Exploring the therapeutic effect of Xiaoyan d ecoction on lung cancer cachexia skeletal muscle atrophy based on L3-SMI

Background:Lung cancer cachexia has received widespread attention as one of the most common complications in patients with advanced lung cancer.As a multifactorial syndrome,lung cancer cachexia is characterized by a persistent decline in muscle mass that cannot be reversed by conventional nutrition Xiaoyan d ecoction can promote appetite and improve skeletal muscle mass in patients with lung cancer cachexia,while the third lumbar skeletal muscle index(L3-SMI)is able to determine whole-body skeletal muscle mass.To analyze the relationship between L3-SMI and hematological indexes and lung cancer cachexia,and to study the clinical efficacy of Xiaoyan decoction on skeletal muscle atrophy in lung cancer cachexia patients,with the aim of providing a reference basis for the early diagnosis and treatment of lung cancer cachexia patients and skeletal muscle atrophy.Methods:148 patients who were diagnosed with lung cancer in the Department of Oncology of the First Affiliated Hospital of Tianjin University of Traditional Chinese Medicine from January 2020 to December 2022 were included,and were divided into cachexia and non-cachexia groups according to the diagnostic criteria of cachexia,and analyzed the differences of hematological indexes and L3-SMI between cachexia patients and non-cachexia patients.And the patients with cachexia were divided into control group and treatment group,analyzed and compared the changes of body mass index(BMI),L 3-SMI,Karnofsky functional status score,albumin and other hematological indexes of the two groups before and after the treatment,and evaluated the safety of the Xiaoyan decoction in the treatment of cachexia.Results:A total of 148 lung cancer patients were included in this study,including 67 patients in the cachexia group and 81 patients in the non-cachexia group.According to the pre-treatment statistical analysis,the BMI of patients in the cachexia group was lower than that of patients in the non-cachexia group(P<0.05);among the biochemical function indexes,the proportions of creatinine(P<0.05),total protein(P<0.05),The levels of albumin in the cachexia group were significantly lower(P<0.05)compared to the non-cachexia group;in the cachexia group,both males and females had lower L3-SMIs than in the non-cachexia group(P<0.05).A total of 62 cases of lung cancer cachexia were studied,30 cases in the control group and 32 cases in the treatment group,according to statistical analysis,BMI was significantly different before and after treatment(P<0.05);L3-SMI was significantly different in the treatment group before and after treatment(P<0.05);Karnofsky significantly differed in the treatment group before and after treatment(P<0.05);and there was a significant difference in albumin before and after(P<0.05).Conclusion:Cachexia patients had significantly lower third lumbar skeletal muscle mass than non-cachexia patients,according to this study;Xiaoyan decoction was able to improve skeletal muscle mass,nutritional status as well as functional status of patients with cachexia in lung cancer,among others.

Treatment of cancer cachexia with exercise

Cancer cachexia is a multifactorial syndrome characterized by the irreversible loss of body weight,fat,and muscle.Its main characteristics include nutrient intake and absorption disorders,systemic inflammation,mitochondrial dysfunction,immune imbalance,and protein and fat consumption,which ultimately lead to patient death.So far,there has been no effective method identified to combat the malignant progression of cancer cachexia.The effects of a single nutritional supplement or drug intervention strategy are insufficient.Exercise training is considered a potential treatment for cancer cachexia.Both clinical studies and animal experiments suggest that exercise training can help improve the intake and absorption of nutrients,inhibit inflammatory signaling pathways,regulate immunity andmetabolism,alleviate insulin resistance,promote protein synthesis,maintain muscle mass,and so on.The use of multimodal methods that combine nutritional support and/or other treatments with exercise provides a potential prospect for the treatment of cancer cachexia.However,the optimal prescription of exercise for the treatment of cancer cachexia is still unclear.The main purpose of this review is to summarize the growing body of research on the impact of exercise on cancer cachexia and to provide evidence supporting the use of exercise as an intervention for cancer cachexia in the clinical setting.

