W9 Cachexia (GSP)

Question 1

What is the definition of Cachexia?

Answer 1

• A complex metabolic syndrome associated with underlying illness and characterized by loss of muscle with or without loss of fat mass
• Prominent clinical feature
  -weight loss in adults (corrected for fluid retention)
  -growth failure in children (excluding endocrine disorders).

Distinct from:
* Starvation
* Age-related loss of muscle mass
* Primary depression
* Malabsorption
* Hyperthyroidism

• Associated with increased morbidity

Question 2

What is the criteria for cachexia?

Answer 2

Criteria:
* Weight loss > 5% in the past 12 months and underlying chronic disease; or
* BMI < 20, and 3 out of the next 5 criteria:
* decreased muscle strength (lowest tertile);
* fatigue;
* anorexia (↓ food intake);
* low fat-free mass index;
* abnormal biochemistry: increased inflammatory markers CRP (>5.0 mg/L), IL-6 (>4.0 pg/mL); anemia (<12 g/dL); low serum albumin (<3.2 g/dL)

Question 3

Cachexia in ICD-11 (coded MG20) definition:

Answer 3

• A pathological generalised loss of body mass
• with reduction of the storage fat deposits, structural fat and musculature
• that can be accompanied by gradual loss of function of organs

Question 4

Multi-factorial causes of cachexia?

Answer 4

Underlying chronic disease, usually degenerative diseases
* Cancer
* Organ failure: heart, kidney, lung
* HIV/AIDS
* Autoimmune, e.g. rheumatoid arthritis
* Metabolic, e.g. diabetes

Acute events
* Trauma
* Burn
* Acute infection
* → reversed by therapy interventions aimed at the primary cause, although
the signs of cachexia may last longer following recovery

Question 5

Other systemic effects of Cachexia?

Answer 5

Stroma,

Reduced appetite (CNS)
Increased glucocorticoids (Endocrine)
Disrupted sleep pattern (Circadian rhythm)
Metabolic reprogramming (Liver)
Atrophy (Bones)
Altered Microbiome (Gut)
And more..

Question 6

What is the link between anticancer treatment and cachexia?

Answer 6

Synergism of different + simultaneous insults: cancer itself + chemo-induced
* anticancer treatment effective → improvement in cachectic signs + symptoms
* anticancer treatment ineffective → increase catabolism + aggravate cachexia

Question 7

Cancer cachexia
physiological features?

Answer 7

Negative nitrogen balance, negative energy
balance
* Due to reduced food intake, abnormal high metabolism

Question 8

Cancer cachexia
Key feature: skeletal muscle depletion; leads to what? (4)

Answer 8

• reduced antitumor efficacy
• increased chemotherapy toxicity
• complications from cancer surgery
• mortality

Question 9

Management of cachexia - nutrition
what are the steps?

Answer 9

Nutrition support team
* Screen for malnutrition / cachexia, combined with clinical picture
* Screening tests e.g. NRS-2002, MUST, SNAQ, MST
* Customised nutrition recommendations
* Depends on patient’s motivation and convenience
* Goal: improve vs alleviate cachexia
* Ethical discussion on nutritional support

• Dietary prescriptions
• E.g. supplement drinks for HIV, cancer patients
• E.g. supplemental parenteral nutrition

Question 10

Management of cachexia - pharmacological

Answer 10

• Premise: ↑ muscle protein breakdown + ↓ protein synthesis → overall muscle loss
• Potential solution: ramp up muscle production / reduce muscle loss

Question 11

Management of cachexia - pharmacological
what are the main drug classes prescribed? (2)

Answer 11

• Glucocorticoids e.g. prednisolone, methylprednisolone, dexamethasone
• Short term only: 2-3 weeks
• Appetite stimulant, anti-nausea, cancer-related fatigue
• Progestins e.g. medroxyprogesterone, megestrol
• Appetite stimulant, weight improvement
• Risks: thromboembolism, fluid retention, hypogonadism (in males).

Question 12

Management of cachexia - pharmacological
What are some other options?

Answer 12

• Cannabinoids e.g. tetrahydrocannabinol (THC)
• ?Appetite stimulant, data lacking
• Androgens e.g. fluoxymesterone
• Anabolic effects, data lacking
• Olanzapine (atypical antipsychotic)
• Binds to dopamine & serotonin receptors
• Appetite stimulant, anti-nausea, ?weight gain
• NSAIDs e.g. celecoxib, indomethacin, and ibuprofen
• Reduce inflammation by inhibiting prostaglandin production
• ?Weight gain, data lacking
• Immunomodulators e.g. TNF-α inhibitors (infliximab), IL-6 antagonists (ALD518), IL-6R antagonists (tocilizumab)
• ?Appetite stimulant, ?weight gain, data lacking
• Prokinetics e.g. metoclopramide, domperidone
• ?Anti-nausea, data lacking
• Risks: neurological side effects
• Ghrelin receptor agonist e.g. anamorelin
• Appetite stimulant → ↑ muscle mass.
• Not approved in Europe