Cachexia (physical wasting associated with long-term illness)



OVERVIEW

Definition

Cachexia, also known as cachexia, is a malnutritional disorder associated with chronic disease, often accompanied by nonspecific inflammation, and is a specific form of malnutrition.

The more accepted definition of cachexia is a multifactorial syndrome characterized by persistent skeletal muscle wasting, with or without loss of adipose tissue, which is not fully relieved by conventional nutritional therapy and can eventually lead to progressive functional impairment [1].

Malignant disease is often associated with a variety of chronic conditions, including malignancy, chronic obstructive pulmonary disease, chronic heart failure, chronic renal failure, hepatic insufficiency, AIDS, and rheumatoid arthritis.

Malignant disease often occurs in patients with progressive malignant tumors, but can also be seen in patients with early malignant tumors.

[Read Hint] The malignant stroma mentioned in this entry is mainly based on tumor malignant stroma.

Classification

According to the etiology, tumor malignant stroma can be divided into two categories:

Primary malignant stroma: directly caused by the malignant tumor itself.

Secondary malignant stroma: caused by malnutrition or underlying disease.

Morbidity

Malignant stroma is a common complication of various advanced malignant tumors.

Some reports show that malignant stroma may occur in 60% to 80% of tumor patients, among which the most frequently occurring malignant stroma tumors are lung cancer and digestive system tumors.

Causes

Causes

Tumor

Long-term tumor diseases, especially the middle and late stages of malignant tumors, are prone to malignant stroma.

Other chronic wasting diseases

Chronic obstructive pulmonary disease, chronic heart failure, chronic renal failure, hepatic insufficiency, AIDS and rheumatoid arthritis.

Pathogenesis

The development of tumor malignancy involves a variety of factors, including anorexia nervosa, decreased physical activity, decreased secretion of host synthetic hormones, and abnormalities in protein, lipid, and carbohydrate metabolism.

It is currently believed that cytokine-mediated inflammation and abnormalities in body metabolism are closely related to the development of cancer cachexia.

Overexpression of tumor-associated genes leads to an increase in mediators that cause catabolism, while cancer-induced inflammation can produce pro-inflammatory cytokines.

The main features of metabolic abnormalities in patients with tumor malignancy include increased energy expenditure, increased protein and/or lipolysis, and decreased protein synthesis.

The main mechanisms may involve include neuro-endocrine hormone dysregulation, inflammation and inflammatory factors [tumor necrosis factor-alpha (TNF-α), interleukins (ILs)], specific metabolic factors (fat mobilization factors) and protein hydrolysis-inducing factors, etc [2].

For example, some of these cytokines can trigger actions that mimic leptin signaling and inhibit orexigenic growth hormone-releasing peptide and neuropeptide Y (NPY) signaling, inducing persistent anorexia and cachexia.

Symptoms

Because patients with cachexia are in a hypercatabolic state, muscle wasting and weight loss are the most prominent symptoms. As the course of cachexia progresses and with the use of appropriate antitumor therapies, the following types of symptoms may occur:

Major Symptoms

Muscle wasting and weight loss.

Anorexia, nausea, difficulty eating, altered sense of taste and smell.

Constipation, diarrhea.

Chronic pain, abdominal pain.

Weakness and fatigue.

Shortness of breath.

Mental weakness, mental anguish.

Seek medical attention

Cachexia is a concomitant disease and is usually consulted on the basis of the primary disease.

Department of Medicine

Medical Oncology

Tumor-related diseases are the most common cause of cachexia. The patient is usually seen for unexplained weight loss over a short period of time (e.g., sudden weight loss of 5 kg or more without exercise), or for a physical examination that reveals a significant increase in tumor markers.

Emergency Department

Most patients with malignant disease are in the advanced stage of the primary disease. They may suddenly deteriorate and develop critical manifestations such as hemoptysis, gastrointestinal perforation, malignant pleural effusion, malignant pericardial effusion, hematuria, etc., which require immediate consultation at the Emergency Department.

Preparation

Consultation: registration, preparation of information, common problems

Tips for Medical Care

It is recommended to record your recent weight measurement and provide it to your doctor for reference.

Preparation Checklist

Symptom list

Pay special attention to the time of onset of symptoms, special manifestations, etc.

Is there any significant weight loss (e.g., unexplained loss of nearly or more than 5 kg)?

