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Cachexia

From Molecular Insights to Clinical Strategies: Delve into the complexities of cachexia, encompassing cancer cachexia, molecular mechanisms, and evolving therapeutic approaches. Discover the forefront of research aimed at understanding and combating this debilitating condition.

Review of the endocrine organ-like tumour hypothesis of cancer cachexia in pancreatic ductal adenocarcinoma

Pancreatic ductal adenocarcinoma, PDAC, is one of the most fatal types of solid tumours. It is also linked to a high prevalence of cachexia, with around 80% of PDAC patients exhibiting cachexia. There is one hypothesis, the endocrine organ–like tumour hypothesis, which aims to explain the reasons behind cancer cachexia occurring during pancreatic ductal adenocarcinoma. Some of the reasons include metabolites, epigenetic changes, hormonal disturbance and genetic instability may be behind the development of cancer cachexia. Generally, the belief is held that metabolic disruption is the process behind cachexia development, but it is also believed there is not one single factor that triggers it. This review by Yu Y et al aimed to synthesise an understanding of cancer cachexia development and the response of cachexia to current available treatments.
Read MoreReview of the endocrine organ-like tumour hypothesis of cancer cachexia in pancreatic ductal adenocarcinoma

Malnutrition risk and frailty in head and neck cancer patients: a review

For patients with head and neck cancer, malnutrition and frailty are linked with adverse treatment outcomes, higher mortality rates, complications post-surgery and generally lower quality of life. However, the relationship between malnutrition and frailty is not fully known. It is, however, clear that these two conditions often coexist, suggesting they may share similar risk factors. In this study on 197 patients, it was found that the risk of malnutrition is strongly positively associated with frailty. However, some other interesting factors were discovered. Alcohol consumption was shown to present a greater risk of developing malnutrition, but on the other hand, alcohol consumption seems protective for being frail. Overall, these conditions often coexist but do not always fully overlap: screening for both conditions is therefore recommended. This review by Dewansingh P et al aimed to understand the relationship between the risk of malnutrition and frailty in patients with head and neck cancer.
Read MoreMalnutrition risk and frailty in head and neck cancer patients: a review

Cachexia staging score and cancer survival: a review

Cancer cachexia has no simple criteria to distinguish its severity in patients. Diagnostic criteria generally includes observing factors such as weight loss, fatigue, abnormal levels of albumin, reduced food intake and others. However, this study explored the cachexia staging score, a method of diagnosing cancer cachexia severity. This score explores strength, walking, rising from a chair, climbing up stairs and how often the patients fall. This allows clinicians to understand the patient’s muscle function. In this study, the cachexia staging score was testing in patients with advanced cancer who are receiving palliative care, to assess its usefulness in these patients. Here, the cachexia staging score was excellent at predicting life expectancy in the patients with advancing cancer receiving palliative care, and was able to classify patients according to their different stages of cachexia. This review by Ueshima J et al. aimed to assess whether the cachexia staging score could be applied to patients with advanced cancer under palliative care.
Read MoreCachexia staging score and cancer survival: a review

Hand grip strength-based cachexia index: a review

Cancer cachexia can be mainly categorised with the occurrence of muscle loss, malnutrition and systemic inflammation. Its prognosis can be assessed through the cachexia index, but the use of this index is limited due to it being a complicated procedure with high testing costs. This study explored using a hand grip strength-based cachexia index, testing it with 14, 682 cancer patients. A low hand grip strength index score was found to be associated with high systemic inflammation, high levels of malnutrition and co-morbidities, implying that this index may be associated with disease progression. Overall, using the hand grip strength index for cachexia reflects the muscular and inflammatory conditions of cachexia in one assessment, rather than using multiple such as serum albumin testing, in a simple, non-invasive measure. Furthermore, there is a potential that hand grip strength can provide information about the prognosis of other malignancies. This review by Xie H et al. aimed to compare the hand grip strength-based cachexia index to the original cachexia index to understand its benefits.
Read MoreHand grip strength-based cachexia index: a review

