Chronic Pancreatitis Group Research Articles

A Finger Sweat Chloride Test for the Detection of a High-Risk Group of Chronic Pancreatitis

Mutations of the cystic fibrosis transmembrane conductance regulator (CFTR) gene are associated with chronic pancreatitis in Caucasians. We developed a simple method for measuring finger sweat chloride concentration to test whether CFTR dysfunction underlies chronic pancreatitis in Japan where cystic fibrosis (CF) is rare. We studied 25 patients with chronic (21 alcoholic and 4 idiopathic) pancreatitis and 25 healthy volunteers. Sweat chloride concentrations were measured by a finger sweat chloride test. We analyzed DNA for 20 common CFTR mutations in Europeans, 9 CF-causing mutations in Japanese, and 2 polymorphic loci, a poly-T tract and (TG) repeats, at intron 8. Thirteen patients (52%) had sweat chloride levels >60 mmol/L, a level consistent with CF, while only 4 (16%) healthy subjects exceeded this level. The 29 CF mutations and the 5T allele were detected in neither the patients nor controls. The (TG) 12 allele was common in both the patients (58%) and controls (48%). The (TG) 12/12 genotype was common in alcoholic pancreatitis (29%) compared with the (TG) 11/11 (10%). Patients with the (TG) 12/12 genotype had significantly higher sweat chloride concentrations than the controls. CFTR dysfunction as evidenced by a finger sweat chloride test is present in about half of Japanese patients with chronic pancreatitis, suggesting that this test may be useful for detecting the high-risk group. A higher proportion of the (TG) 12 allele may be a genetic background for elevated sweat chloride concentrations in Japanese patients.

Stem cell factor and macrophage-colony stimulating factor in patients with pancreatic cancer.

Stem cell factor (SCF) and macrophage-colony stimulating factor (M-CSF) have assumed an increasing importance in cancer biology. In the present study we investigated the serum levels of these cytokines in pancreatic cancer patients in relation to controls and to patients with benign lesions of the pancreas (chronic pancreatitis group). The classical tumor markers, such as carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA 19-9) were also tested. We compared the serum levels of cytokines with tumor stage. We also defined the receiver-operating characteristics (ROC) curve for cytokines and classical tumor markers. The cytokines were measured in 47 patients with pancreatic cancer, in 27 patients with chronic pancreatitis and in 35 healthy subjects. SCF and M-CSF were determined using enzyme-linked immunosorbent assay (ELISA). CEA and CA 19-9 were measured by microparticle enzyme immunoassay. There were significant differences in the levels of circulating SCF, M-CSF, CEA and CA 19-9 in the pancreatic cancer patients compared to the control group, but only the serum levels of M-CSF, CEA and CA 19-9 were significantly higher in pancreatic cancer patients compared to the pancreatitis group. The levels of cytokines and tumor markers were higher in patients with a more advanced tumor stage. The M-CSF serum levels correlated positively with the tested tumor markers. The M-CSF area under the ROC curve was higher than the SCF area. These results suggest that M-CSF is a better candidate for a pancreatic cancer tumor marker than SCF.

Plasma Leptin Levels in Rats with Pancreatitis

Diagnosis of pancreatitis is based on the determination of serum amylase and lipase levels. However, recent identification of specific leptin receptors in the pancreas suggests that this peptide may also play some roles in the modulation of pancreatic function. The objective of the present study was to investigate the relationship between serum leptin levels and pancreatitis. Thirty male Wistar rats were divided into 3 groups: the control group, acute pancreatitis group and chronic pancreatitis group. Pancreatitis was induced by injection of ethyl alcohol into the common biliary duct. A sham laparotomy was performed in the control group. Control and acute pancreatitis groups were sacrificed 24 hours later, and chronic pancreatitis group was sacrificed on postoperative day 7. Blood was taken by cardiac puncture for the determination of plasma leptin levels, and the pancreatic tissue was excised for histopathologic confirmation of pancreatitis. Plasma leptin rose significantly from the median of 0.78 +/- 0.12 ng/ml in the control group to 1.92 +/- 0.10 ng/ml and 1.86 +/- 0.13 ng/ml in acute and chronic pancreatitis groups, respectively (p < 0.001, for both). There was no significant difference in the plasma leptin levels between the acute pancreatitis group and the chronic pancreatitis group (p > 0.05). These findings confirm that leptin has a role in pancreas inflammation, and the inflamed tissue can be the source of local production of leptin.

