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Endoscopic measurement of pancreatic juice secretory flow rates and pancreatic secretory pressures after secretin administration in human controls and in patients with acute relapsing pancreatitis, chronic pancreatitis, and pancreatic cancer.

Secretory flow rates were measured inside the main pancreatic duct during endoscopic retrograde cholangiopancreatography (ERCP) in patients with acute relapsing pancreatitis, chronic pancreatitis, and pancreatic cancer and in controls after intravenous administration of secretin. Peak secretory flow rates in these groups were 5.04 +/- 1.74, 0.71 +/-1.28, 0.60 +/- 1.37, and 4.13 +/- 0.88 ml/min, respectively. Peak secretory pressures were also measured intraductally in patients with acute relapsing pancreatitis and pancreatic cancer and in controls and were 402 +/- 69, 75 +/- 161, and 403 +/- 99 mm pancreatic juice, respectively. Peak secretory flow rates and pressures measured in controls during constant administration of secretin were similar to those measured when secretin was administered as a bolus.

Endoscopy↗

Serum cathodic trypsin-like immunoreactivity, pancreatic lipase, and pancreatic isoamylase as diagnostic tests of chronic pancreatitis or pancreatic steatorrhea.

We compared serum concentrations of cathodic trypsin-like immunoreactivity, pancreatic lipase, and pancreatic isoamylase as diagnostic tests of chronic pancreatitis (and of pancreatic steatorrhea in the 41 patients with steatorrhea) in 105 patients (57 men, 48 women) consecutively investigated because of clinical suspicion of chronic pancreatitis. Chronic pancreatitis (36 patients), pancreatic steatorrhea (24 patients), and other diseases were diagnosed without knowledge of the serum levels of the three enzymes. When evaluated by means of receiver operating characteristic curves, no differences were found in diagnostic performance of the enzymes with regard to chronic pancreatitis or pancreatic steatorrhea. The sensitivity and specificity for recognition of chronic pancreatitis ranged from 0.306 to 0.444 and from 0.942 to 0.986 when the discrimination values were chosen to give highest efficiencies. The similar ranges for pancreatic steatorrhea were 0.500-0.708 and 0.882-0.941. In conclusion, none of the three enzymes had any advantage over the others as diagnostic tests of chronic pancreatitis or of pancreatic steatorrhea. Only positive test results have clinical importance because of the low sensitivities of the three enzymes.

Adult↗

Synthesis and localization of pancreatic secretory proteins in pancreatic acinar-like metaplasia in the distal part of the oesophagus. Pancreatic acinar metaplasia: another source of pancreatic enzymes!

BACKGROUND: Pancreatic acinar-like metaplasia has previously been described in the gastric mucosa and in the distal part of the oesophagus. The resemblance to pancreatic acinar cells prompted us to study the possible occurrence of secretory pancreatic proteins in these cells. METHODS: Seven specimens obtained from the distal oesophagus at gastroscopy where routine microscopy showed pancreatic acinar-like metaplasia were selected for this study. Sections were subjected to immunohistochemical detection of trypsinogen, pancreatic elastase, procarboxypeptidase B and pancreatic secretory trypsin inhibitor using specific antisera. An alkaline-phosphatase-conjugated oligodeoxynucleotide probe, complementary to the transcript for trypsinogen 2 (anionic) was used for in situ hybridization. RESULTS: Cells with pancreatic acinar-like metaplasia were immunoreactive to all pancreatic secretory proteins studied. In situ hybridization showed the presence of trypsinogen 2 mRNA in pancreatic acinar-like metaplasia. The pancreatic proteins were not seen in other cells in the distal oesophagus. CONCLUSION: Pancreatic acinar-like metaplasia is common in the distal oesophagus and pancreatic secretory proteins, including trypsininogen 2, are produced in the oesophageal metaplastic acinar cells. The biological significance of this finding has yet not been thoroughly studied.

Adolescent↗

Clinical study of chronic pancreatitis with focal irregular narrowing of the main pancreatic duct and mass formation: comparison with chronic pancreatitis showing diffuse irregular narrowing of the main pancreatic duct.