Study on possible synergistic anticancer cachexia effects of the main active compounds of Radix Sophorae flavescentis

Background:Cancer cachexia is a complex disease secondary to cancer,and no specific therapy for it has been found.The Chinese herb Kushen(Radix Sophorae flavescentis)is the dried root of Sophora flavescens Aiton,which has been widely applied in treating digestive and urinary inflammatory diseases.Matrine,one of the main components of Radix Sophorae flavescentis,can alleviate cancer cachexia.Methods:Compounds from Radix Sophorae flavescentis were screened using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform.The targets related to cancer cachexia were queried from the Therapeutic Target Database(http://db.idrblab.net),DisGeNET database(http://www.disgenet.org),and Search Tool for Interacting Chemicals database,related literature,and constructed cancer cachexia-protein network.Cancer cachexia-protein network was merged with compound-protein networks respectively using Cytoscape software as well as network topology data and key targets counting.Pathway enrichment analysis was conducted via the Database for Functional Annotation Bioinformatics Microarray Analysis.Protein crystal structures and compound structures were queried from RCSB and PubChem databases,respectively.Molecular docking was conducted using Discovery Studio software.Results:The anticancer cachexia compounds of Radix Sophorae flavescentis were screened as oxymatrine,matrine,and kurarinol,and targets such as BIRC2,TNF and STAT3 were found.The mechanisms of oxymatrine,matrine,and kurarinol have the characteristics of synergy and complementarity.Kurarinol has a mechanism similar to that of matrine,which includes the FoxO signaling pathway,insulin resistance and mTOR signaling pathway.TNF signaling pathway is a common signaling pathway of kurarinol,oxymatrine and matrine.Adipocytokine signaling pathway is the other common pathway of kurarinol and oxymatrine except for the TNF signaling pathway.Kurarinol can be successfully docked with CYCS,GPX2,BIRC7,etc.,and kushenol C can be successfully docked with IKBKB and PIK3CD.Conclusion:Kurarinol,matrine,oxymatrine,and kushenol C may be the key compounds of Radix Sophorae flavescentis treating cancer cachexia.Additionally,TNF signaling pathway is the key pathway for the synergistic action of kurarinol,matrine and oxymatrine.

Research progress on pathogenesis and related pathways of Cancer cachexia

Cancer cachexia is a complex syndrome of metabolic changes caused by many factors in tumor patients,which characterized by emaciation,weight loss,muscle atrophy,anemia and hypoproteinemia,it's seriously affects the quality of life,cycle and therapeutic effect of patients.At present,there is no curative effect in the treatment of cancer cachexia,because the pathogenesis is still unclear.So it is particularly important to study the pathogenesis,mechanism and related pathway of cancer cachexia.In this paper,the definition,stage and diagnosis of cachexia,traditional Chinese medicine theoretical research,related anorexia mechanism,protein decomposition mechanism,fat decomposition mechanism,sugar metabolism mechanism,inflammatory factor mechanism and other aspects were analyzed and summarized to provide theoretical basis for the study of cachexia pathogenesis and clinical application selection.

Nutritional support strategies for cancer cachexia

Tumor cachexia is widely seen in patients with various stages of cancer,manifested by inadequate intake or abnormal hypermetabolism resultingin negative nitrogen and energy balance. Early intervention of nutritionaltherapy and penetrate it into other anti-cancer treatment processes cansignificantly benefit cancer patients who receiving palliative treatment.Nutritional therapy for cancer is a process of planning, implementing, evaluatingand nutritional intervention to treat cancer and its complications orphysical condition, to improve the prognosis of cancer patients, includingnutritional diagnosis (screening/evaluation), nutritional intervention, efficacyevaluation (including follow-up) three stages. In practice, we shouldchoose appropriate nutritional risk assessment tools and interventionmethods according to the actual situation of patients, avoid over-treatment,reduce complications, and maximize patients'interests as far as possible.Nutritional support therapy for cancer involves ethics, morality and thewishes of patients and their families, and needs further exploration andimprovement. The best nutritional support strategy often requires the jointparticipation of many disciplines, including clinicians, nurses, nutritionistsand psychosocial workers. Nutritional support group and multidisciplinarycollaboration group on cancer are gradually becoming a trend. With theaccumulation of experience in cancer nutrition therapy, the developmentand application of drugs and nutritional preparations, and the deepening ofmulti-disciplinary collaboration, more cancer patients will benefit in clinicalwork.