Can IL-2R alpha be a valuable marker along with CA 19-9 in the diagnosis of chronic pancreatitis and pancreatic cancer?

Pancreatic cancer is characterized initially by non-specific abdominal symptoms followed by rapid tumor progression. Although chronic pancreatitis is a benign disorder, it can be one of the causative factors of pancreatic cancer. The level of the tumor marker carbohydrate antigen 19-9 (CA 19-9) in pancreatic cancer does not correlate with the stage of the neoplasm. Soluble interleukin 2 receptor (sIL-2R) is a cytokine that shows increased levels during some inflammatory processes and malignant disorders. Our aim in this study was to investigate whether sIL-2Ralpha levels can be used in association with CA 19-9 in the early diagnosis of pancreatic cancer and chronic pancreatitis. Serum samples were obtained from the blood of 21 pancreatic cancer patients without distant metastasis who were deemed inoperable, 16 chronic pancreatitis patients and 20 normal volunteers. We did not find any significant differences in CA 19-9 levels between normal controls and patients with chronic pancreatitis. There was a significant difference in the levels between the control group and the pancreatic cancer group (p = 0.003) and between patients with chronic pancreatitis and those with pancreatic cancer (p = 0.004). Although there was no significant difference in sIL-2Ralpha levels between the control group and the patient groups, we found a slight correlation between sIL-2Ralpha and CA 19-9 levels in the pancreatic cancer group (p = 0.003, r = 0.623) and a more marked correlation in the chronic pancreatitis group (p < 0.01, r = 0.751). According to our results, sIL-2Ralpha alone is not a good candidate marker in the diagnosis of pancreatic cancer; it can, however, be used in association with CA 19-9 for this purpose.

P16 Inactivation in Pancreatic Intraepithelial Neoplasias (PanINs) Arising in Patients With Chronic Pancreatitis

Patients with long-standing chronic pancreatitis are thought to be at increased risk of developing pancreatic ductal adenocarcinoma, but the mechanism for this increased risk is unknown. Since increasing evidence supports the notion that infiltrating pancreatic ductal adenocarcinomas arise from pancreatic intraepithelial lesions (PanINs), we sought to determine if patients with chronic pancreatitis harbor PanINs with alterations in tumor suppressor genes that are associated with infiltrating pancreatic ductal adenocarcinoma. We identified 122 patients with a diagnosis of chronic pancreatitis and 29 patients with a well-differentiated pancreatic endocrine tumor that underwent pancreatic surgery at the Johns Hopkins Hospital from 1985 to 1999. PanINs from each resection specimen were identified, graded, counted, and correlated with smoking and alcohol history. The expression patterns of p16 and Smad4 were determined in a subset of PanINs by immunohistochemistry, and the pattern of labeling compared with that seen in PanINs associated with infiltrating adenocarcinoma of the pancreas as identified in prior studies, and to PanINs associated with pancreatic endocrine tumor. Duct lesions were present in 80 of the 122 pancreata with chronic pancreatitis (66%). Of 405 duct lesions identified in the chronic pancreatitis group, 7.6% were reactive changes, 65.5% were PanIN-1A, 18% were PanIN-1B, 7.4% were PanIN-2, and 1.5% were PanIN-3. Within the pancreatic endocrine tumor group, 22 PanINs were identified: 15 PanIN-1A, 4 PanIN-1B, and 3 PanIN-2. There were significantly fewer high-grade PanINs in the pancreata with chronic pancreatitis than in pancreata with pancreatic adenocarcinoma (P < 0.0001). Within the chronic pancreatitis group, the 80 patients with PanINs were significantly older than the 42 patients without PanINs (mean age 57.0 +/- 14.1 years vs. 50.9 +/- 14.7 years, P = 0.01). Smoking history was not associated with PanIN prevalence or grade, but patients who reported a history of excessive alcohol consumption had fewer PanINs (25 of 44 harbored PanINs, 57%) than those who did not (54 of 74, 73%, P = 0.07). In the chronic pancreatitis group, 0% of PanIN-1A, 11% of the PanIN-1B, 16% of the PanIN-2, and 40% of the PanIN-3 lesions showed loss of p16 expression, whereas all of the PanINs from patients with an pancreatic endocrine tumor retained p16 expression. All of the PanINs analyzed from patients with chronic pancreatitis retained normal Smad4 expression. We conclude that a significant minority of PanINs arising in patients with chronic pancreatitis show loss of p16 expression. This alteration, common to pancreatic cancer-associated PanINs, may contribute to the predisposition of patients with chronic pancreatitis to develop pancreatic ductal adenocarcinoma.

