Search Results (22)

Background/Objectives: Colorectal cancer (CRC) is associated with anorexia–cachexia syndrome, which negatively affects health-related quality of life (HRQoL). This study aimed to evaluate HRQoL and functional status in CRC patients undergoing chemotherapy who were eligible for oral nutritional supplementation (ONS). Methods: In this prospective, randomized study, 72 patients with stage II–IV CRC were enrolled (40 intervention group [IG], 32 control group [CG]). IG received ONS (2 × 125 mL/day, 600 kcal, 36 g protein) for 12 weeks, while CG received dietary counseling only. HRQoL was assessed every 4 weeks with the Functional Assessment of Anorexia/Cachexia Therapy (FAACT, version 4.0). Functional status was evaluated with the Karnofsky scale. Nutritional status was assessed using the Subjective Global Assessment (SGA), Nutritional Risk Screening (NRS-2002), and body mass index (BMI), and appetite was assessed on a visual analogue scale (VAS). Clinical Trial Registration: ClinicalTrials.gov, NCT02848807. Results: Mean FAACT score did not differ significantly between groups over 12 weeks (101.0 ± 22.8, 95% CI: 94.6–107.4 vs. 105.1 ± 21.4, 95% CI: 99.1–111.1; p = 0.06). However, the observed difference corresponded to an effect size at the lower bound of the moderate range. However, minimally important difference (MID) analysis demonstrated that clinically meaningful improvement was significantly more frequent in IG than in CG for global FAACT (32% vs. 8%; p = 0.03, OR = 5.50, 95% CI: 1.10–27.62, φ = 0.29), physical well-being (32% vs. 8%; p = 0.03, OR = 5.50, 95% CI: 1.10–27.62, φ = 0.29), and emotional well-being (38% vs. 4%; p = 0.002, OR = 14.86, 95% CI: 1.79–123.36, φ = 0.40). Functional well-being and anorexia/cachexia concerns showed favorable, but nonsignificant, trends (FWB improvement: 29% vs. 8%, p = 0.05, OR = 4.79, 95% CI: 0.95–24.27, φ = 0.26; ACS deterioration: 3% vs. 20%, p = 0.07, OR = 0.12, 95% CI: 0.01–1.11, φ = 0.28). HRQoL correlated positively with nutritional status, appetite, and functional performance, while Karnofsky scores remained stable in both groups. Conclusions: ONS did not significantly change the mean QoL scores at the group level but increased the proportion of patients achieving clinically meaningful improvement, particularly in the physical and emotional domains. These findings suggest that ONS may benefit selected patients who respond to nutritional interventions, underscoring the clinical relevance of individualized nutrition strategies in oncology. Full article

Cancer cachexia (CC) is a multifactorial, multi-organ syndrome characterized by systemic inflammation, metabolic dysregulation, anorexia, and progressive depletion of skeletal muscle and adipose tissue. Despite its high prevalence among patients with advanced malignancies, effective therapeutic options remain limited. Recent studies have elucidated the molecular underpinnings of CC and the therapeutic potential of natural herbs, highlighting the involvement of central nervous system regulation, adipose tissue, immune responses, gut microbiota, skeletal muscle, and disruptions in anabolic–catabolic signaling pathways such as mTOR, UPS, NF-κB, and STAT3. Persistent inflammation induces E3 ubiquitin ligases (Atrogin-1/MuRF-1) through cytokines including IL-6 and TNF-α, thereby impairing muscle homeostasis, while suppression of anabolic cascades such as IGF-1/mTOR further aggravates muscle atrophy. The limited efficacy and adverse effects of synthetic agents like megestrol acetate underscore the value of herbal therapies as safer adjunctive strategies. Botanicals such as Coicis Semen, Scutellaria baicalensis, and Astragalus demonstrate anti-inflammatory and muscle-preserving activities by modulating NF-κB, IL-6, and oxidative stress signaling. Numerous investigations indicate that these herbs downregulate MuRF-1 and Atrogin-1 expression, enhance appetite, and attenuate muscle loss, though they exhibit minimal influence on tumor suppression. While promising, current evidence remains largely preclinical and mechanistic validation is incomplete. This review consolidates contemporary insights into CC pathogenesis and the bioactivity of herbal interventions, highlighting the need for translational research to bridge preclinical findings with clinical applicability. Full article