Cancer cachexia,mechanism and treatment

It is estimated that half of all patients with cancer eventually develop a syndrome of cachexia, with anorexia and a progressive loss of adipose tissue and skeletal muscle mass. Cancer cachexia is characterized by systemic inflammation, negative protein and energy balance, and an involuntary loss of lean body mass. It is an insidious syndrome that not only has a dramatic impact on patient quality of life, but also is associated with poor responsesto chemotherapy and decreased survival. Cachexia is still largely an underestimated and untreated condition, despite the fact that multiple mechanisms are reported to be involved in its development, with a number of cytokines postulated to play a role in the etiology of the persistent catabolic state. Existing therapies for cachexia, including orexigenic appetite stimulants, focus on palliation of symptoms and reduction of the distress of patients and families rather than prolongation of life. Recent therapies for the cachectic syndrome involve a multidisciplinary approach. Combination therapy with diet modification and/or exercise has been added to novel pharmaceutical agents, such as Megestrol acetate, medroxyprogesterone, ghrelin, omega-3-fatty acid among others. These agents are reported to have improved survival rates as well as quality of life. In this review, we will discuss the emerging understanding of the mechanisms of cancer cachexia, the current treatment options including multidisciplinary combination therapies, as well an update on new and ongoing clinical trials.

The rationale for preventing cancer cachexia：targeting excessive fatty acid oxidation

Cachexia commonly occurs at the terminal stage of cancer and has largely unclear molecular mechanisms.A recent study published in Nature Medicine,entitled "Excessive fatty acid oxidation induces muscle atrophy in cancer cachexia," reveals that cachectic cancer cells can secrete multiple cytokines that induce excessive fatty acid oxidation,which is responsible for muscle loss in cancer cachexia.Inhibition of fatty acid oxidation using etomoxir can increase muscle mass and body weight in cancer cachexia animal models.The usage of stable cachexia animal models is also discussed in this research highlight.

Cancer cachexia:Focus on cachexia factors and inter-organ communication

Cancer cachexia is a multi-organ syndrome and closely related to changes in signal communication between organs,which is mediated by cancer cachexia factors.Cancer cachexia factors,being the general name of inflammatory factors,circulating proteins,metabolites,and microRNA secreted by tumor or host cells,play a role in secretory or other organs and mediate complex signal communication between organs during cancer cachexia.Cancer cachexia factors are also a potential target for the diagnosis and treatment.The pathogenesis of cachexia is unclear and no clear effective treatment is available.Thus,the treatment of cancer cachexia from the perspective of the tumor ecosystem rather than from the perspective of a single molecule and a single organ is urgently needed.From the point of signal communication between organs mediated by cancer cachexia factors,finding a deeper understanding of the pathogenesis,diagnosis,and treatment of cancer cachexia is of great significance to improve the level of diagnosis and treatment.This review begins with cancer cachexia factors released during the interaction between tumor and host cells,and provides a comprehensive summary of the pathogenesis,diagnosis,and treatment for cancer cachexia,along with a particular sight on multi-organ signal communication mediated by cancer cachexia factors.This summary aims to deepen medical community’s understanding of cancer cachexia and may conduce to the discovery of new diagnostic and therapeutic targets for cancer cachexia.

A comprehensive review of animal models for cancer cachexia:Implications for translational research

Cancer cachexia is a multifactorial syndrome characterized by progressive weight loss and a disease process that nutritional support cannot reverse.Although progress has been made in preclinical research,there is still a long way to go in translating research findings into clinical practice.One of the main reasons for this is that existing preclinical models do not fully replicate the conditions seen in clinical patients.Therefore,it is important to understand the characteristics of existing preclinical models of cancer cachexia and pay close attention to the latest developments in preclinical models.The main models of cancer cachexia used in current research are allogeneic and xenograft models,genetically engineered mouse models,chemo-therapy drug-induced models,Chinese medicine spleen deficiency models,zebrafish and Drosophila models,and cellular models.This review aims to revisit and summarize the commonly used animal models of cancer cachexia by evaluating existing preclinical models,to provide tools and support for translational medicine research.