Sarcopenia and cachexia prevalence in older patients with colorectal cancer

Colorectal cancer (CRC) incidence has been shown to increase with age, an association which is clinically significant in the context of global ageing populations. Frailty, defined as increased vulnerability to stressors like surgery, is a marker associated with poor outcomes in patients with CRC. Sarcopenia, characterised by an age- and disease-related loss in muscle function and mass, has been identified as a major contributor to frailty. Patients with cancer also commonly experience cancer cachexia, i.e., loss of fat and muscle mass. This syndrome has also been associated with poorer survival rates for cancer patients. As such, both sarcopenia and cachexia constitute potentially modifiable risk factors of negative surgical outcomes. This study aimed to examine the prevalence of preoperative sarcopenia and cachexia in a group of older (≥65 years) vulnerable patients undergoing resection for localized CRC.
Read MoreSarcopenia and cachexia prevalence in older patients with colorectal cancer

Amino acids in cancer and cachexia: a review

Amino acid metabolism is hugely altered in tumours. Cancer cells use amino acids for energy production, which supports cell proliferation. In this sense, their amino acid dependency provides a metabolic vulnerability for treatment. Research has been aimed at starving cancerous cells of amino acids to improve cancer treatment outcomes. However, supplementing amino acids has also shown benefits both in vivo and in vitro. Further research into amino acid supplementation is needed, as deprivation exacerbates cancer cachexia, a risk best avoided in cancer treatment. Supplementing branched-chain amino acids has been proved as beneficial in hepatocellular carcinoma, and an essential amino acid rich diet has demonstrated decreased tumour growth in mice. Understanding more about amino acid metabolism in cancer may provide more efficient, personalised treatments for cancer patients. This review by Ragni M et al. aimed to discuss amino acid deprivation and supplementation in reducing tumour growth, underscoring the complexity of the metabolic pathways involved.
Read MoreAmino acids in cancer and cachexia: a review

Muscle depleted obesity and colorectal cancer: a review

Colorectal cancer is the second leading cause of cancer death in the world. However, incidence rates and mortality can both be significantly reduced through adhering to healthy lifestyle recommendations. In this study, 82 people were included, where their nutritional profile was evaluated to assess their risk of colorectal cancer. This is because obesity is one of the biggest risk factors for colorectal cancer, and when associated with sarcopenia, there are usually worse health outcomes. This study has therefore highlighted the need for understanding muscle composition in obese individuals when screening for cancer, as this may affect outcomes. Furthermore, this study underscores the necessity to aim for health lifestyles through weight control and physical exercise, to decrease incidence and mortality of diseases such as colorectal cancer. This review by Santos M et al. aimed to evaluate nutritional profiles for those screening for colorectal cancer, to aid a better understanding of the risk factors behind this cancer.
Read MoreMuscle depleted obesity and colorectal cancer: a review

Anamorelin in cancer cachexia and low body mass index: a review

In this study, 102 Japanese patients with gastrointestinal or non-small cell lung cancer with cancer cachexia were used to test anamorelin. Anamorelin is a selective ghrelin receptor agonist and is taken orally. This drug is generally known to increase appetite and was hypothesised to help with improving cancer cachexia as well as increasing the patients’ low body mass index. It was found that improvements in their body weight were durable for up to 24 weeks, and overall, the patients reported a better appetite and overall well-being. The drug was also generally well tolerated, with around 37% of patients experiencing adverse side effects. Most commonly, these included symptoms such as glycosylated haemoglobin increase, peripheral oedema and constipation. This review by Naito T et al. aimed to understand the benefits of anamorelin in cancer cachexia patients with improving their low body mass index.
Read MoreAnamorelin in cancer cachexia and low body mass index: a review

