IUPHAR ECR review: Cancer-related anorexia-cachexia in cancer patients: Pathophysiology and treatment.

Cancer-related anorexia-cachexia (CRAC) comprises one of the most common syndromes of advanced cancer patients. The prevalence of CRAC increases from 50% to 80% before death. CRAC is associated not only with impaired quality of life in patients and family members but also with shorter survival. The management of CRAC is a great challenge in clinical practice. There are no definite practice guidelines yet for the prevention and treatment of CRAC. A multimodal strategy is the most effective way to treat anorexia-cachexia. Numerous medications have been suggested and used in clinical trials, while others are still being studied on experimental animals. These medications include branched-chain amino acids, eicosapentaenoic acid, thalidomide, cytokine inhibitors, steroids, antiserotoninergic medications, and appetite stimulants. The benefits of supportive care interventions and the advancement of exciting new pharmacological medicines for anorexia-cachexia are becoming more widely recognized. Health care professionals need to be aware of the psychosocial and biological effects of anorexia-cachexia, even though knowledge of the underlying molecular causes of the disorder has advanced significantly.

Validation of the functional assessment of anorexia/cachexia therapy instrument to assess quality of life in maintenance hemodialysis patients with cachexia.

BACKGROUND: Many patients on maintenance hemodialysis (MHD) eventually suffer from cachexia. The Functional Assessment of Anorexia/Cachexia Therapy (FAACT) is a tool used to evaluate the quality of life of patients with cachexia related to various diseases, but its suitability for use in MHD patients has yet to be verified. This study aimed to explore the validation of the FAACT in MHD patients by conducting reliability and validity tests. METHODS: Qualified MHD patients were selected to complete the FAACT and Kidney Disease Quality of Life Short Form 36 (KDQOL-36) questionnaires, and their demographic data and biochemical test results were collected from electronic medical records. Next, the Cronbach's alpha coefficient, paired sample t test and ICC were used to analyze the scale consistency. Additionally, the association between the KDQOL-36 and FAACT was analyzed using Bland-Altman plots and Pearson correlation analysis. Finally, the patients were divided into groups to evaluate discriminant validity. RESULTS: A total of 299 patients were included in this study. The Cronbach's alpha coefficients of the FAACT and its anorexia-cachexia subscale (ACS) were 0.904 and 0.842, respectively, and their ICC exceeded 0.90. The correlation coefficients between the FAACT and its items ranged from 0.146 to 0.631, and the correlation coefficients between the FAACT and KDQOL-36 dimensions ranged from 0.446 to 0.617. The Bland-Altman plots between the FAACT and KDQOL-36 showed that only 3.3% of the points were outside the 95% limits of agreement. The effects of cachexia status (present or absent) on FAACT and ACS scores had effect sizes of 0.54 (P < 0.001) and 0.60 (P < 0.001), respectively. The FAACT and ACS also significantly discriminated between patients with and without inflammation (P < 0.001). CONCLUSIONS: The FAACT and ACS have acceptable reliability and validity in MHD patients and are suitable for measuring the quality of life of MHD patients with cachexia.

[The role of nutrition status correction in the rehabilitation of cancer patients]. / Rol' korrektsii nutritivnogo statusa v reabilitatsii onkologicheskikh patsientov.

Metabolic changes due to the progression of malignant neoplasms and the negative consequences of aggressive methods of its treatment lead to a decrease in food intake in patients, which contributes to the development of anorexia-cachexia syndrome in cancer patients due to complex interactions between pro-inflammatory cytokines and host metabolism. Within the framework of this article, the author analyzes the possibility of the influence of nutritional status in cancer patients. The analysis of the results of the study of a group of cancer patients with various nutritional statuses was carried out. It is concluded that the control and correction of nutritional status should become an integral part of the assessment of the quality of life and meet the needs and expectations of the patient.

Acupuncture for Cancer-Related Anorexia: a Review of the Current Evidence.