Jianpi Decoction Combined with Medroxyprogesterone Acetate Alleviates Cancer Cachexia and Prevents Muscle Atrophy by Directly Inhibiting E3 Ubiquitin Ligase

ObjectiveTo provide comprehensive evidence for the anti-cancer cachexia effect of Jianpi Decoction(JP)and to explore its mechanism of anti-cancer cachexia.MethodsA mouse model of colon cancer(CT26)-induced cancer cachexia(CC)was used to investigate the anti-CC effect of JP combined with medroxyprogesterone acetate(MPA).Thirty-six mice were equally divided into 6 groups:normal control,CC,MPA(100 mg·kg^(−1)·d^(−1)),MPA+low-dose(20 mg·kg^(−1)·d^(−1))JP(L-JP),MPA+medium-dose(30 mg·kg^(−1)·d^(−1))JP(M-JP),and MPA+high-dose(40 mg·kg^(−1)·d^(−1))JP(H-JP)groups.After successful modeling,the mice were administered by gavage for 11 d.The body weight and tumor volume were measured and recorded every 2 d starting on the 8th day after implantation.The liver,heart,spleen,lung,kidney,tumor and gastrocnemius muscle of mice were collected and weighed.The pathological changes of the tumor was observed,and the cross-sectional area of the gastrocnemius muscle was calculated.The protein expressions of STAT3 and E3 ubiquitinase in the gastrocnemius muscle were measured by Western blot.In addition,an in vitro C2C12 myotube formation model was established to investigate the role of JP in hindering dexamethasone-induced muscle atrophy.In vitro experiments were divided into control,model,and JP serum groups.After 2-d administration,microscopic photographs were taken and myotube diameters were calculated.Western blot was performed to measure the protein expressions of STAT3 and E3 ubiquitinase.ResultsJP combined with MPA restored tumor-induced weight loss(P<0.05,vs.CC)and muscle fiber size(P<0.01,vs.CC).Mechanistically,JP reduced the expression of atrophy-related proteins MuRF1 and MAFbx in tumor-induced muscle atrophy in vivo(P<0.05,vs.CC).In addition,JP reduced the expression of atrophy-related proteins MuRF1 and MAFbx and p-STAT3 phosphorylation(P<0.05 or P<0.01 vs.model group)in C2C12 myotubes treated with dexamethasone in vitro.ConclusionsAdministration of JP combined with MPA restores tumor-induced cachexia conditions.In addition,the profound effect of JP combined with MPA on tumor-induced cachexia may be due to its inhibition of muscle proteolysis(E3 ubiquitinase system).

Role of brown adipose tissue in metabolic syndrome, aging, and cancer cachexia

Brown adipose tissue （BAT） plays a fundamental role in maintaining body temperature by producing heat. BAT that had been know to exist only in mammals and the human neonate has received great attention for the treatment of obesity and diabetes due to its important function in energy metabolism, ever since it is recently reported that human adults have functional BAT. In addition, beige adipocytes, brown adipocytes in white adipose tissue （WAT）, have also been shown to take part in whole body metabolism. Multiple lines of evidence demonstrated that transplantation or activation of BAT or/and beige adipocytes reversed obesity and improved insulin sensitivity. Furthermore, many genes involved in BAT activation and/or the recruitment of beige cells have been found, thereby providing new promising strategies for future clinical application of BAT activation to treat obesity and metabolic diseases. This review focuses on recent advances of BAT function in the metabolic aspect and the relationship between BAT and cancer cachexia, a pathological process accompanied with decreased body weight and increased energy expenditure in cancer patients. The underlying possible mechanisms to reduce BAT mass and its activity in the elderly are also discussed.

The mechanism by which noncoding RNAs regulate muscle wasting in cancer cachexia

Cancer cachexia(CC)is a complex metabolic syndrome that accelerates muscle wasting and affects up to 80%of patients with cancer;however,timely diagnostic methods and effective cures are lacking.Although a considerable number of studies have focused on the mechanism of CC-induced muscle atrophy,few novel therapies have been applied in the last decade.In recent years,noncoding RNAs(ncRNAs)have attracted great attention as many differentially expressed ncRNAs in cancer cachectic muscles have been reported to participate in the inhibition of myogenesis and activation of proteolysis.In addition,extracellular vesicles(EVs),which function as ncRNA carriers in intercellular communication,are closely involved in changing ncRNA expression profiles in muscle and promoting the development of muscle wasting;thus,EV-related ncRNAs may represent potential therapeutic targets.This review comprehensively describes the process of ncRNA transmission through EVs and summarizes the pathways and targets of ncRNAs that lead to CC-induced muscle atrophy.