Are there any signs of significant weight loss (muscle and bone contouring visible to the naked eye)?

Are there any symptoms such as nausea, difficulty in eating, anorexia, or change in taste?

Are there any symptoms such as constipation or diarrhea?

Medical History Checklist

Is there a history of malignant tumor?

Is there a history of chronic obstructive pulmonary disease?

Is there a history of chronic heart failure or chronic renal failure?

Is there any other medical history such as liver insufficiency, AIDS, rheumatoid arthritis, etc.?

Checklist

Test results from the last 1 year or earlier to bring with you to your doctor’s appointment

Laboratory tests: blood tumor marker assay, pulmonary function tests, heart failure markers, electrocardiogram, liver function tests, renal function tests, etc.

Imaging tests: X-ray, CT, MRI (magnetic resonance imaging), etc.

Pathological examination: tissue biopsy.

Diagnosis

Diagnosis is based on

Medical history

The patient may have a history of neoplastic disease as well as other chronic wasting diseases.

Clinical manifestations

Patients may have muscle atrophy, weight loss, anorexia, nausea, difficulty eating, and altered sense of taste and smell. There may also be weakness, malaise, and mental anguish.

Diagnostic Criteria

The currently used diagnostic criteria for tumor malignancy are listed below. Any of the following in combination with loss of appetite or systemic inflammation is diagnostic [3-4].

Body mass loss of >5% within 6 months without dieting.

Body mass index (BMI) <18.5 kg/m2 (Chinese) and any degree of body mass loss >2% within 6 months.

Skeletal muscle index of the extremities meeting criteria for sarcopenia (<7.26 kg/m 2 for men and <5.45 kg/m 2 for women) and any degree of body mass loss >2% (using the European Association for the Study of Palliative Care criteria).

Staging

The currently more recognized staging criteria are as follows:

Pre-malignant

Presenting with anorexia and metabolic changes and weight loss of less than 5% of the original body weight within 6 months.

Malignant Stage

Same as the above diagnostic criteria for malignant tumor.

Refractory stage of malignant disease

The tumor continues to progress and is unresponsive to treatment; catabolism is active and the loss of body mass continues uncorrected.

Differential diagnosis

The differential diagnosis of this disease is mainly for the identification of the cause of the disease, which can be diagnosed according to the above criteria.

Treatment

Aim of treatment: try to prolong the patient’s life, and adopt palliative treatment to alleviate the pain of terminal patients.

Treatment principle: Under the premise of standardized anti-tumor treatment, nutritional and pharmacological interventions should be carried out to correct the malignant state of the patient as far as possible, taking into account the actual situation of the patient.

Nutritional intervention

From the perspective of clinical outcomes, nutritional intervention can improve the quality of survival of patients with malignant disease, and even prolong the survival of patients.

The ultimate goal of nutritional intervention for malignant disease is to reverse the loss of body mass and muscle loss, while for patients with refractory malignant disease, the main goal is to reduce malignant disease-related symptoms and improve the overall quality of life.

Nutritional counseling and dietary guidance

It is recommended that patients and their families consult with a medical professional and follow the doctor’s instructions.

Close follow-up (including monitoring of nutritional status, nutritional counseling and dietary guidance) by a professional dietitian (in conjunction with the clinician) may improve the quality of life and even prolong the survival of the patient.

Nutritional counseling and dietary guidance to increase energy and protein intake have been shown to be effective in improving the nutritional status of oncology patients.

Enteral nutrition

Enteral nutrition is a nutritional support method to provide metabolically required nutrients and other nutrients through gastrointestinal tract, including oral and tube feeding, the latter mainly includes nasogastric tube, nasoenteric tube, percutaneous endoscopic gastrostomy tube and percutaneous endoscopic gastrojejunostomy tube, etc. Enteral nutrition is effective for some patients.

Enteral nutrition is effective in some patients. In patients with refractory malignant disease, enteral nutrition can be given without increasing the discomfort associated with eating.

Parenteral nutrition

For patients with malnourished tumors, total parenteral nutrition or supplemental parenteral nutrition is recommended if enteral nutrition cannot be implemented in conjunction with antitumor therapy.

For patients with progressive malignant tumors, nutritional therapy should give priority to enteral nutrition, supplemented by parenteral nutrition, combined with internal and external nutrition, and transformed from internal and external.