Background/Objectives: Anorexia–Cachexia Syndrome (ACS) is a multifactorial condition common in advanced chronic illnesses, leading to significant impacts on prognosis and quality of life. This retrospective cohort study aimed to evaluate the prevalence, management strategies, and clinical and patient-centered outcomes of ACS in a home-based palliative care team. Methods: Clinical records of 128 adult patients followed between 2021 and 2024 were analyzed. Data collected included sociodemographic variables, clinical diagnosis, nutritional parameters (Palliative Performance Scale (PPS), Mini Nutritional Assessment (MNA)), symptoms (anorexia, fatigue), interventions (enteral nutrition, psychological and rehabilitative support), and relevant medications. Statistical analysis included descriptive, inferential, and multivariable proportional hazard regression analysis to identify independent predictors of weight loss and anorexia. Results: Manifestations of ACS were observed across both oncologic and non-oncologic conditions. The prevalence of weight loss and anorexia were interrelated and were not different between diagnostic groups. Using multivariable analysis, higher baseline MNA scores (HR = 3.797, p = 0.006) and the use of enteral nutrition (HR = 7.418, p = 0.014) were independently associated with an increased risk of significant weight loss. Lower baseline PPS scores (HR = 0.069), use of enteral nutrition (HR = −0.890), and the presence of psychological support were protective for subsequent anorexia. Dexamethasone use was associated with greater nutritional decline in univariate models. Conclusions: The management of ACS in home palliative care requires the early identification of symptoms, multidisciplinary intervention, and personalized strategies beyond disease etiology. Risk of weight loss is associated with higher MNA scores, and these are best managed in the first week. In anorexia cases, psychological support is protective. Full article

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. This study aimed to compare the two established cachexia definitions (Fearon’s consensus definition and the Global Leadership Initiative on Malnutrition [GLIM] criteria) and their relationships with survival in patients with oesophagogastric cancer. Methods: Consecutive patients newly diagnosed with oesophagogastric cancer (January 2019 to December 2020) were identified from a prospective regional database. Involuntary weight loss, BMI, CT body composition analyses, and neutrophil–lymphocyte ratios were recorded at clinical staging. These data were used to assess patients for cachexia according to Fearon and GLIM diagnostic criteria. The primary outcome of interest was overall survival. Results: Overall, 465 patients (66.9% male, median 71 years) were diagnosed with oesophagogastric cancer during the 2-year study period. Cachectic proportions differed between definitions (Fearon: 59.1% vs. GLIM: 44.1%), and only 49.1% of the 322 patients who met one set of diagnostic criteria were cachectic according to both. Patients who met the GLIM criteria were significantly more comorbid and had a poorer performance status; however, no such difference was evident when using the Fearon definition. Those patients who met either set of diagnostic criteria had shorter survival than those who met neither (p < 0.001). Following adjustment for confounders, GLIM-defined cachexia was more strongly associated with reduced survival (aHR: 1.57 [95% CI: 1.25–1.96], p < 0.001) than Fearon-defined cachexia (aHR: 1.41 [95% CI: 1.13–1.76], p = 0.002). Patients who only met the Fearon diagnostic criteria had prolonged survival (median: 363 days) when compared to those who met only GLIM (median: 158 days) or both definitions (median: 120 days). A secondary analysis of those patients who met the GLIM diagnostic criteria (n = 205) compared the three potential phenotypical criteria used in this definition. Only reduced muscle mass, and not low BMI or weight loss, was associated with poorer survival (aHR: 1.88 [95% CI: 1.15–3.07], p = 0.012) in this group. Conclusions: Cancer cachexia is strongly associated with shortened survival in patients with oesophagogastric cancer. Classification using the GLIM criteria provides more effective prognostication and this definition should be utilised in multidisciplinary patient care. Full article

The experience of bearing witness to the lack of appetite and involuntary weight loss that characterizes cancer anorexia–cachexia syndrome (CACS) is reported to be stressful for family members. Research identifies that family members engage in a wide range of behaviors in response to a relative who shows minimal interest in eating and is literally ‘wasting away’ before their eyes. Some families, though concerned about the symptoms of CACS, do not dwell excessively on the patient’s nutritional intake while others continually harass the patient to eat and petition health care providers for aggressive nutritional interventions to eat in an attempt to stave off further physical deterioration. While studies have detailed how family members respond to a terminally ill relative with CACS, empirical work explicating the explanatory models of CACS that they hold is lacking. Explanatory models (EMs) reflect the beliefs and ideas that families have about why illness and symptoms occur, the extent to which they can be controlled, how they should be treated, and how interventions should be evaluated. To address this gap in the literature, a grounded theory study guided by Kleinman’s Explanatory Model questions was conducted with 25 family members of advanced cancer patients. The core category of ‘Wayfaring’ integrates the key categories of the model and maps onto Kleinman’s questions about CACS onset, etiology, natural course, physiological processes/anatomical structures involved, treatment, and the impacts of disease on patient and family. Findings suggest that a divergence between some biomedical constructions of CACS and explanatory models held by family members may fuel the family–health care provider conflict, thereby providing direction for communication with families about care of the patient with anorexia–cachexia. Full article