Pathological features of tissues and cell populations during cancer cachexia

Cancers remain among the most devastating diseases in the human population in spite of considerable advances in limiting their impact on lifespan and healthspan.The multifactorial nature of cancers,as well as the number of tissues and organs that are affected,have exposed a considerable diversity in mechanistic features that are reflected in the wide array of therapeutic strategies that have been adopted.Cachexia is manifested in a number of diseases ranging from cancers to diabetes and ageing.In the context of cancers,a majority of patients experience cachexia and succumb to death due to the indirect effects of tumorigenesis that drain the energy reserves of different organs.Considerable information is available on the pathophysiological features of cancer cachexia,however limited knowledge has been acquired on the resident stem cell populations,and their function in the context of these diseases.Here we review current knowledge on cancer cachexia and focus on how tissues and their resident stem and progenitor cell populations are individually affected.

The immunological regulation of cancer cachexia and its therapeutic implications

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-g, participate in the syndrome of cachexia. Yet therapeutic targeting of these pro-inflammatory factors has not yielded meaningful improvements in cachexia management. More recently, the impact of immune cells in the tumour mass (tumour-associated macrophages) and host circulation (myeloid suppressor cells) has garnered much interest with regards to their role in immune tolerance in cancer. However, their role in the generation of systemic inflammation and cancer cachexia is underexplored and outstanding questions remain. This review summarises the key mediators and targets of immune dysfunction in cancer cachexia. Here we describe the host response including skeletal muscle wasting;highlight the current knowledge gap areas;and report the results of previously trialled immunotherapies. A greater understanding of complex interaction between the tumour, immune system and peripheral tissues in the genesis and maintenance of cancer cachexia is a key step in n identifying future therapeutic targets.

Molecular therapeutic strategies targeting pancreatic cancer induced cachexia

Pancreatic cancer(PC) induced cachexia is a complex metabolic syndrome associated with significantly increased morbidity and mortality and reduced quality of life. The pathophysiology of cachexia is complex and poorly understood. Many molecular signaling pathways are involved in PC and cachexia. Though our understanding of cancer cachexia is growing, therapeutic options remain limited. Thus, further discovery and investigation of the molecular signaling pathways involved in the pathophysiology of cachexia can be applied to development of targeted therapies. This review focuses on three main pathophysiologic processes implicated in the development and progression of cachexia in PC, as well as their utility in the discovery of novel targeted therapies. Skeletal muscle wasting is the most prominent pathophysiologic anomaly in cachectic patients and driven by multiple regulatory pathways. Several known molecular pathways that mediate muscle wasting and cachexia include transforming growth factor-beta(TGF-β), myostatin and activin, IGF-1/PI3 K/AKT, and JAK-STAT signaling. TGF-β antagonism in cachectic mice reduces skeletal muscle catabolism and weight loss, while improving overall survival. Myostatin/activin inhibition has a great therapeutic potential since it plays an essential role in skeletal muscle regulation. Overexpression of insulin-like growth factor binding protein-3(IGFBP-3) leads to increased ubiquitination associated proteolysis, inhibition of myogenesis, and decreased muscle mass in PC induced cachexia. IGFBP-3 antagonism alleviates muscle cell wasting.Another component of cachexia is profound systemic inflammation driven by pro-cachectic cytokines such as interleukin-6(IL-6), tumor necrosis factoralpha(TNF-α), and interferon gamma(INF-γ). IL-6 antagonism has been shown to reduce inflammation, reduce skeletal muscle loss, and ameliorate cachexia. While TNF-α inhibitors are clinically available, blocking TNF-α signaling is not effective in the treatment of cancer cachexia. Blocking the synthesis or action of acute phase reactants and cytokines is a feasible therapeutic strategy, but no anti-cytokine therapies are currently approved for use in PC. Metabolic alterations such as increased energy expenditure and gluconeogenesis, insulin resistance, fat tissue browning, excessive oxidative stress, and proteolysis with amino acid mobilization support tumor growth and the development of cachexia. Current innovative nutritional strategies for cachexia management include ketogenic diet, utilization of natural compounds such as silibinin, and supplementation with ω3-polyunsaturated fatty acids. Elevated ketone bodies exhibit an anticancer and anticachectic effect. Silibinin has been shown to inhibit growth of PC cells, induce metabolic alterations, and reduce myofiber degradation. Consumption of ω3-polyunsaturated fatty acids has been shown to significantly decrease resting energy expenditure and regulate metabolic dysfunction.