PURPOSE OF REVIEW: Loss of appetite/anorexia is extremely common among cancer patients, affecting as many as half of newly diagnosed patients and 70% of patients with advanced disease. Effective management of this disabling symptom of cancer remains a major challenge in the field of oncology. We conducted a systematic review of the current evidence on acupuncture and/or moxibustion as an intervention for cancer-related anorexia. RECENT FINDINGS: Acupuncture, as a part of traditional Chinese medicine practice, has demonstrated effectiveness in managing many cancer- and treatment-related symptoms, especially chemotherapy-induced or postoperative nausea. However, the efficacy of acupuncture in treating cancer-related anorexia/loss of appetite is not clear. The current level of evidence is insufficient to make a definitive conclusion on the benefit of acupuncture/moxibustion for treating chronic cancer-related anorexia/appetite problems. Future large randomized controlled trials of high methodological quality are needed.

Should Loss of Appetite Be Palliated in Patients with Advanced Cancer?

OPINION STATEMENT: Loss of appetite is common among patients with advanced cancer. However, it remains controversial how, when, and if to palliate this symptom. Here, we provide an update on recent as well as past literature to address the question of whether loss of appetite should be palliated in patients with advanced cancer. In our opinion-and as discussed here-we believe that this symptom should be palliated, although perhaps not always with pharmacologic interventions.

Asprosin is associated with anorexia and body fat mass in cancer patients.

PURPOSE: Increasing evidence suggests that many adipokines are involved in cancer-related anorexia and cachexia syndrome (CACS), although the underlying mechanism remains to be clarify. Asprosin is a new peptide hormone mainly secreted by white adipose tissues that can increase appetite and body weight. In this cross-sectional study, we tested whether asprosin may intervene in the development of CACS. METHODS: The fasting plasma asprosin levels were determined via enzyme-linked immune-sorbent assay. Anorexia was determined using the anorexia/cachexia subscale (A/CS) of the functional assessment of anorexia/cachexia therapy (FAACT) questionnaire. The body composition was assessed using bioelectrical impedance analysis. The association of plasma asprosin with anorexia, cachexia, and nutritional status was analyzed. RESULTS: One hundred twenty treatment-naïve patients with pathological confirmed gastrointestinal or lung cancer and 14 mild gastritis patients were recruited. We found no significant difference in asprosin levels between subgroups of patients by age, sex, cancer types or stage. Correlation analysis suggested that asprosin levels were positively associated with body fat mass (r = 0.248, p = 0.043). No correlations were found between asprosin levels and hemoglobin, white blood cell count, blood platelet count, albumin, C-reactive protein, glucose, cholesterol, triglyceride, high density lipoprotein, low density lipoprotein, body mass index, body fat percentage, protein, skeletal muscle, muscle mass, lean body mass, and basal metabolic rate. Furthermore, asprosin levels were not significantly different between patients with or without cachexia. However, patients with anorexia had significantly lower asprosin levels compared with patients without anorexia. No significant difference in asprosin levels between gastritis and gastric cancer patients. Similarly, no significant change of asprosin levels occurred postoperatively in 10 gastric cancer patients. CONCLUSIONS: Patients with anorexia had significantly lower asprosin levels compared with patients without anorexia. We therefore speculated that asprosin might intervene in the development of cancer anorexia and serve as a potential therapeutic target.

New horizons in appetite and the anorexia of ageing.

