Unintentional weight loss is a common and serious problem for people with pancreatic cancer. It can lead to a lower tolerance for treatments, a poorer quality of life, and a higher risk of death. This article examines the causes of weight loss in pancreatic cancer patients and provides an overview of supportive care strategies aimed at stabilizing or reversing this weight loss and improving overall outcomes.
The Prevalence and Impact of Weight Loss in Pancreatic Cancer
Weight loss is highly prevalent among patients with pancreatic cancer (PC), with up to 85% experiencing it at the time of diagnosis. Even in the early stages of the disease, nearly half of patients exhibit preoperative weight loss, and a staggering 80% will develop progressive weight loss after diagnosis. This significant prevalence underscores the importance of understanding and addressing this issue.
Weight loss in pancreatic cancer has significant implications for patients' health and survival. It is a predictor of poor outcomes in all stages of the disease. Studies have shown that decreased lean body mass and/or weight are predictors for toxicity, mortality, postoperative infections, length of hospitalization, and therapeutic intensity. Weight loss also correlates with shorter progression-free survival (PFS) and overall survival (OS), decreased response to chemotherapy, lower quality of life (QOL), and declining performance status.
Causes of Weight Loss in Pancreatic Cancer
Weight loss in pancreatic cancer is complex and can be attributed to several factors, including:
Anorexia
Anorexia, or loss of appetite, is a common contributor to weight loss in pancreatic cancer. It is mediated by the inability of the hypothalamus to respond to energy deficit signals. Several factors can contribute to anorexia, including pain, fatigue, depression, dysmotility, constipation, chemosensory disturbances (changes in smell and taste), vomiting, early satiety, and loss of appetite.
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Anorexia also has a negative social impact, leading to changes in social encounters and relationships, as well as feelings of helplessness, anxiety, and distress. Patients may experience distress related to dietary intake and gut symptoms such as gas, belching, bloating, pain/discomfort, and diarrhea, all of which can contribute to weight loss.
Malabsorption
Malabsorption occurs when the body is unable to properly absorb nutrients from food. In pancreatic cancer, malabsorption is often caused by pancreatic exocrine insufficiency (PEI). PEI is a common complication of PC that occurs when the pancreas is unable to maintain normal digestive function, specifically the secretion of proteases, lipase, and amylase. These enzymes are essential for breaking down proteins, fats, and carbohydrates, respectively. When their secretion is impaired, it leads to malabsorption and malnutrition. PEI negatively impacts QOL and is associated with poor survival.
Cachexia
Cachexia is a multifactorial syndrome characterized by progressive involuntary weight loss, loss of skeletal muscle mass (with or without adipose loss), and systemic inflammation. It results from a complex interaction between the tumor, the host, and the therapy. Cachexia can occur even before weight loss becomes apparent, a stage known as "precachexia." Preclinical models suggest that chemotherapy and targeted agents can contribute to cachexia through mitogen-activated protein kinase-dependent muscle atrophy, mitochondrial depletion, and muscle weakness leading to disuse atrophy. Despite its high prevalence and potential for mortality, PC-associated cachexia is often underdiagnosed and undertreated due to the lack of an established treatment approach.
The stages of cachexia occur across a spectrum, starting with precachexia (WL <5%), then cachexia (associated with systemic inflammation), and ending with refractory cachexia (defined by a loss of body reserves and rapidly deteriorating nutritional status). It's important to note that skeletal muscle and adipose tissue may behave independently during weight loss, and muscle wasting can be obscured in obese patients with cancer.
Other Factors
In addition to anorexia, malabsorption, and cachexia, other factors can contribute to weight loss in pancreatic cancer patients. These include:
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- Tumor location: Tumors in the head of the pancreas can block the bile duct, leading to jaundice and malabsorption.
- Treatment side effects: Chemotherapy and radiation therapy can cause nausea, vomiting, and diarrhea, which can decrease appetite and nutrient absorption.
- Diabetes: Some people diagnosed with pancreatic cancer are found to be newly diabetic, which can affect their ability to process sugar and maintain a healthy weight.
- Shortfall of digestive enzymes: Shortfall of digestive enzymes can lead to tissue breakdown in early stages of pancreatic cancer.
Assessment of Weight Loss in Pancreatic Cancer
Given the significant impact of weight loss on pancreatic cancer patients, a comprehensive approach to its assessment and management is crucial. This approach should be tailored to each individual and should include the following:
Screening for Weight Loss
All patients should be screened for weight loss at presentation and prior to diagnosis. A quick review of weight loss history can help determine the extent of PAWL. Assessment of weight loss over time is a standardized diagnostic characteristic used to identify and document adult malnutrition.
Nutrition Screening
Nutrition screening using a validated tool allows for identification and referral of at-risk patients to a registered dietitian for complete nutrition assessment and intervention. Two nutritional screening tools have been vetted for both inpatient and outpatient use: the malnutrition screening tool (MST) and the patient-generated subjective global assessment (PG-SGA).
The MST is a quick, valid, and reliable screening tool consisting of two questions regarding appetite and recent unintentional weight loss. The PG-SGA is a valid and reliable assessment tool to identify and triage malnourished patients with cancer in both the inpatient and outpatient setting. Patients deemed to be at risk for malnutrition should be referred to a registered dietitian for nutrition assessment.