Study of polymorphisms in the CYP2E1 gene in patients with alcoholic pancreatitis

Cytochrome P450IIEI (CYP2E1) is an ethanol-inducible enzyme. Recently, several novel polymorphisms in the CYP2E1 gene have been identified. A polymorphism at position −35 {G(−35)T} appears to be of functional significance in transcription assays. The aim of this study was to investigate if this and other polymorphisms, at position −1019 {C(−1019)T}, 4808 {G(4808)A}, and 7668 {T(7668)A} of the CYP2E1 gene are associated with alcoholic pancreatitis. DNA was extracted from peripheral blood of 38 patients with alcoholic chronic pancreatitis (CP), 19 patients with alcoholic acute pancreatitis (AP), 46 alcoholic controls (AC), and 155 normal controls (NC). The polymorphisms were examined by digestion with the corresponding restriction endonucleases following PCR amplification. The results have shown that the frequencies of the rare alleles of these polymorphisms were not significantly different between the CP, AP, and AC groups and NC. Therefore, our study results suggest to us that the polymorphisms investigated in the CYP2E1 gene are unlikely to be involved in the susceptibility and pathogenesis of alcoholic pancreatitis.

Elevated serum levels of antibodies to carbonic anhydrase I and II in patients with chronic pancreatitis.

An immune-mediated reaction to pancreatic structures has been postulated for the pathogenesis of chronic pancreatitis (CP). Several reports demonstrate the presence of antibodies to the pancreatic ductal epithelium in some patients suffering from CP. Serum antibodies to carbonic anhydrase I (anti-CA I) and II (anti-CA II) are present in patients affected by idiopathic CP. The aim of this study was to evaluate the presence of anti-CA I and anti-CA II in a series of patients with CP. We studied 78 consecutive CP patients (62 male, 16 female; mean age 48.6 +/- 10.2 years) referred to the Verona University Center for the Study of the Pancreas. As a control group, we studied 26 healthy subjects recruited from among the medical and nursing staff of the center. Serum anti-CA I and anti-CA II levels were quantified by enzyme-linked immunosorbent assay using a standard method with minor modifications. The mean absorbance of antibodies was higher in CP patients than in control subjects (anti-CA I: 0.064 +/- 0.042 vs. 0.047 +/- 0.015, p = 0.051; and anti-CA II: 0.038 +/- 0.02 vs. 0.029 +/- 0.014, p = 0.033). Positive results were arbitrarily defined as absorbance values >0.067 for anti-CA I and 0.047 for anti-CA II. We found anti-CA I and anti-CA II positivity in 21 of 78 (27%) and 20 of 78 (26%) of CP patients, respectively, and in only two of 26 control subjects (7.7%) (p = 0.032 and 0.039). Twenty-two of 26 subjects in the control group (84.6%) and 48 of 78 patients (61.5%) in the CP group tested negative for both antibodies (p = 0.03). None of the control subjects and 12 of 78 (16.6%) of the CP patients tested positive for both anti-CA I and anti-CA II. We observed a significant correlation between anti-CA I and anti-CA II serum levels in control subjects (R = 0.423; p = 0.016) and in CP patients (R = 0.584; p < 0.0001). No correlation was found between serum antibody levels and any of the following variables: length of disease, alcohol consumption, smoking habits, pancreatic surgery, pancreatic calcifications, diabetes, and steatorrhea. Serum levels of anti-CA I and anti-CA II are elevated in some patients suffering from CP.