Appetite drives essential oral nutritional intake. Its regulation is complex, influenced by physiology, hedonism (the reward of eating) and learning from external cues within a person's society and culture. Appetite loss is common in the older population and not always attributable to medical conditions or treatment. Although the physiological basis of the anorexia of ageing (loss of appetite due to the ageing process) has been established, the effect of ageing on hedonism and external cues, which may be equally important, is less well understood. The anorexia of ageing is associated with reductions in dietary diversity and oral intake, and increased risk of malnutrition, sarcopenia and frailty. Early identification of poor appetite could allow timely intervention before weight loss occurs. There is no standardised tool for assessing appetite in clinical settings at present but the 4-item Simplified Nutritional Appetite Questionnaire (SNAQ) has the potential to be used in this way. This review, designed for clinicians, will discuss the regulation of appetite and the pathogenesis of the anorexia of ageing. It will describe the current evidence for interventions to manage the anorexia of ageing, which is limited, with little benefit reported from individual studies of education, physical activity and medication. There is some positive evidence for flavour enhancement, fortified food and oral nutritional supplements but mainly within single studies. Looking ahead, the aim is to develop multicomponent approaches to the treatment of the anorexia of ageing based on growing understanding of the role of physiological signalling, hedonism and external cues.

Differential effects of heat in the phases of the light-dark cycle in the activity-based anorexia model.

BACKGROUND: This research builds on the studies on ambient temperature as a key influence in the recovery of rodents exposed to the activity-based anorexia (ABA) model. The ABA model is an experimental paradigm in which rodents under a restricted feeding schedule and with free access to an activity wheel show signs that parallel those of anorexia nervosa in humans. OBJECTIVE: The present study focuses on the effects of applying heat during the different phases of the dark-light cycle in the activity levels, body weight, food intake, body temperature, and recovery rates of 30 male rats submitted to ABA. METHOD: After reaching a 20% weight loss criterion, animals were randomly assigned to three experimental conditions: (a) continuous warming, (b) warming exclusively during the light phase, or (c) warming exclusively during the dark phase. RESULTS: Differential effects were found depending on the modalities of warming: in comparison with either light or dark warming, continuous warming significatively decreased activity, facilitated weight gain, and maintained body temperature. Transient effects of warming were found both in the groups warmed either during light or dark periods exclusively. DISCUSSION: The results suggest that both light and dark warming did not promote recovery in animals exposed to ABA. Evidence about the beneficial effects of continuous warming are in line with previous research and reinforces adding external heat as a useful tool in the treatment of anorexia nervosa.

[The effects of the psychiatric hospital on an adolescent's sexual development.] / Les effets de l'institution psychiatrique sur la trajectoire sexuelle d'un adolescent.

Diego, a young adolescent, is hospitalised in a psychiatric unit for anorexia. The diagnosis of anorexia, as well as medical practices, result in resistance from the young man, for whom being "anorexic" seems incompatible with a masculine and heterosexual vision of oneself. His passage through the psychiatric unit is then not without effect on his sexual development.

FAACT-Anorexia Cachexia Scale: Cutoff Value for Anorexia Diagnosis in Advanced Non-Small Cell Lung Cancer Patients.

Lung cancer (LC) has a high rate of anorexia, which negatively affects quality-of-life and prognosis; however prevalence values may vary as per diagnostic test. There is no standard for anorexia diagnosis, currently the anorexia cachexia scale (A/CS) has been proposed as a tool for diagnosing anorexia with a consensus cutoff value of ≤24, nonetheless a validated cutoff value is required. The A/CS was evaluated in advanced Non-Small Cell Lung Cancer (NSCLC) patients to establish a cutoff value. The appetite item from the QLQ-C30 questionnaire and survival served as a standard reference. The cutoff value was associated with clinical and nutritional characteristics along with quality-of-life. Three hundred and twelve (312) NSCLC patients were evaluated. The mean A/CS value was 31 ± 9 and the identified cutoff value was 32.5 (sensitivity: 80.3% and specificity: 85%). The proportion of anorexia accurately diagnosed with the cutoff value of 24 was 26%, while with 32 it was 50%. The A/CS cutoff value of 32 was associated with clinical parameters, nutritional consumption, and quality-of-life, and independently associated with overall survival. A score of ≤32 in the A/CS is proposed for anorexia diagnosis in order to identify patients at risk of complications involving malnutrition related to LC.