Nutrition Assessment
A full nutrition assessment involves obtaining a food history, evaluation of anthropometric measurements, review of medical history, biochemical data, medical tests and procedures, and completion of a nutrition-focused physical assessment. Routine assessment of food intake should include patient estimate of overall food intake and 24-hour food recall. An oncology-focused assessment also involves reviewing the oncologic treatment plan to determine current and anticipated nutrition issues.
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Assessment for Pancreatic Exocrine Insufficiency (PEI)
Although there are several tests to diagnose pancreatic exocrine insufficiency, their clinical application and use is variable. Definitive identification of PEI in PC patients is challenging; thus, PEI is usually a clinical diagnosis. Direct measures of gastric and duodenal contents such as a secretin-cerulein or secretin-pancreozymin tests are expensive, invasive, and only available at specialized centers. Other tests such as fecal fat test, fecal elastase, and coefficient of fat absorption (CFA) are more clinically available but may be cumbersome.
Fecal elastase measurements are often used to diagnose PEI. Fecal elastase is less sensitive than CFA collection but quite specific. In standard PC care, PEI diagnosis is often established clinically based on patients’ history and reported symptoms (unintentional weight loss, change in stool, bloating after meals, etc.).
Serum Testing
There is no widely adopted serologic evaluation of patients with PAWL. However, weight loss in cancer patients has been associated with markers of inflammation, low levels of serum testosterone in men, and vitamin deficiencies. Measuring serum inflammation in PC patients with a Glasgow Prognostic Score (GPS) has shown prognostic significance in several studies and is predictive of surgical outcomes. The GPS and other markers of inflammation are consistently associated with weight loss and cachexia in cancer patients.
Male hypogonadism (MH) is a common complication in advanced cancer and prominent in cancer patients with cachexia. Hypogonadism in cancer cachexia is associated with decreased strength, poor nutritional status, decreased performance status, depression, and decreased survival.
There has been little published material regarding serum assessment for vitamin and mineral deficiencies in patients with PC. Most available literature is related to the post-pancreatic resection setting or in the broader topic of PEI from all causes (chronic pancreatitis and cystic fibrosis included). After resection, reported nutritional deficiencies include fat-soluble vitamins A, D, and E, vitamins B12 and B6, iron, zinc, selenium, biotin, and copper. Vitamin D deficiency has been reported in patients with PC and may contribute to poor outcomes.
Muscle Volume Measurements
Muscle volumes can be measured and sarcopenia diagnosed using several modalities: computed tomography (CT) or magnetic resonance imaging (MRI); appendicular skeletal muscle index obtained from dual energy x-ray absorptiometry (DEXA); mid-upper-arm muscle area by anthropometry; and whole-body fat-free mass index determined by bioimpedance analysis. Morphometric analysis of diagnostic CT or MRI slices can be used to calculate whole-body skeletal muscle and adipose tissue, to assess muscle quality, and to detect presence of myosteatosis.
Management of Weight Loss in Pancreatic Cancer
Optimal approaches to the diagnosis and management of PC weight loss and cachexia are understudied and poorly understood; however, nutritional intervention can improve QOL and OS in advanced PC. Recognizing and treating malnutrition in advanced cancer early in the treatment process is essential for improving outcomes. Furthermore, nutritional support in PC is complicated and influenced by many factors including tumor response, diabetes, pain management, altered physiology, and other comorbidities.
Nutritional Support
Dietitians play a central role in the successful management of PAWL. Nutrition interventions for PAWL have improved weight, QOL, and outcomes. Dietitians can provide essential dietary suggestions, identify PEI, and provide recommendations for oral nutritional support.
- Dietary Modifications: Adjusting the diet to meet the patient's individual needs is crucial. This may involve increasing calorie and protein intake, providing soft foods that are easier to swallow, and encouraging small, frequent meals.
- Pancreatic Enzyme Replacement Therapy (PERT): For patients with PEI, PERT is essential to improve nutrient absorption. Pancreatic enzymes help break down fats, proteins, and carbohydrates, allowing the body to absorb them more effectively.
- Nutritional Supplements: Nutritional supplements can help patients meet their nutritional needs when they are unable to eat enough food. These supplements can provide essential vitamins, minerals, and calories.
- Orexigenic Agents: Orexigenic agents are medications that stimulate appetite. While commonly used orexigenic agents that stimulate appetite have no definite benefit.
Other Supportive Measures
In addition to nutritional support, other supportive measures can help manage weight loss in pancreatic cancer patients:
- Pain Management: Effective pain management can improve appetite and overall well-being.
- Management of Nausea and Vomiting: Medications can help control nausea and vomiting, making it easier for patients to eat.
- Exercise: Gentle physical activity can help to increase appetite and help patients maintain their strength and fitness.
The Role of Early Detection
Earlier detection for pancreatic cancer will need multiple tests, like heart disease, for example. With heart disease you look at a lot of factors like family history, personal history, cholesterol, blood pressure, smoking, and diabetes to assess risk, not just one thing.