Early Detection of Pancreatic Cancer following the Diagnosis of Chronic Pancreatitis

Aim: To assess whether patients with misdiagnoses of chronic pancreatitis (CP), followed at an early stage by a diagnosis of pancreatic cancer (PCr), present different epidemiological characteristics from patients suffering either from CP alone or from CP with late degeneration to PCr. Methods: We arbitrarily subdivided our patient series into three groups: (1) 12 CP who developed PCr within 4 years after onset of symptoms; (2) 12 CP developing PCr after the 4th year, and (3) 701 CP with no subsequent development of PCr. The variables studied were age, sex, drinking and smoking habits, tumor localization, and presence of intraductal calcifications and diabetes mellitus at the time of diagnosis of CP. Results: There were no significant differences between CP and ‘late’ PCr in any of the study variables considered. As compared with the CP group, the ‘early’ PCr cases were older (58.7 vs. 40.7 years; p < 0.0001), with a lower proportion of males (58 vs. 88%; p < 0.01), smaller proportions of both smokers (42 vs. 88%; p < 0.0001) and subjects drinking more than 40 g of alcohol/day (42 vs. 86%; p < 0.0001), and a greater incidence of non-insulin-dependent diabetics at the time of diagnosis of CP (25 vs. 3.7%; p < 0.012). As compared with the ‘late’ PCr group, the malignancies in the ‘early’ PCr cases were more often located in the head of the pancreas (100 vs. 50%; p < 0.01). Multivariate logistic regression analysis selected age over 50 (odds ratio OR 13.5, 95% confidence interval CI 2.79–65.5; p < 0.001), smoking habits (OR 0.14, 95% CI 0.04–0.49; p < 0.002), and non-insulin-dependent diabetes (OR 5.91, 95% CI 1.20–29.1; p < 0.028) as variables identifying subjects with ‘early’ PCr. Conclusions: A high suspicion of a pancreatic tumor is necessary when CP is diagnosed in a patient with atypical epidemiological characteristics for this condition, possibly female, aged over 50, who is not a smoker or drinker, and suffers from non-insulin-dependent diabetes.

Genotypes of alcohol-metabolizing enzymes in relation to alcoholic chronic pancreatitis in Japan.

Long-term consumption of large amounts of alcohol is the main cause of chronic pancreatitis. All heavy drinkers, however, do not contract chronic pancreatitis. Although genetic predisposition to alcoholism and alcoholic liver disease has been reported, genetic susceptibility to alcoholic pancreatitis is still a matter of debate. To determine the relation between genotypes of alcohol-metabolizing enzymes and chronic alcoholic pancreatitis, we examined genotype patterns of aldehyde dehydrogenase 2 (ALDH 2), alcohol dehydrogenase 2 (ADH 2) and cytochrome P-4502E1 (CYP2E1) in 54 patients with chronic alcoholic pancreatitis who were diagnosed in general hospitals in all over Japan and compared with those in 30 patients with chronic nonalcoholic pancreatitis or in 46 alcoholics with normal pancreatic function. There were no significant differences in the distribution of genotypes of ALDH 2 and CYP2E1 among those three groups. As for the ADH 2 genotype, distribution of 2(1)/2(1), 2(1)/2(2), and 2(2)/2(2) was 35%, 30%, and 35% in alcoholics with normal pancreatic function; 4%, 39%, and 57% in the chronic alcoholic pancreatitis group; and 0%, 50%, and 50% in the chronic nonalcoholic pancreatitis group, respectively. The frequency of ADH 2(2) allele was significantly higher in the chronic alcoholic pancreatitis group, compared with alcoholics with normal pancreatic function; but, it was not significantly different from that in the chronic nonalcoholic pancreatitis group. We also examined the relation between pancreatic fibrosis or pancreatitis histologically diagnosed and genotypes of alcohol-metabolizing enzymes in alcoholic autopsy cases. Twenty of 31 cases showed moderate or severe pancreatic fibrosis and showed intralobular + interlobular fibrosis, which is characteristic in alcoholic pancreatitis or intralobular fibrosis. ADH 2(2) allele tended to show a high frequency in the intralobular + interlobular fibrosis group, compared with that in the intralobular fibrosis group (75.0% vs. 41.7%, p < 0.1). The chronic pancreatitis group had a significantly higher frequency of the ADH 2(2) allele than that in cases without such findings (87.5% vs. 58.7%, p < 0.05). However, the ALDH 2 and CYP2E1 genotypes showed no significant relation to the findings of pancreatic fibrosis or histological pancreatitis. These data suggest that the risk of chronic alcoholic pancreatitis diagnosed clinically and pathologically seems to be associated with the ADH 2(2) allele in the genotypes of alcohol-metabolizing enzymes.

