Pancreatic Polypeptide is Increased in Patients with Advanced Malignant Disease

Background: Augmented secretion of pancreatic polypeptide (PP) has been demonstrated in patients with severe systemic diseases or endocrine tumors. The aim of this study was to evaluate PP and autonomic neuropathy in patients with advanced malignant disease. Materials and Methods: Basal PP assessments and five cardiovascular tests for autonomic function were used. Twenty patients, including 11 patients with lung cancer (69 yrs±11, mean±SD) and 10 healthy age-matched controls, were studied. Results: PP levels were significantly higher in the patients than in the controls (pmol/L 107.0±111.4 versus 28.2±13.4, p<0.05). In the parasympathetical tests, the patients showed significantly decreased heart rate response to the Valsalva manoeuvre (ratio 1.20±0.19 versus 1.46±0.23, p<0.005). Also, in the sympathetical tests, the blood pressure response to standing up was significantly decreased (mmHg -3.84±17.53 versus 10.80±8.89, p<0.05). The heart rate response to standing up and deep breathing, as well as the blood pressure response to sustained handgrip, did not differ significantly between the groups. In spite of the apparent autonomic dysfunction among cancer patients with advanced malignant disease, PP levels were significantly higher in these patients when compared with healthy controls. Conclusion: PP levels were significantly higher in patients with advanced cancer than controls, regardless of autonomic dysfunction in the cancer patients. This finding supports the hypothesis that PP may, in some cancer patients, be a marker of advanced malignant disease. Previous studies have shown that pancreatic polypeptide (PP) is reduced in diabetic patients with autonomic neuropathy (1,2). PP consequently has been considered a useful marker of vagal efferent integrity (1,2). However, other studies have shown augmented PP secretion regardless of autonomic dysfunction in patients with severe chronic obstructive pulmonary disease as well as in patients with systemic lupus erythematosus (3,4). PP secretion has been localized to a specific population of human islet cells and has also been shown to be produced and released by pancreatic endocrine tumors (5). PP-producing tumors are mostly located in the pancreas and may present as three pathological lesions: pure PP-omas, mixed tumors with minor PP cell population and PP-cell hyperplasia. Numerous types of extrapancreatic endocrine tumors are able to synthesize and secrete PP (5,6). The aim of this study was to assess serum PP concentrations in patients with advanced malignant disease including lung cancer. We also assessed autonomic neuropathy as an indirect measure of vagal stimulation (7-10). Since all these test results may be age-dependent, an age-matched control group was included (6,11). Materials and Methods