Comprehensive validation of the functional assessment of anorexia/cachexia therapy (FAACT) anorexia/cachexia subscale (A/CS) in lung cancer patients with involuntary weight loss.

PURPOSE: Comprehensive (qualitative and quantitative) assessments of the 12-item functional assessment of anorexia/cachexia therapy (FAACT) anorexia/cachexia subscale (A/CS) and relevant subscales were undertaken for use in constructing potential endpoints in clinical trials of non-small cell lung cancer (NSCLC) with involuntary weight loss. METHODS: Eleven participants (≥ 18 years) from six clinical sites with a diagnosis of stage III unresectable or stage IV NSCLC and involuntary weight loss (either ≥ 5% body weight loss within six months prior to screening or screening BMI < 20 kg/m2) were interviewed to evaluate the content validity of the A/CS domain. A psychometric evaluation was conducted on the A/CS domain, and symptoms and concerns subscales, using data from previously completed phase III clinical trials (ROMANA1 [N = 474] and ROMANA2 [N = 488]). RESULTS: Anorexia-related symptoms were highly relevant to participants and had important impacts on their lives including energy levels, and physical, social, and psychological functioning. The majority of participants endorsed the A/CS domain items and found them to be easily understood, relevant, and comprehensive. Confirmatory factor analyses established that the A/CS symptoms and concerns subscales provided an acceptable fit as single factor models in ROMANA1 and ROMANA2. Reliability, validity, and responsiveness were established for the 12item A/CS domain, 5item anorexia symptoms subscale, and 4-item anorexia concerns subscale. CONCLUSIONS: These scales have good content validity, favorable psychometric properties, and can be used for characterizing the effect of treatment on anorexia symptoms and/or anorexia-related concerns in patients with NSCLC.

Are the therapeutic strategies in anorexia of ageing effective on nutritional status? A systematic review with meta-analysis.

BACKGROUND: Anorexia of ageing (AA) may be considered as a risk factor for frailty and has an important impact on quality of life, morbidity and mortality. METHODS: A systematic review and a meta-analysis were performed to summarise the results from several trials on the effectiveness of treatments in AA, as associated with depression, sensory impairment of taste and smell, decreased appetite or early satiety, and disability. Eligible studies were required to report baseline and follow-up values, the mean change (∆-change) from baseline, and/or the mean difference among intervention groups versus control group, concerning food intake (kcal/daily) and/or nutritional outcomes, such as body weight, body mass index, albumin and Mini Nutritional Assessment. RESULTS: The systematic review included 20 papers based on different therapeutic approaches concerning food intake and/or nutritional outcomes. The results of the meta-analysis indicate that the interventions for AA have an important impact on body weight [+1.59 kg; 95% confidence interval (CI) = 1.48-+1.71 kg; P < 0.001) and on energy intake (+56.09 kcal; 95% CI = -54.05 to +166.25 kcal; P = 0.32). Regarding secondary outcomes, it was not possible to meta-analyse the limited amount of data availab le. CONCLUSIONS: The different variants of AA need to be defined because diverse therapeutic approaches are available. A more precise definition of the functional impairments associated with AA may allow a more correct decision about the most appropriate therapy to be prescribed. Moreover, this may allow for a more effective performance of the different therapeutic approaches once they are better targeted to the different scenarios of AA.

Novel targeted therapies for cancer cachexia.