MYOFIBROBLASTS EXPRESSING α-SMOOTH MUSCLE ACTIN IN GRAFT PANCREATITIS.

372 Myofibroblasts expressing α-smooth muscle actin (SMA) are important contributors to hepatic fibrogenesis, and we have demonstrated that the number of these cells is also increased in chronic pancreatitis. However, their role in graft pancreatitis has not been defined. Aim: The aim of this study was to identify the expression and localization of SMA in graft pancreatitis following initial successful pancreatic transplantation for type I diabetes, compared to its expression in the normal human pancreas and in chronic pancreatitis of the native gland. Methods: Tissue specimens from patients undergoing pancreatic graft resection for vascular mycotic aneurysm or obstructive pancreatitis were compared to specimens obtained from patients undergoing surgery for severe chronic pancreatitis and from patients with a normal pancreas undergoing surgery for abdominal trauma or pancreatic graft transplantation. Tissue from 3 pancreas allografts with obstructive pancreatitis were compared to those from 6 normal controls and 7 patients with severe chronic pancreatitis. All tissue specimens underwent hematoxylin and eosin staining, trichrome staining and immunohistochemical staining for SMA. The stained sections were blindly evaluated using a scoring system from 0-4 for acute and chronic inflammatory changes, severity of fibrosis and, specifically, for acinar cell necrosis, vacuolization and atrophy. All specimens were also graded for the intensity of immunohistochemical staining for SMA in ductal, septal and lobular locations.TableThe pancreata with graft pancreatitis and chronic pancreatitis had increased inflammation, fibrosis and acinar cell atrophy compared to normals. SMA was normally expressed in the smooth muscle cells of the ducts and blood vessels. In the graft pancreatitis group, septal and lobular SMA expression was dramatically increased as seen in the chronic pancreatitis group. Conclusions: These findings indicate that SMA expression is markedly increased in the septal and lobular areas in graft pancreatitis and is associated with fibrosis, as seen in chronic pancreatitis. The appearance of SMA-positive myofibroblasts in graft pancreatitis may contribute to pancreatic fibrogenesis and loss of graft function.

Quantification of human lithostathine S2-5 forms using the antibody to the N-terminal peptide region.

Lithostathine S2-5 inhibits in vitro crystal growth of CaCO3. We developed an antibody against the peptide region responsible for inhibitory effect to determine whether lithostathine S2-5 levels are different in the pancreatic juice of patients with and without chronic pancreatitis. The antibody against the synthetic peptide of the N-terminal end of lithostathine S2-5 detected lithostathine S2-5 but not lithostathine S1 or lithostathine extracted from pancreatic calculi. Lithostathine S2-5 was detected in samples of pancreatic juice protein by immunoblotting using the specific antibody. The concentration of lithostathine S2-5 was compared between control and chronic pancreatitis groups. The mean concentrations of lithostathine S2-5 were significantly (p=0.002) lower in chronic pancreatitis, 16.3 microg/mg of total protein, than in the control, 47.1 microg/mg of total protein. A decreased concentration of lithostathine S2-5 seems to increase the risk of stone formation in the ducts during the course of chronic pancreatitis because of insufficient inhibition of CaCO3 crystal growth.