In most cases, the use of parenteral nutrition alone is not recommended, especially for refractory malignant disease, because parenteral nutrition may bring certain adverse effects.

Application of nutrients

Omega-3 fatty acids

Omega-3 polyunsaturated fatty acids, including eicosapentaenoic acid and docosahexaenoic acid, have anti-inflammatory effects. Nutritional interventions have been shown to have a positive effect on body mass, with omega-3 fatty acid supplementation increasing the body mass of patients with malignant tumors receiving radiotherapy by approximately 2 kg [5].

Branched-chain amino acids

There is insufficient clinical evidence that supplementation with branched-chain amino acids (BCAAs) improves the nutritional status of patients with malignant tumors.BCAAs inhibit proteolysis while promoting protein synthesis, and have been shown to improve appetite loss [6].

Vitamins, minerals and other dietary supplements

Vitamins and minerals should be supplied in amounts roughly equal to the recommended intakes in the Dietary Reference Intakes, and the use of high doses of micronutrients is discouraged in the absence of special needs.

Pharmacologic interventions

No drugs have been approved for the treatment of malignant tumors at home or abroad. Please consult your physician and strictly follow the doctor’s instructions for the suitability of pharmacological interventions.

Progestogens can increase appetite and food intake, increase body mass, and improve nutritional indicators.

One study found that patients with advanced gastrointestinal tumors or lung cancer who received olanzapine and megestrol acetate had increased body mass and improved appetite and quality of life compared with megestrol acetate alone [7].

Amorelin, a selective GHS-R1a agonist, has become a research hotspot for targeted therapy of tumor malignancy and is the most rigorously evaluated drug for malignancy treatment to date. Some findings have shown that amorelin can increase body mass and alleviate symptoms such as anorexia in patients with advanced non-small cell lung cancer malignancy [8].

Glucocorticoids also improve appetite, and patients with advanced disease can be targeted for potential glucocorticoid intervention because their positive pharmacological effects on end-stage tumors may outweigh the risk of adverse effects.

Other medications, including androgens or selective androgen receptor modulators, nonsteroidal anti-inflammatory drugs, and L-carnitine may improve cachexia in patients with tumors, but evidence from high-quality clinical studies is lacking.

Other interventions

Physical exercise

Exercise improves strength, muscle function, and quality of survival by modulating cytokine expression and possibly synergizing with hormone synthesis. Exercise increases insulin sensitivity, improves the efficiency of protein synthesis, decreases inflammatory responses, and improves immune responses.

The paradigm of exercise combined with nutritional interventions or other interventions may become an effective treatment for cachexia and is expected to be an important component of multidisciplinary treatment.

Psychosocial intervention

Negative psychosocial effects are often present in patients with tumor malignancy.

Psychosocial support as part of multidisciplinary treatment has the potential to alleviate patient distress and family conflict, provide psychological support, reduce social isolation and encourage adherence to treatment.

Prognosis

Cure

Most prognoses are poor. Malignant disease is a manifestation of chronic wasting disease in its final stages, and there is still no effective measure to reverse this process, making it virtually incurable.

Harm

Severe cachexia often reduces the patient’s quality of life, affects the effectiveness of tumor treatment, and shortens the patient’s survival time.

Daily

Daily Management

Dietary management

Increase protein intake.

Take oral supplements as appropriate.

Eat smaller and more frequent meals.

For nutritional interventions, please strictly follow medical advice.

Lifestyle management

Avoid heavy physical exercise, please consult a medical professional for the specific intensity of exercise and do not make decisions on your own.

Maintain a positive attitude and take appropriate physical exercise.

Psychological support

Family members and family caregivers should give full understanding and care to the patient.

In case of emotional instability and depression, promptly confide in family members and provide psychological intervention if necessary.

Disease monitoring

Malignant disease patients and their families should pay attention to observe whether there is any aggravation or recurrence of the disease after treatment, and consult the doctor for review in time if any abnormality occurs.

During the treatment period, family members should pay attention to observe whether there is any damage to the patient’s skin, and help bedridden patients turn over in time to avoid the formation of pressure sores or bedsores.

Prevention

Cachexia is mostly a secondary disease, so the idea of prevention is to treat the primary disease in time, such as malignant tumors.

At the same time, pre-malignant states should be recognized in advance, and interventions such as improving anorexia and malnutrition and correcting metabolic disorders should be taken as early as possible to avoid progression to malignant states.