Evidence of chromosome instability in chronic pancreatitis.

In the current study we analyzed chromosome instability on peripheral blood lymphocytes cultured from 7 untreated patients with chronic pancreatitis (CP) by assessing telomeric associations (TAS), chromosome aberrations (CA) and sister chromatid exchanges (SCE). Seven healthy individuals were also analyzed. Mean frequencies of TAS were significantly higher in CP patients (X +/- SE: 11.00 +/- 2.37) compared to controls (1.00 +/- 0.30) (p<0.001). Chromosomes preferentially involved in TAS were: 9, 20, 16 and 21, being the most affected arms: 9p, 20q, 16p, 9q and 21q. All these terminal bands were coincident with cancer breakpoints (p<0.03), two of them (40%) were specifically associated to pancreatic carcinoma rearrangements. Three bands (60%) were coincident with oncogene location. The mean frequency of CA was significantly higher in patients (3.88 +/- 0.80) compared to controls (0.63 +/- 0.49) (p<0.001). Chromosomes 1, 2 and 13 were the most damaged. No specifically affected breakpoints were found. SCE analysis showed higher levels in patients (8.33 +/- 0.70) than in controls (6.62 +/- 0.34) (p<0.025), but no differences were observed in cell cycle kinetics. Our results clearly indicate that CP patients exhibit chromosome instability, showing the presence of an unstable genome that could be related to the cancer development observed in this disease.

Bone mineral density in patients with pancreatic insufficiency and steatorrhea.

OBJECTIVES: Low bone mineral density (BMD) has been demonstrated in some patients with chronic intestinal disorders accompanied by diarrhea and malabsorption. However, very few studies have evaluated BMD in patients with pancreatic insufficiency due to cystic fibrosis. Our aim was to assess the prevalence and severity of bone loss in a cohort of patients with pancreatic insufficiency as a consequence of chronic pancreatitis. METHODS: Fourteen patients with chronic pancreatitis were studied. All of them presented with severe pancreatic insufficiency (secretin test: bicarbonate < or = 40 mEq/L) and steatorrhea (fecal fat > 7 g/day) and had been abstinent from alcohol for a median of 2.5 yr (range 1-15 yr). BMD was measured with a total-body scanner for dual-energy x-ray absorptiometry. Results were expressed as T-score (number of SD by which a patient density differs from the mean of sex-matched 30-yr-old healthy controls) in lumbar spine (L2-L4) and femoral neck. Total serum calcium, 25-(OH)D3, alkaline phosphatase, and midmolecular parathyroid hormone were determined. RESULTS: Ten patients demonstrated osteopenia (T-score -1 to -2.5) in the lumbar spine and in the femoral neck. Three patients displayed osteoporosis (T-score < -2.5) in the lumbar spine and two in the femoral neck. Mean T-scores (+/- SEM) were -1.44 +/- 0.37 in the lumbar spine and -1.79 +/- 0.27 in the femoral neck. Total and ionic serum calcium, serum parathyroid hormone, and alkaline phosphatase were in the normal range in all patients. Serum 25-(OH)D3 was below normal range in 7 of 12 patients. T-scores of patients with pancreatitis of alcoholic etiology (n = 10) were similar to those of nonalcoholic patients (n = 4). BMD did not correlate with age, bicarbonate secretion, fecal fat excretion, stool volume, parameters of mineral metabolism, duration of alcoholism, or mean alcohol intake. CONCLUSIONS: Most patients with pancreatic insufficiency as a consequence of chronic pancreatitis exhibit osteopenia, and some show evidence of osteoporosis. Identifying the intimate mechanisms for low BMD are beyond the limitations of the present study. More in-depth metabolic studies are necessary to define the pathogenic mechanism of osteopenia associated with chronic pancreatic disorders.