Secretory immunoglobulin A in pancreatic juice and pancreatic tissue of patients with chronic pancreatitis

Background—The predominace of secretory IgA (S-IgA) in intestinal secretions compared with blood is well established, but concentrations of this protein in pancreatic juice and its origin, especially in chronic pancreatitis,...

Resting energy expenditure in patients with alcoholic chronic pancreatitis

The aim of this study was to assess resting energy expenditure in patients with chronic pancreatitis; 33 patients with alcohol-related chronic pancreatitis (group 1: 13 normal weight, group 2: 20 underweight) and 11 undernourished patients without identifiable disease (group 3) were studied. Body composition was determined by bioelectric impedance analysis and fat-free mass was similar among the three groups (76.4 +/- 1.5%, 78.6 +/- 1.3% and 76.8 +/- 2.1% for groups 1, 2, and 3, respectively). The measured resting energy expenditure (REE) was higher than the predicted EE (Harris and Benedict formula and Cunningham's equation) for the underweight patients with chronic pancreatitis (group 2) (P < 0.05), but not for the two other groups. According to Cunningham's equation, 65% of the group 2 patients were hypermetabolic (REE > 110% of predicted EE) versus 23.1% and 20% in groups 1 and 3. When adjusted for fat free mass, REE was significantly (P < 0.01) higher in group 2 (35.0 +/- 0.9 kcal/kg/24 hr) than in the other two groups (30.1 +/- 0.7 kcal/kg/24 hr and 30.8 +/-1.4 kcal/kg/24 hr in groups 1 and 3, respectively). During chronic pancreatitis, weight loss is accompanied by hypermetabolism, which should be taken into consideration during nutritional support.

New chronic pancreatitis model with diabetes induced by cerulein plus stress in rats.

To establish a new experimental model of chronic pancreatitis (CP) with diabetes, we investigated pancreatic endocrine function, blood flow, and histopathology in CP induced by repetition of cerulein injection plus water immersion stress in rats. CP rats were treated with water immersion stress for 5 hr and two intraperitoneal injections of 20 micrograms/kg body weight of cerulein once a week for 16 weeks. In the CP group, pancreatic contents of protein, amylase, elastase, and lipase significantly decreased to 64, 38, 23, and 68% of the control group, respectively. In oral glucose tolerance test (glucose 2 g/kg body wt), blood glucose level in the CP group was 212.1 +/- 97.8 mg/dl (mean +/- SD) at 30 min and was significantly higher than the control group (126.3 +/- 15.4 mg/dl)(P < 0.05). Two of seven rats in the CP group showed an obvious diabetic insulin in the CP group was 640.1 +/- 148.7 pM, significantly lower than in the control group (1133.4 +/- 242.0 pM)(P < 0.001). However, insulin content in the pancreas was 12.37 nmol/pancreas). In CP rats, winding and dilatation of surface blood vessels and gland atrophy were evident. Marked fibrosis, fatty changes, and destruction of lobular architecture were also demonstrated microscopically, although the structure of each pancreatic islet was preserved and each islet was fully stained with anti-insulin antibody. In the CP group, pancreatic blood flow by the hydrogen gas-clearance method was 197.6 +/- 33.0 ml/min/100 g, which was significantly less than the control group (276.2 +/- 19.1 ml/min/100 g) (P < 0.001). Thus, we conclude that the CP model induced by cerulein plus stress is a new CP model with diabetes in rats, in which the glucose tolerance was impaired without loss of insulin reserve.