Weight loss as a precursor to cancer diagnosis: a review

Weight loss is clearly related to cancer, yet there is very little data concerning when and at what stage weight loss should be considered a sign of a need to diagnose cancer. In this study of 43,302 patients, it was found that there was a linear increase in the chance of being diagnosed with cancer compared to the amount of weight lost. This finding was independent of any co-factors, such as age, sex, original weight or co-morbidities. Therefore, it is clear that the percentage of weight lost must be focused on, rather than a guideline with an arbitrary cut-off point for a cancer diagnosis. It could be possible to trigger an alert for patients who lose certain percentages of weight over specified periods of time. This review by Nicholson B et al aimed to understand the diagnostic value of weight loss in relationship to cancer.
Read MoreWeight loss as a precursor to cancer diagnosis: a review

Targeting oxidative stress in cancer- and chemotherapy-induced muscle wasting: a review

Cancer is often associated with cachexia, a wasting syndrome which is multifactorial and cannot be resolved with simple nutritional aid. It causes loss of muscle mass and is the cause of death for almost a third of cancer patients. However, cachexia is very complex. This muscle-wasting disorder has many underlying mechanisms, whether cancer-induced or chemotherapy induced. Heighted protein catabolism and reduced anabolism, as well as disrupted energy metabolism, are associated with cachexia, but the mechanisms underlying these changes are not fully known. Inflammation and oxidative stress are believed to be important within the mechanisms. This review by Huot J et al. aimed to evaluate the mechanisms underlying cancer cachexia, particularly discussing the role of oxidative stress.
Read MoreTargeting oxidative stress in cancer- and chemotherapy-induced muscle wasting: a review

Experience of renal cachexia in end-stage renal disease and the interrelated experience of their carers: a review

Renal cachexia often occurs in end-stage renal disease, yet there are few guidelines for clinicians in how to treat and manage this condition. To ensure a patient-centric approach, understanding the experiences of patients with renal cachexia, as well as their carers, will help to implement the most beneficial guidelines possible. This study focuses on assessing quality of life outcomes, including psychological and social factors, in an attempt to raise awareness about the impact of cancer cachexia. This information aims to inform the management of renal cachexia, as well as general holistic care within the field of nephrology. This review by Blair C et al. aimed to synthesize the lived experiences of renal cachexia in patients suffering with end-stage renal disease, as well as that of their carers.
Read MoreExperience of renal cachexia in end-stage renal disease and the interrelated experience of their carers: a review

The role of exercise and myokine production in counteracting frailty

Recent studies have identified energy dysregulation as one of the principle drivers of frailty. Exercise, the most effective tool to combat frailty, is associated with energy metabolism upregulation and reduction of inflammation. It has been hypothesised this therapeutic effect is linked to the production of myokines by skeletal muscle in response to acute and chronic exercise. Evidence has concluded that myokines play a crucial role in upholding energy metabolism and combating inflammation. However, despite this, only a limited number of studies have examined the changes in myokine concentrations with exercise in older adults. This review aims to summarise evidence supporting an association between energy metabolism and frailty. It also assesses the role of myokines, released during exercise, in combating frailty.
Read MoreThe role of exercise and myokine production in counteracting frailty

Cancer cachexia knowledge and practice gaps: a review

Cancer cachexia is a wasting disorder, where nutritional interventions cannot fully aid in restoring weight in patients. It severely impacts quality of life and survival rates of patients. In this study, a 58-question questionnaire was completed by clinicians to understand the knowledge and practice gaps within the treatment of cancer cachexia. Some issues raised included the lack of a standardised definition of cancer cachexia for diagnosis, with 43% of respondents stating that low levels of attention are given to providing such a diagnosis. Furthermore, it was reported that screening for cachexia was not completed routinely, among other practice gaps. This review by Baracos VE et al. aimed to highlight the gaps in understanding of cancer cachexia that clinicians face worldwide.
Read MoreCancer cachexia knowledge and practice gaps: a review

