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Cancer cachexia syndrome
นพ.บูรพา ปุสธรรม นพ.มณฑล ว่องวัณดี 2/3/50
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Scope Introduction Pathogenesis Conventional management Novel therapy
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Introduction Cachexia : Greek word Characteristics Kakos : bad
Hexis : condition Characteristics Weight loss Lipolysis Muscle wasting Anorexia Chronic nausea Asthenia Anemia Electrolyte and water abnormalities Psychological distress
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Introduction Diagnostic criteria for cachexia
Unintentional weight loss (≥ 5%) BMI < 20 in those aged < 65 yrs < 22 in those aged ≥ 65 yrs Albumin < 3.5 g/dl Low fat-free mass (lowest 10%) Evidence of cytokine excess (eg, elevated C-reactive protein)
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Introduction
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Introduction Cancer cachexia 80 % of advance disease
Unclear underlying pathophysiologic mechanism Poor prognostic factor Differ from other condition Starvation Dehydration Sarcopenia
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Introduction Cachexia VS anorexia (starvation) Body composition
Cachexia : loss of fat and skeletal muscle prior decrease food intake, reserve non-muscle protein Anorexia : loss of fat but small amount of muscle, after decrease food intake Weight loss Cachexia : complex metabolic events Anorexia : simple nutritional deficiency Treatment Cachexia : multiple aspect Anorexia : treatable by protein-calorie supplementation
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Introduction
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Introduction Factors contributing for cancer cachexia Host-related
Humeral factors Treatment factors Chemotherapy : mucositis, nausea, vomitting, diarrhea, taste alteration Radiotherapy : enteritis, diarrhea, decrease saliva Surgery : malabsortion due to gactrectomy, short bowel syndrome, pancreatic resection Tumour-related Tumour mediator Mechanical problem GI tract malignancy
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Pathogenesis Humeral factor TNF-α Interleukin-1
Suppress lipoprotein lipase activity Proteolytic activity Apoptotis of skeletal muscle Increase level of CRH and leptin Interleukin-1 Blocking neuropeptide Y
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Pathogenesis Humeral factor Interleukin-6
Activation of ubiquitin ligase-dependent preteosome pathway Leukemia inhibitor factor (LIF) Increase leptin Ciliary neurotropic factor Compose from IL-6 and LIF Potent cachectic effect Acute-phase protein response
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Pathogenesis Humeral factor Interferon-γ (IFN-γ)
Biologic activity overlap with TNF Monoclonal Ab against IFN-γ could reverse wasting syndrome Anti-cachetic mediator Interleukin-4, interleukin-10, interleukin-13 Soluble receptor for TNF and IL-6
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Pathogenesis Tumour mediator Lipid mobilizing factor(LMF)
Induce lipolysis Correlate with weight loss Proteolysis inducing factor(PIF) Induce protein degradation Decrease protein systhesis May increase cytokines and acute phase protein
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Pathogenesis Tumour mediator Anemia inducing substance(AIS)
Decrease osmotic resistance and deformability Increase fragile Alter energy metabolism Tumour product? Induce uncoupling protein(UPC) UPC 3 : brown adipose tissue and skeletal muscle Decrease ATP production Increase heat production
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Pathogenesis
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Pathogenesis
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Pathogenesis Glucose homeostasis Increase gluconeogenesis
Muscle and fat breakdown Increase glycolysis from muscle and tumour Increase lactate production Elevation of cori cycle activity 300 kcal/day of energy loss Glucose intolerance Insulin resistance Increase counter regulatory hormone Decrease muscle glucose uptake
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Pathogenesis
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Pathogenesis Protein metabolism Increase muscle catabolism
Decrease muscle protein synthesis Muscle wasting : asthenia Increase tumour protein synthesis Increase liver protein synthesis Acute phase protein
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Pathogenesis Lipid metabolism Increase lipolysis Decrease lipogenesis
Profound loss of adipose tissue Decrease lipoprotein lipase Decrease clearance of triglyceride Hypertriglyceridemia Low LDL, HDL
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Pathogenesis
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