Endoscopic Ultrasonography in Chronic Pancreatitis

The usefulness and accuracy rate of endoscopic ultrasonography (EUS) in the diagnosis of chronic pancreatitis (CP) were prospectively evaluated in 81 patients with suspected pancreatic disease. All underwent EUS, abdominal ultrasonography (AUS), and computed tomography (CT), and endoscopic retrograde cholangiopancreatography (ERCP) was performed in 55 of the cases. The diagnosis of CP was established in 44 patients (CP group) including 24 with a calcified form. No pancreatic disease was observed in 18 patients (control group), and 19 patients had a pancreatic tumor. In the CP group AUS was less accurate than EUS in visualizing the pancreas, performances of CT scan being identical to EUS in this respect. A good correlation was observed between EUS and ERCP for visualization and measurement of the Wirsung duct. The most significant changes observed by EUS in the CP group were dilatation of the main pancreatic duct, heterogeneous echogenicity of the pancreatic parenchyma, and cysts < 20 mm in size even in noncalcified CP or with normal pancreatograms. Sensitivity of EUS for diagnosis of CP was 88% (AUS, 58%; ERCP, 74%; CT scan, 75%), the specificity being 100% for ERCP and EUS, 95% for CT scan, and 75% for AUS. The good performances of EUS allow early diagnosis of CP in symptomatic patients since heterogeneous echogenicity of the pancreatic parenchyma seems to be almost specifically associated with the disease.

Changes in plasma fatty acid profile in Japanese patients with chronic pancreatitis.

The serum zinc, prealbumin, retinol-binding protein and carotene concentrations and the plasma fatty acid composition were determined to assess the nutritional condition of 24 patients with chronic pancreatitis compared with that of 20 healthy controls. The daily food intake and faecal fat excretion of the two groups were also measured. In the chronic pancreatitis group, the calorie and fat intakes were significantly lower than those of the controls. Serum levels of zinc, prealbumin and carotene were also significantly lower than those of the controls. Percentages of plasma linoleic and arachidonic acids were low, while percentages of palmitoleic acid, eicosapentaenoic acid and docosahexaenoic acid were high. Fish oil intake correlated negatively with plasma linoleic acid concentration (P < 0.05). The above results indicate that the relatively high intake of fish oil and the relatively low intake of dietary fat in Japanese patients with chronic pancreatitis with a mild degree of steatorrhoea results in an abnormally low plasma level of linoleic acid.

Faecal triglycerides and fatty acids in the differential diagnosis of pancreatic insufficiency and intestinal malabsorption in patients with low fat intakes.

To investigate possible parameters for the differential diagnosis of steatorrhoea in patients with low fat intakes, faecal specimens were analysed from 15 patients with steatorrhoea due to chronic pancreatitis and seven patients with steatorrhoea due to intestinal malabsorption. The fat intakes of the patients ranged from 30.1 to 60 g, less than the average in American and European patients. The group with pancreatic steatorrhoea showed a significantly lower faecal output than the group with intestinal steatorrhoea but the two groups did not differ significantly in their total faecal fat excretion or concentration. The percentage triglycerides and the molecular ratio of triglycerides to fatty acids in the faeces were significantly higher (P < 0.01) in the group with pancreatic steatorrhoea than in those with intestinal steatorrhoea. The molecular percentage ratio of triglycerides to fatty acids was 6.8 +/- 2.2 for the chronic pancreatitis group and 2.4 +/- 1.0 for the intestinal malabsorption group; while the respective faecal hydroxy fatty acid contents were 3.1 +/- 3.6% and 10.1 +/- 3.3% (means +/- SDs). These latter two parameters appeared to be the most valuable for distinguishing the two forms of steatorrhoea.

Collagenolytic activity in human pancreatic tissue with different degrees of fibrosis.