Light chain amyloidosis is a plasma–cell disorder with a poor prognosis. It is a progressive condition, causing worsening pain, disability, and life-limiting complications involving multiple organ systems. The medical regimen can be complex, including chemotherapy or immunotherapy for the disease itself, as well as treatment for pain, gastrointestinal and cardiorespiratory symptoms, and various secondary symptoms. Patients and their families must have a realistic awareness of the illness and of the goals and limitations of treatments in making informed decisions about medical therapy, supportive management, and end-of-life planning. Palliative care services can thus improve patients’ quality of life and may even reduce overall treatment costs. Light chain (AL) amyloidosis is a clonal plasma cell disorder characterized by the excessive secretion of light chains by an indolent plasma cell clone that gradually accumulates in vital organs as amyloid fibrils and leads to end-organ damage. With progressive disease, most patients develop diverse clinical symptoms and complications that negatively impact quality of life and increase mortality. Complications include cardiac problems including heart failure, hypotension, pleural effusions, renal involvement including nephrotic syndrome with peripheral edema, gastrointestinal symptoms leading to anorexia and cachexia, complex pain syndromes, and mood disorders. The prognosis of patients with advanced AL amyloidosis is dismal. With such a complex presentation, and high morbidity and mortality rates, there is a critical need for the establishment of a palliative care program in clinical management. This paper provides an evidence-based overview of the integration of palliative care in the clinical management of AL amyloidosis as a means of reducing ER visits, rehospitalizations, and in-hospital mortality. We also discuss potential future collaborative directions in various aspects of clinical care related to AL amyloidosis. Full article

Background: Cancer anorexia-cachexia syndrome (CAS) is a multifactorial condition that is highly prevalent in advanced cancer patients and associated with significant reduction in functional performance, reduction in quality of life, and increased mortality. Currently, no medications are approved for this indication. Recently, the American Society of Clinical Oncology (ASCO) released a rapid recommendation suggesting that low-dose olanzapine once daily may be used to treat cancer cachexia. Many questions still exist on how to use olanzapine for this indication in clinical practice. The objective of this review is to identify existing knowledge on the use of olanzapine for CAS. Methods: A comprehensive search was conducted to identify the primary literature that involved olanzapine for anorexia and cachexia in cancer patients between 2000 and 2023. Results: Seven articles were identified and are discussed here, including two randomized double-blinded placebo-controlled studies, one randomized comparative study, two prospective open-label studies, one retrospective chart review, and one case report. Conclusions: Low dose olanzapine (2.5–5 mg once daily) may be useful in the treatment of CAS for increasing appetite, reducing nausea and vomiting, and promoting weight gain. Further large-scale multi-center randomized placebo-controlled studies will be needed to investigate the impact of olanzapine on weight change in CAS patients. Full article

Cancer cachexia is a complex malnutrition syndrome that causes progressive dysfunction. This syndrome is accompanied by protein and energy losses caused by reduced nutrient intake and the development of metabolic disorders. As many as 80% of patients with advanced cancer develop cancer cachexia; however, an effective targeted treatment remains to be developed. In this study, we developed a novel rat model that mimics the human pathology during cancer cachexia to elucidate the mechanism underlying the onset and progression of this syndrome. We subcutaneously transplanted rats with SLC cells, a rat lung adenocarcinoma cell line, and evaluated the rats’ pathophysiological characteristics. To ensure that our observations were not attributable to simple starvation, we evaluated the characteristics under tube feeding. We observed that SLC-transplanted rats exhibited severe anorexia, weight loss, muscle atrophy, and weakness. Furthermore, they showed obvious signs of cachexia, such as anemia, inflammation, and low serum albumin. The rats also exhibited weight and muscle losses despite sufficient nutrition delivered by tube feeding. Our novel cancer cachexia rat model is a promising tool to elucidate the pathogenesis of cancer cachexia and to conduct further research on the development of treatments and supportive care for patients with this disease. Full article