Managing Cachexia and Improving Quality of Life in Cancer Patients Using Novel Nutritional Supplements: A PAN India Study

Cancer patients develop cachexia due to systemic inflammation, negative protein and energy balance. Esperer Onco Nutrition (EON) has come up with innovative nutritional supplements (EON Therapy) that help patients take the rigours of cancer therapy thereby improving prognosis and Quality of Life (QoL). This Post-marketing surveillance study was undertaken on 38 volunteers to assess the impact of EON therapy on cachexia and QoL of patients undergoing curative treatment. Body weight and biochemical parameters of the volunteers were recorded at each visit. Volunteers were assessed using ECOG Scale and Malnutrition Screening Tool (MST) to assess impact of nutritional supplements on QoL. Weight loss was observed in most of the patients for first two visits but the patients gained weight over subsequent visits and average weight at end of the study was higher than initial weight. At the end of study 22 of 38 volunteers gained weight and 7 volunteers maintained initial weight. The biochemical parameters either showed improvement or remained same. The QoL analysis indicated a marked improvement in physical wellness and nutritional status and no adverse effects were reported. In conclusion, the study underlines importance of research based on nutritional supplements for cancer patients for better disease management and prognosis.

Cancer, Malnutrition and Cachexia: We Must Break the Triad

Many factors can modify nutritional status in cancer patients, including cachexia, nausea and vomiting, decreased caloric intake or oncologic treatments causing malabsorption. The cachexia-anorexia syndrome is a complex metabolic syndrome associated with cancer and some other palliative conditions characterized by involuntary weight loss involving fat and muscle, anorexia, early satiety, fatigue and weakness due to shifts in metabolism caused by tumour by-products and cytokines. Cachexia is a distressing and debilitating condition, affecting significant numbers of patients with advanced disease and is the primary cause of death in about 20% of all patients with cancer. Though cachexia is most commonly associated with particular tumours, such as head and neck, gastrointestinal tract, pancreas, central nervous system and lung, it may affect any patient with any tumour at any site;no patient and no tumour are excluded. Current treatment for principally depends on its prevention rather than reversing the present disease state, and the clinical results are far from being satisfactory. A careful decision based on good clinical judgement is necessary before deciding to start either enteral or parenteral nutrition, to avoid a useless, costly and difficult treatment. Treatment should be directed toward improvement in the quality of life of the patient and should often include nutritional counseling. It should take into consideration both disease and treatment related factors as well as the cachexia syndrome itself.

EON Therapy Ameliorates Cachexia and Quality of Life in Cancer Patients

Cancer induced cachexia, a gross loss of skeletal muscle with or without adipose tissue wasting, remains a clinical impasse resulting in poor prognosis and Quality of Life (QoL). It is characterized by an inflammation driven anorexia and aberrant energy and protein balance. Indubitably, nutritional rehabilitation is required to address various daunting challenges of this multifactorial syndrome. Esperer Onco Nutrition has come up with an optimal clinical nutrition formulation with promising anti-cachexia effects. Towards validating the efficacy and ensuring the safety of EON Therapy (Es-Invigour plus Es-Fortitude-Protect) under clinical settings, a phase IV post marketing surveillance (PMS) study with 63 patients from various hospitals across India was undertaken. This multi-nutrient and multi-targeted nutritional intervention, being concurrent with mainstream therapy, demonstrated potential to ameliorate the cachectic condition which was measured by body weight of the volunteers at each visit. Biochemical parameters improved or remained same. Overall QoL assessment was performed by using ECOG Scale and Malnutrition Screening Tool (MST) which showed significant improvement in physical wellness and nutritional status of the volunteers. No adverse effect was observed during the entire period. These observations reinforce the need of research based nutritional intervention for clinical use in cachectic cancer patients.

Health Related Quality of Life and Biochemical Markers for Cachexia Evaluation in Head and Neck Cancer Patients