The present study was designed to establish a valid method for expressing collagenolytic activity in pancreatic tissue with different degrees of fibrosis. Collagenolytic activity was measured in pancreatic tissue of control and alcoholic chronic pancreatitis (CP) patients and data were expressed as percent digestion/mg tissue or as percent digestion/mg protein obtaining different results. The values were 18.4 +/- 4.7% digestion/mg tissue in the control group, and 8.4 +/- 3.2% digestion/mg tissue in the chronic pancreatitis group (p < 0.001). When collagenolytic activity was expressed as percent digestion/mg protein, measured by the Bradford assay, the values of the control group were 190.2 +/- 69.0% digestion/mg protein, and those of chronic pancreatitis patients were 187.2 +/- 61.7% digestion/mg protein (p = ns). Protein determination in pancreatic tissue of control and CP patients was seen to be influenced by the method assayed. Protein content per mg of fresh tissue, measured by the methods of Lowry, Bradford, and Bradford-SDS, were similar and twofold higher in controls than in CP samples. However, the Kjeldahl assay showed that protein content per mg of dry tissue was the same in both groups. The high degree of fibrosis in the pancreas of CP patients (60.2 +/- 28.0%) with regard to controls (4.7 +/- 1.8%) (p < 0.001) and the low response of collagen proteins to the Lowry and Bradford assays could explain the differences observed in protein content of human samples.(ABSTRACT TRUNCATED AT 250 WORDS)

Progression of alcoholic acute to chronic pancreatitis.

Alcoholic chronic pancreatitis usually progresses from acute attacks to chronic pancreatitis within one to 19 years. The factors responsible for the appreciable variability in progression are unclear. In this study the relation between progression and the incidence and severity of acute episodes in a large cohort of patients with alcoholic chronic pancreatitis was analysed. All patients with at least one documented episode of acute pancreatitis have been studied prospectively over the past 30 years according to our protocol. Patients were classified according to their long term course into (a) calcific (n = 185), (b) non-calcific (n = 30), and (c) non-progressive (n = 39) chronic pancreatitis groups. The yearly incidence of acute attacks of pancreatitis was significantly higher in groups (a) and (b) than in group (c). Furthermore, the progression rate to advanced chronic pancreatitis (groups (a) and (b)) correlated with the incidence of severe pancreatitis (associated with pseudocysts in more than 55%). Pseudocysts were located primarily in the cephalic pancreas in groups (a) and (b) (58-71%) and in the pancreatic tail in group (c) (61%). In conclusion, these data suggest that the progression of acute to chronic pancreatitis is closely related to the incidence and severity of acute attacks. This finding and the primary location of pseudocysts in the cephalic pancreas (groups (a) plus (b)) are compatible with the 'necrosis-fibrosis' pathogenetic hypothesis.

Relationship between postprandial release of CCK and PP in health and in chronic pancreatitis

The aim of this study was to investigate the relationship between postprandial release of cholecystokinin (CCK) and pancreatic polypeptide (PP) in healthy subjects and patients with chronic pancreatitis (CP). 14 patients with CP and 14 age-matched healthy subjects were studied. Diagnosis of CP was confirmed by standardized imaging modalities (ERCP and CT). Exocrine pancreatic function was assessed in all 28 subjects using the pancreolauryl serum test (PLT). An oral test meal was administered to stimulate endogenous hormone release. Plasma samples were taken before and at several time points after the test meal. CCK and PP plasma levels were measured by specific radioimmunoassays. Basal CCK and PP plasma levels were not different between patients with CP and controls, and were not correlated in either group. However, a direct linear correlation between integrated postprandial release of CCK and PP was found in healthy subjects ( r = 0.74, P<0.005). This postprandial coupling was not evident in patients with CP ( r = 0.16; n.s.). Peak fluorescein serum concentration in patients with CP and steatorrhea (SCP) ( n = 6) was <2.5 μg/ml, and CCK and PP responses to the meal were significantly impaired ( CCK response = 61 ± 14 pmol/l/120 min in SCP vs. 110 ± 14 in controls, P<0.05; PP response = 3920 ± 1773 pg/ml/120 min in SCP vs. 13418 ± 3299 in controls, P<0.05). In patients with mild/moderate exocrine insufficiency, CCK and PP responses varied greatly and were not different from controls. Response of PP, but not CCK, was significantly correlated with the PLT result in the CP group ( r = 0.70; P<0.01). Our data point to a physiological relationship between postprandial release of CCK and PP. This link is interrupted in patients with chronic pancreatitis.