Anorexia and metabolic alterations are the main components of the cachectic syndrome. Glucose intolerance, fat depletion, muscle protein catabolism and other alterations are involved in the development of cancer cachexia, a multi-organ syndrome. Nutritional approach strategies are not satisfactory in reversing the cachectic syndrome. The aim of the present review is to deal with the recent therapeutic targeted approaches that have been designed to fight and counteract wasting in cancer patients. Indeed, some promising targeted therapeutic approaches include ghrelin agonists, selective androgen receptor agonists, ß-blockers and antimyostatin peptides. However, a multi-targeted approach seems absolutely essential to treat patients affected by cancer cachexia. This approach should not only involve combinations of drugs but also nutrition and an adequate program of physical exercise, factors that may lead to a synergy, essential to overcome the syndrome. This may efficiently reverse the metabolic changes described above and, at the same time, ameliorate the anorexia. Defining this therapeutic combination of drugs/nutrients/exercise is an exciting project that will stimulate many scientific efforts. Other aspects that will, no doubt, be very important for successful treatment of cancer wasting will be an optimized design of future clinical trials, together with a protocol for staging cancer patients in relation to their degree of cachexia. This will permit that nutritional/metabolic/pharmacological support can be started early in the course of the disease, before severe weight loss occurs. Indeed, timing is crucial and has to be taken very seriously when applying the therapeutic approach.

The management strategies of cancer-associated anorexia: a critical appraisal of systematic reviews.

BACKGROUND: Cancer-related anorexia remains one of the most prevalent and troublesome clinical problems experienced by patients with cancer during and after therapy. To ensure high-quality care, systematic reviews (SRs) are seen as the best guide. Considering the methodology quality of SRs varies, we undertook a comprehensive overview, and critical appraisal of pertinent SRs. METHODS: Eight databases (between the inception of each database and September 1, 2017) were searched for SRs on the management of cancer-related anorexia. Two researchers evaluated the methodological quality of each SR by using the Revised Assessment of Multiple Systematic Reviews (R-AMSTAR) checklist. Characteristics of the "high quality" SRs were abstracted, included information on relevant studies numbers, study design, population, intervention, control, outcome and result. RESULTS: Eighteen SRs met the inclusion criteria. The R-AMSTAR scores of methodological quality ranged from 18 to 41 out of 44, with an average score of 30. Totally eight SRs scored ≥31 points, which showed high methodological quality, and would be used for data extraction to make summaries. Anamorelin had some positive effects to relieve cancer anorexia-cachexia syndrome (CACS) and improve the quality of life (QoL). Megestrol Acetate (MA) could improve appetite, and was associated with slight weight gain for CACS. Oral nutritional interventions were effective in increasing nutritional intake and improving some aspects of QoL in patients with cancer who were malnourished or at nutritional risk. The use of thalidomide, Eicosapentaenoic Acid, and minerals, vitamins, proteins, or other supplements for the treatment of cachexia in cancer were uncertain, and there was inadequate evidence to recommend it to clinical practices, the same situation in Chinese Herb Medicine and acupuncture (acupuncture and related therapies were effective in improving QoL) for treating anorexia in cancer patients, warranting further RCTs in these areas. CONCLUSIONS: Anamorelin, MA, oral nutrition interventions, and acupuncture could be considered to be applied in patients with cancer-related anorexia. Future RCTs and SRs with high quality on the pharmaceutical or non-pharmaceutical interventions of anorexia in cancer patients are warranted.

Allocating a scarce mental health treatment to the underweight and overweight.

BACKGROUND: This is one of a number of programmatic studies on the allocation of scarce medical resources. AIMS: This study investigated whether certain characteristics about patients influence the priority they are assigned for a scarce mental health treatment. Similar studies for physical treatments have found that young, poor, and mentally healthy patients are given the highest priority. METHOD: Each participant completed one questionnaire where they ranked a list of eight hypothetical patients in order of priority for treatment for anorexia or obesity. The patients varied on three dimensions: age, social class and mental health history. This involved a ranking of prioritisation for treatment. RESULTS: Participants gave the young patients, from a low social class background, who had a mental health history the highest priority for treatment. This is in contrast to previous studies indicating that the mentally unwell are discriminated against. CONCLUSIONS: Participants seemed to be using social class as a proxy measure of ability to pay which they weighted very highly.

Use of Functional Foods and Oral Supplements as Adjuvants in Cancer Treatment.

