Cancer cachexia syndrome

1
Cancer cachexia syndrome

• ??.????? ???????
• ??.???? ?????????
• 2/3/50

2
Scope

• Introduction
• Pathogenesis
• Conventional management
• Novel therapy

3
Introduction

• Cachexia Greek word
• Kakos bad
• Hexis condition
• Characteristics
• Weight loss
• Lipolysis
• Muscle wasting
• Anorexia
• Chronic nausea
• Asthenia
• Anemia
• Electrolyte and water abnormalities
• Psychological distress

4
Introduction

• Diagnostic criteria for cachexia
• Unintentional weight loss ( 5)
• BMI
• lt 20 in those aged lt 65 yrs
• lt 22 in those aged 65 yrs
• Albumin lt 3.5 g/dl
• Low fat-free mass (lowest 10)
• Evidence of cytokine excess (eg, elevated
  C-reactive protein)

5
Introduction
6
Introduction

• Cancer cachexia
• 80 of advance disease
• Unclear underlying pathophysiologic mechanism
• Poor prognostic factor
• Differ from other condition
• Starvation
• Dehydration
• Sarcopenia

7
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

8
Introduction
9
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

10
Pathogenesis

• Humeral factor
• TNF-a
• Suppress lipoprotein lipase activity
• Proteolytic activity
• Apoptotis of skeletal muscle
• Increase level of CRH and leptin
• Interleukin-1
• Blocking neuropeptide Y
• Increase level of CRH and leptin

11
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

12
Pathogenesis

• Humeral factor
• Interferon-? (IFN-?)
• Biologic activity overlap with TNF
• Monoclonal Ab against IFN-? could reverse wasting
  syndrome
• Anti-cachetic mediator
• Interleukin-4, interleukin-10, interleukin-13
• Soluble receptor for TNF and IL-6

13
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

14
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

15
Pathogenesis
16
Pathogenesis
17
(No Transcript)
18
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

19
Pathogenesis
20
Pathogenesis

• Protein metabolism
• Increase muscle catabolism
• Decrease muscle protein synthesis
• Muscle wasting asthenia
• Increase tumour protein synthesis
• Increase liver protein synthesis
• Acute phase protein

21
Pathogenesis

• Lipid metabolism
• Increase lipolysis
• Decrease lipogenesis
• Profound loss of adipose tissue
• Decrease lipoprotein lipase
• Decrease clearance of triglyceride
• Hypertriglyceridemia
• Low LDL, HDL

22
Pathogenesis