This study compared mirtazapine with megestrol in the management of cancer-related anorexia–cachexia syndrome in patients with advanced cancer. A randomized, double-blind, controlled clinical trial involving patients with advanced cancer and anorexia–cachexia syndrome was performed. Participants received mirtazapine 30 mg/day or megestrol 320 mg/day for eight weeks. The primary endpoint was the effect of mirtazapine on weight gain and the secondary endpoints were its effect on appetite, muscle strength, physical performance, body composition, adverse events, and medication adherence. Linear regression model with mixed effects was applied and a significance level of 5% was adopted. Fifty-two patients were randomized. Mean age was 65.8 ± 8.4 years. There was weight gain in 52% of the participants in the megestrol group and in 38% in the mirtazapine group after four weeks (p = 0.040). Appetite improved in 92% of the participants in the megestrol group and in 56% in the mirtazapine group after eight weeks (p = 0.007). In the sub-analysis by sex, women showed improvement in appetite (p < 0.001) and weight gain (p < 0.005) in the mirtazapine group, which was not observed in men. Mirtazapine appears to be inferior to megestrol in weight and appetite improvement. However, there may be a difference in the therapeutic response between sexes. Full article

Malnutrition affects up to 75% of cancer patients and results from a combination of anorexia and metabolic dysregulation. Metabolic and nutritional abnormalities in cancer patients can lead to cachexia, a multifactorial syndrome characterized by involuntary loss of skeletal muscle mass, systemic inflammation and increased protein catabolism. Cancer cachexia negatively affects patients’ outcomes, response to anticancer treatments, quality of life, and survival. However, risk of malnutrition, and cachexia are still under-recognized in cancer patients. The Prevalence of Malnutrition in Oncology (PreMiO) study revealed that 51% of patients already had nutritional deficiencies at their first medical oncology visit. Here, we report the results of the subsequent retrospective, observational NUTRItional status at first medical oncology visit ON Clinical Outcomes (NUTRIONCO) study, aimed at assessing the impact of baseline nutritional and non-nutritional variables collected in the PreMiO study on the clinical outcomes of the same patients followed up from August 2019 to October 2021. We have highlighted a statistically significant association between baseline variables and patient death, rehospitalization, and disease progression at follow-up. We found a higher overall survival probability in the well-nourished general study population vs. malnourished patients (p < 0.001). Of major interest is the fact that patient stratification revealed that malnutrition decreased survival probability in non-metastatic patients but not in metastatic patients (p < 0.001). Multivariate analysis confirmed that baseline malnutrition (p = 0.004) and VAS score for appetite loss (p = 0.0104), in addition to albumin < 35 g/L (p < 0.0001) and neutrophil/lymphocyte ratio > 3 (p = 0.0007), were independently associated with the death of non-metastatic patients at follow-up. These findings highlight the importance of proactive, early management of malnutrition and cachexia in cancer patients, and in particular, in non-metastatic patients, from the perspective of a substantial improvement of their clinical outcomes. Full article

Cancer cachexia is a complex multifactorial syndrome whose hallmarks are weight loss due to the wasting of muscle tissue with or without the loss of adipose tissue, anorexia, systemic inflammation, and multi-organ metabolic alterations, which negatively impact patients’ response to anticancer treatments, quality of life, and overall survival. Despite its clinical relevance, cancer cachexia often remains an underestimated complication due to the lack of rigorous diagnostic and therapeutic pathways. A number of studies have shown alterations in gut microbiota diversity and composition in association with cancer cachexia markers and symptoms, thus supporting a central role for dysbiosis in the pathogenesis of this syndrome. Different tools of microbiota manipulation, including probiotics, prebiotics, synbiotics, and fecal microbiota transplantation, have been investigated, demonstrating encouraging improvements in cachexia outcomes. Albeit pioneering, these studies pave the way for future research with the aim of exploring the role of gut microbiota in cancer cachexia more deeply and setting up effective microbiota-targeting interventions to be translated into clinical practice. Full article