Cachexia is a multifactorial syndrome related to unintentional weight loss and to loss of muscle and fat mass. In head and neck cancer (HNC) its incidence is important and not only related to a deficient intake of food due to the impact of the disease in the vital functions. A complex disturbance in the normal metabolism of the patient promotes a persistent inflammatory state and a shifting in the metabolism balance toward a catabolic predominance affecting primarily the skeletal muscle. This leads to severe impairment of the functional, emotional and social status and quality of life of the patients that will compromise response to treatment and the disease prognosis. Understanding this deleterious syndrome and mainly identifying it in early stages of the disease is of a major importance in achieving better outcomes to head and neck cancer patients. This study pretends to identify clinical aspects related to cachexia in HNC in a clinical perspective for application on the routine clinical practice. In our study, 30 HNC patients were enrolled and evaluated in terms of nutritional values (actual and loss of weight in the past 6 months, body mass index (BMI), nutritional risk index (NRI), malnutrition universal screening tool), serum biochemical markers (albumin, total proteins, cholesterol, triglycerides, urea, C-reactive protein (CRP), interleukin-6 (IL-6), tumour necrosis factor-α (TNF-α) and myostatin) and health related quality of life (HRQoL) evaluation (using European Organisation for the Research and Treatment of Cancer (EORTC) quality of life questionnaires (QLQ): EORTC QLQ-C30 and EORTC QLQ-HN43). A minimum follow-up of 48 months was considered for all patients. Our results showed that NRI is a good and sensitive index to identify cachexia. This index uses two parameters, one constitutional (loss of weight) and one biochemical (level of serum albumin). According to this criterion, 16 patients were assigned to the No-cachexia group and 14 patients to the Cachexia group. Significant differences in the constitutional and nutritional values between the two groups were found: the median weight loss was 4.44 kg in the No-cachexia group and 11.29 kg in the Cachexia group, while the BMI was 21.88 and 18.33, respectively. In terms of biochemical markers, significant low values of albumin and cholesterol in the Cachexia group were encountered when compared to the No-cachexia group. Regarding the inflammatory and cachexia biomarkers studied, the results show that patients in the Cachexia group had significantly higher levels of CRP and of the proinflammatory cytokines IL-6 and TNF-α and presented significantly raised levels of the myostatin. In terms of HRQoL evaluation, the scores of the EORTC QLQ-C30 revealed that all the scales and the Summary Score showed lower scores in the Cachexia group, indicating worst quality of life evaluation. The items scores were globally higher in the Cachexia group indicating more important problems related to those items in the Cachexia group. The difference encountered between the groups was significant (p < 0.001) in all considered scales but two: Dyspnoea and Constipation. Considering the EORTC QLQ-HN43 all the scales and in all single items but one (Wound Healing) the scores were higher in the Cachexia group, indicating a worst degree of problems affecting these group of patients. The difference found between the groups was significant (p < 0.001) in all scales and items but six: Dry Mouth and Sticky Saliva, Skin problems, Problems with Teeth, Trismus, Social Contact and Wound Healing. There were no significant differences in the clinical presentation of the disease between the two groups. The median survival was of 13.5 months in the Cachexia group, significantly lower when compared to the No-cachexia group (p < 0.0001), confirming the major impact of cachexia in survival and clinical outcomes in HNC patients. These results of our study show that HRQoL evaluation and serum biochemical markers are sensitive and important tools in identifying and screening cachexia in HNC patients. The methodology followed in this study correlating HRQoL with biochemical markers supports the development of clinical protocols in HNC that include cachexia evaluation. Hopefully this new approach can help to improve prognosis of the disease.

基于“脾主肌肉”论健脾法在肿瘤恶病质肌肉萎缩中的应用

肌肉萎缩是肿瘤恶病质晚期患者中最易出现的症状,也是肿瘤患者预后不良的一个危险征兆,临床常用食欲刺激药、营养神经肌肉药物等手段并不能逆转肿瘤恶病质肌肉萎缩。肿瘤恶病质肌肉萎缩的临床特征与中医“虚劳”相似,其发生的病因病机多为脾摄乏源、运动减少、忧思伤脾、毒邪结聚、气血暗耗、脏腑虚衰等,最终导致脉络阻塞、气血亏空,从而肌肉失于濡养出现肌肉萎缩。肿瘤恶病质肌肉萎缩的发生究其根本是中焦脾土运化失司,水谷精微化生不足,气血乏源难以充养肌肉出现肌肉萎缩。中医药在治疗肿瘤恶病质肌肉萎缩方面也越来越凸显出巨大优势,综合近数十年关于肿瘤恶病质肌肉萎缩的研究发现,中医治则大多从健脾和胃、健脾益肾、健脾解毒、健脾疏肝入手,健脾法始终贯穿着其治疗的根本核心。脾主运化与气血的生成、肌肉的充实密切相关,脾失健运导致肌肉萎缩的提法最早可见于《黄帝内经》,因此基于“脾主肌肉”理论,结合中医整体观来探讨健脾法治疗肿瘤恶病质肌肉萎缩的中医机理,以期为临床治疗提供新的诊疗思路。