In cancer patients treated with radiotherapy to the abdominopelvic region, dietary modifications and the use of functional foods (fortified food with added ingredients to provide specific health improving benefits, such as antioxidants, omega-3 fatty acids, and glutamine), may contribute to the improvement of the toxic effects of treatment, including nausea, diarrhea, and constipation, among others. With the aim of analyzing which coadjuvant foods benefit these patients, scientific evidence was gathered by a group of experts. For these patients, the authors recommend a diet that includes sufficient foods rich in antioxidants and polyphenols instead of supplements. Docosahexaenoic and eicosapentaenoic acids have proven useful for the management of anorexia/cachexia in pancreatic cancer patients. Probiotics composed of Lactobacillus spp. and Bifidobacterium spp. are regarded as safe even in patients with neutropenia and have been proven to decrease gastrointestinal symptoms. Several factors should be considered before probiotic supplementation, these include the stage of the disease, radiation dose, and symptomatology of each patient. There is no demonstrated clear benefit to the use of glutamine, so it is not recommended due to its high cost.

[Body-oriented psychotherapy in the global treatment of children with anorexia]. / La médiation corporelle dans la prise en charge globale de jeunes souffrant d'anorexie mentale.

Body-oriented psychotherapy has been an innovative practice in the treatment of anorexia for around ten years. This body-oriented and relational care is carried out on medical prescription individually or in groups, once or twice a week for six to eighteen months. The session comprises different moments of welcome, movement and exchange. This approach constitutes an interesting therapy which needs to be validated by research.

Perception of Peripersonal and Interpersonal Space in Patients with Restrictive-type Anorexia.

This study examines whether the perception of peripersonal action-space and interpersonal social-space is modified in patients with restrictive-type anorexia in two experimental conditions using videos. First, participants stopped the video of an approaching stimulus when they felt the distance to be comfortable for interacting with it (first-person perspective). Second, participants stopped the video when an observed individual approaching a stimulus, or being approached by it, was at a comfortable distance (third-person perspective). In the first-person perspective, the results showed an estimation of peripersonal space that did not differ from controls when an object was approaching and an increase in interpersonal space compared with controls when a male or female individual was approaching. In the third-person perspective, both individual-object and individual-individual distances were larger in anorexic patients. These results indicate a specific deficit in adjusting interpersonal distances in both the first-person and third-person perspectives. Copyright © 2017 John Wiley & Sons, Ltd and Eating Disorders Association.

[Novelties 2016 in pediatrics]. / Pédiatrie.

Nutrition is central in pediatric care : essential for growth and development, it plays also a role in the prevention of many diseases.Even if breastfeeding is highly recommended, its implementation may be difficult in particular for premature and ill newborns. The creation of a specific unit for breastfeeding support in neonatology allows to help mothers willing to nurse and to improve the rate of breastfeeding for these vulnerable infants.Eating disorders represent an important challenge for patient care. Early detection and rapid management of anorexia is essential for the prognosis. This article describes the challenges and the practical process underlying the development of a practical guideline to manage children and adolescents hospitalized for anorexia.

La nutrition est un thème central en pédiatrie : essentielle pour la croissance et le développement de l'enfant, elle joue également un rôle dans la prévention de nombreuses maladies.Bien que fortement recommandée, la mise en place de l'allaitement peut être difficile en particulier chez les nouveau-nés prématurés ou malades. La création d'une unité de soutien à l'allaitement en néonatologie a permis d'offrir un soutien aux mères souhaitant allaiter et d'améliorer le taux de lactation. Les troubles du comportement alimentaire représentent un important challenge de prise en charge. Une détection et une prise en charge rapide de l'anorexie sont essentielles pour le pronostic. Cet article décrit les enjeux et le processus parcouru pour élaborer un guide de prise en charge des enfants et adolescent(e)s hospitalisé(e)s pour une anorexie.