. Diagnosis can be difficult and, in the clinical situation, usually relies upon reported weight loss. The ‘omics’ technologies allow us the opportunity to study the end points of many biological processes. Among these, blood-based meta...

Introduction National data suggest that surgical site infection (SSI) complicates 2%–10% of general surgery cases, although the patient-reported incidence is much higher. SSIs cause significant patient morbidity and represent a significant burden on acute healthcare services, in a cohort predominantly suitable for outpatient management. Over three-...

Cachexia affects the majority of patients with advanced cancer. It leads to poor surgical and oncological outcomes, and negatively affects quality of life. It has long been reported that components of the host immune system, including pro-inflammatory cytokines such as IL-1α, IL-6, TNF-α and INF-γ, participate in the syndrome of cachexia. Yet thera...

Sarcopenia is described as the progressive and generalised loss of skeletal muscle mass and strength (Santilli et al, 2014), which often accompanies liver cirrhosis. Cardiopulmonary Exercise Testing (CPET) is a fundamental clinical tool used to assess exercise capacity and is key in predicting surgical outcomes (Ney et al, 2016). Primary aim - Ass...