Biological Markers in Patients With Pancreatic Cancer Experiencing Weight Loss

Role of Caspase-3, Phosphatidylinositol-3 Kinase (PI3K), and 3-methylhistidine (3-MH) in the Pathophysiology of Skeletal Muscle Loss in Weight-losing Pancreas Cancer Patients

RATIONALE: Learning about biological markers in patients with pancreatic cancer and cachexia may help doctors predict patient outcome and may help the study of cancer in the future.

PURPOSE: This laboratory study is examining biological markers in patients with pancreatic cancer experiencing weight loss.

OBJECTIVES:

• Compare levels of caspase-3 and phosphorylated Akt (pAkt) in the rectus abdominous muscle of patients with pancreatic cancer who are experiencing cachexia and are undergoing surgery for diagnosis or primary therapy with patients who have not lost weight and are undergoing abdominal surgery for nonmalignant conditions.
• Compare levels of urinary 3-methylhistidine (3-MH) in these patients.
• Evaluate possible correlations of caspase-3 activity, pAkt, and urinary 3-MH with early time to progression and subsequent lean body weight loss in patients with pancreatic cancer.
• Associate excretion of urinary 3-MH with higher levels of caspase-3 activity and pAkt to analyze the utility of 3-MH as a marker of skeletal muscle proteolysis.

OUTLINE: This is a pilot study.

During surgery, a muscle biopsy is performed and approximately 1 cm of rectus abdominous muscle is obtained for analysis. Caspase-3 activity and total/phosphorylated phosphatidylinositol-3 kinase and Akt are measured in muscle biopsies by western blot analysis. 3-methylhistidine activity is measured in urine samples.

After completion of study, patients with pancreatic cancer are followed postoperatively at 3 and 6 months.

PROJECTED ACCRUAL: A total of 36 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• Meets 1 of the following criteria:

  • Diagnosis or suspicion of pancreatic cancer

    • Any stage disease allowed
    • At least 5% weight loss within the past 6 months
    • Scheduled to undergo exploratory surgery

  • Scheduled to undergo exploratory surgery for suspected nonmalignant condition

    • No weight loss OR weight loss due to specific reason (e.g., bowel obstruction, infection, or nausea/vomiting)

• No cancer diagnosis other than primary pancreatic carcinoma

PATIENT CHARACTERISTICS:

• ECOG performance status 0-3
• Life expectancy ≥ 12 weeks
• No pacemakers or implanted defibrillators

PRIOR CONCURRENT THERAPY:

• Prior or concurrent chemotherapy and radiotherapy allowed

• Prior or concurrent biological therapy and surgery allowed

• At least 4 weeks since prior corticosteroids or anabolic steroids

• Other concurrent anticancer therapy allowed

• No concurrent corticosteroids or anabolic steroids, thalidomide, eicosapentaenoic acid (EPA), or Juven for weight loss

  • Concurrent steroids (i.e., antiemetics) associated with chemotherapy allowed

• No concurrent nutritional supplements with EPA