Body mass index, weight loss and survival in advanced lung cancer: a review

For patients with advanced-stage cancer, weight loss and lower body mass index has been associated with shorter rates of survival. On the other hand, obesity has been associated with longer survival. Weight loss or cachexia could therefore be used as a prognostic tool, although it has not yet been studied much in clinical trials. It is predicted to be due to the fact that decreased muscle mass is a predictor of shortened survival, as well as lowered nutrient stores and activity level. However, further research is required into understanding weight loss in relation to cancer survival rates, especially in the context of therapies such as chemotherapy, as it is not fully known how this interacts with body mass. This review by Oswalt C et al. aimed to explore the relationship between body mass index, weight loss and survival rates in advanced lung cancer.
Read MoreBody mass index, weight loss and survival in advanced lung cancer: a review

Cancer cachexia and upper gastrointestinal cancers: a review

Globally, there are over 1.5 million new cases of gastric and oesophageal cancer annually. These cases (especially advanced cases) are often associated with cancer cachexia, a multifactorial syndrome that leads to progressive wasting which cannot be fully reverse through nutritional interventions. It is also responsible for around 20% of cancer deaths. Yet, the understanding of cancer cachexia is often neglected in treatment. This presents an issue as cytotoxic drug doses are most commonly calculated based on body surface area, not taking into account decreasing mass. Furthermore, understanding cancer cachexia would allow for the improvement of therapeutic options, which are currently little researched, including exercise- and nutrition-based interventions, as well as targeted treatments such as anti-IL1 α and anti-GDF-15. Even for patients with incurable cancers, the management of cachexia wasting can improve quality of life. This review by Brown LR et al. aimed to highlight the necessity of understanding the progression of cancer cachexia in association with diseases such as gastric and oesophageal cancer, as well as the possible future research directions associated with aiding in these conditions.
Read MoreCancer cachexia and upper gastrointestinal cancers: a review

Cancer cachexia and exercise-based therapy: a review

Cancer cachexia is a multifactorial syndrome that leads to progressive wasting which cannot be fully reverse through nutritional interventions. There is currently no clear method for the management of cachexia, but exercise seems to hold promising potential. Exercise may provide anti-inflammatory and anti-oxidative effects, which may prove important in aiding with cachexia due to its correlation with inflammation and oxidative stress. Furthermore, exercise improves muscle strength and function, which can improve quality of life for those with cancer cachexia. However, there is very scarce evidence for this, and even some evidence contradicting the benefit of exercise due to the risk of over-extending the patients. This review by Murphy BT et al. aimed to shine light on both sides of the complex discussion surrounding the benefits of exercise in aiding with cancer cachexia.
Read MoreCancer cachexia and exercise-based therapy: a review

CACHEXIA DEFINITION

Cachexia has been defined as a loss of lean tissue mass, involving a weight loss greater than 5% of body weight in 12 months or less in the presence of chronic illness or as a body mass index (BMI) lower than 20 kg/m2. In addition, usually three of the following five criteria are required: decreased muscle strength, fatigue, anorexia, low fat-free mass index, increase of inflammation markers such as C-reactive protein or interleukin (IL)-6 as well as anaemia or low serum albumin.

Cachexia can occur in most major diseases including infections, cancer, heart disease, chronic kidney disease, chronic obstructive pulmonary disease, and stroke.

REFERENCES
Evans WJ, Morley JE, Argiles J, Bales C, Baracos V, Guttridge D, et al. Cachexia: a new definition. Clin Nutr 2008;27:793–799

Fearon K, Strasser F, Anker SD, Bosaeus I, Bruera E, Fainsinger RL, Jatoi A, Loprinzi C, MacDonald N, Mantovani G, Davis M, Muscaritoli M, Ottery F, Radbruch L, Ravasco P, Walsh D, Wilcock A, Kaasa S, Baracos VE. Definition and classification of cancer cachexia: an international consensus. Lancet Oncol 2011;12:489–495.

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