Cachexia is a metabolic syndrome consisting of massive loss of muscle mass and function that has a severe impact on the quality of life and survival of cancer patients. Up to 20% of lung cancer patients and up to 80% of pancreatic cancer patients are diagnosed with cachexia, leading to death in 20% of them. The main drivers of cachexia are cytokines such as interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), macrophage inhibitory cytokine 1 (MIC-1/GDF15) and transforming growth factor-beta (TGF-β). Besides its double-edged role as a tumor suppressor and activator, TGF-β causes muscle loss through myostatin-based signaling, involved in the reduction in protein synthesis and enhanced protein degradation. Additionally, TGF-β induces inhibin and activin, causing weight loss and muscle depletion, while MIC-1/GDF15, a member of the TGF-β superfamily, leads to anorexia and so, indirectly, to muscle wasting, acting on the hypothalamus center. Against this background, the blockade of TGF-β is tested as a potential mechanism to revert cachexia, and antibodies against TGF-β reduced weight and muscle loss in murine models of pancreatic cancer. This article reviews the role of the TGF-β pathway and to a minor extent of other molecules including microRNA in cancer onset and progression with a special focus on their involvement in cachexia, to enlighten whether TGF-β and such other players could be potential targets for therapy. Full article

Cachexia is a chronic metabolic syndrome that is characterized by sustained weight and muscle mass loss and anorexia. Cachexia can be secondary to a variety of diseases and affects the prognosis of patients significantly. The increase in inflammatory cytokines in plasma is deeply related to the occurrence of cachexia. As a member of the IL-6 cytokine family, leukemia inhibitory factor (LIF) exerts multiple biological functions. LIF is over-expressed in the cancer cells and stromal cells of various tumors, promoting the malignant development of tumors via the autocrine and paracrine systems. Intriguingly, increasing studies have confirmed that LIF contributes to the progression of cachexia, especially in patients with metastatic tumors. This review combines all of the evidence to summarize the mechanism of LIF-induced cachexia from the following four aspects: (i) LIF and cancer-associated cachexia, (ii) LIF and alterations of adipose tissue in cachexia, (iii) LIF and anorexia nervosa in cachexia, and (iv) LIF and muscle atrophy in cachexia. Considering the complex mechanisms in cachexia, we also focus on the interactions between LIF and other key cytokines in cachexia and existing therapeutics targeting LIF. Full article

Cachexia is a multifactorial and multi-organ syndrome that is a major cause of morbidity and mortality in late-stage chronic diseases. The main clinical features of cancer-related cachexia are chronic inflammation, wasting of skeletal muscle and adipose tissue, insulin resistance, anorexia, and impaired myogenesis. A multimodal treatment has been suggested to approach the multifactorial genesis of cachexia. In this context, physical exercise has been found to have a general effect on maintaining homeostasis in a healthy life, involving multiple organs and their metabolism. The purpose of this review is to present the evidence for the relationship between inflammatory cytokines, skeletal muscle, and fat metabolism and the potential role of exercise training in breaking the vicious circle of this impaired tissue cross-talk. Due to the wide-ranging effects of exercise training, from the body to the behavior and cognition of the individual, it seems to be able to improve the quality of life in this syndrome. Therefore, studying the molecular effects of physical exercise could provide important information about the interactions between organs and the systemic mediators involved in the overall homeostasis of the body. Full article

During its evolution, cancer induces changes in patients’ energy metabolism that strongly affect the overall clinical state and are responsible for cancer-related cachexia syndrome. To better understand the mechanisms underlying cachexia and its metabolic derangements, research efforts should focus on the events that are driven by the immune system activation during the evolution of neoplastic disease and on the phenomena of “resistance” and “tolerance” typically involved in the human body response against stress, pathogens, or cancer. Indeed, in the case where resistance is not able to eliminate the cancer, tolerance mechanisms can utilize the symptoms of cachexia (anemia, anorexia, and fatigue) to counteract unregulated cancer growth. These notions are also sustained by the evidence that cancer cachexia may be reversible if the resistance and tolerance phases are supported by appropriate antineoplastic treatments. Accordingly, there is no doubt that anticachectic therapies have an irreplaceable role in cases of reversible cancer cachexia where, if harmoniously associated with effective antineoplastic therapies, they can contribute to preserve the quality of life and improve prognosis. Such anticachectic treatments should be based on targeting the complex immunological, inflammatory, and metabolic pathways involved in the complex pathogenesis of cachexia. Meanwhile, the role of the anticachectic therapies is very different in the stage of irreversible cachexia when the available antineoplastic treatments are not able to control the disease and the resistance mechanisms fail with the prevalence of the tolerance phenomena. At this stage, they can be useful only to improve the quality of life, allowing the patient and their family to get a better awareness of the final phases of life, thereby opening to the best spiritual remodulation of the final event, death. Full article