INTRODUCTION: Main pancreatic duct (MPD)-narrowed chronic pancreatitis (CP) may be an autoimmune abnormality. It also has been called autoimmune pancreatitis and sclerosing pancreatitis. It is unclear whether cases with focal pancreatographic changes are part of the same clinical entity as cases with diffuse MPD changes. AIM AND METHODOLOGY: We reviewed seven cases of chronic pancreatitis (CP) with focal narrowing of the main pancreatic duct (MPD), evidenced by endoscopic retrograde cholangiopancreatography (ERCP), and swelling of one or two segments of the pancreas, evidenced by ultrasonography (US) /computed tomography (CT), and indicated the clinicopathologic features of focal-type MPD-narrowed CP. RESULTS: The patient group comprised six men and one woman, and their age range was 28-75 years, with a mean of 63.7 years. Affected sites were in the head in two patients, the body in one patient, the tail in one patient, and the body and tail in three patients; ERP showed narrowing in six patients and obstruction in one. Stricture of the lower portion of the common bile duct (CBD) that caused obstructive jaundice was shown by ERC in two cases in which the pancreas head was affected. In all six patients, a dynamic study by CT or MRI homogeneously showed delayed enhancement of involved segments of the pancreas. Serum levels of pancreatic enzyme were elevated in five patients, but only one subject had pancreatitis-like epigastric pain. Serological evidence suggestive of autoimmune abnormality was detected in only three patients with hypergammaglobulinemia (> or =2.0 g/dL) or positive titers of antinuclear antibody (ANA; > or =80). Histological assessment was available for five patients, who characteristically had dense lymphocytic or plasmocytic infiltration with severe fibrosis that caused luminal narrowing. The clinical, serologic, and histologic findings as described above were comparable to those for 12 CP patients with diffuse narrowing of the MPD, diagnosed during the same period. Surgical resection was performed in 5 patients, in 2 of whom a similar inflammatory process recurred in the remnant head of the pancreas, whereas pancreatitis no longer developed in the other 3 patients. One patient was initially treated with steroids, with clinical remission, although there was neither hypergammaglobulinemia nor positive ANA. CONCLUSION: These results indicate that CP with focal narrowing of the MPD is part of the same clinical spectrum as CP with diffuse narrowing of the MPD, and whether the distribution is diffuse or focal seems to be related to the stage or the extent of the disease. It is therefore important to recognize the possible existence of this focal variant to avoid unnecessary surgery.

Adult↗

Detection of bacterial infection of the pancreatic ducts in patients with pancreatitis and pancreatic cancer during endoscopic cannulation of the pancreatic duct.

Bacterial infections of the pancreas and bacteremia may occur during episodes of pancreatitis. Detection of bacterial infections of the pancreas in the past has required laparotomy. The present study was undertaken to determine whether bacterial infection of the pancreas occurred during nonsuppurative pancreatitis. During endoscopic cannulation of the main pancreatic duct, secretin was administered intravenously and pancreatic juice aspirated from within the duct was cultured. Bacterial infections were detected in 11 of 35 patients with pancreatitis and 3 of 5 with pancreatic cancer. The pancreatic juice was sterile in 25 controls. Cultures from the common bile duct in 9 controls were also sterile whereas 4 of 6 with pancreatitis showed infected bile. The infecting organisms were principally gram-negative and the infections were usually polymicrobial. Antibiotics, where used, successfully eradicated the infecting organisms but did not appear to affect the patient's clinical course.

Adult↗

Identification of immunoreactive pancreatic stone protein in pancreatic stone, pancreatic tissue, and pancreatic juice.

We first examined whether pancreatic stone protein (PSP) was present in pancreatic stone and normal pancreatic tissue. By using HPLC and Western blotting, a protein of Mr 13.5 kDa that reacted with monoclonal antibody against PSP was detected as a major component in EDTA-soluble fractions of pancreatic stone. In an in vitro experiment, this protein dose-dependently suppressed CaCO3 precipitation. PSP was immunohistochemically stained in the acinar cells of normal pancreatic tissue. Based on these findings, it seemed that PSP in pancreatic stone is probably a physiological secretory protein of the pancreas. We subsequently examined immunoreactive PSP in normal pancreatic juice by the Western blotting method. In all of the specimens, the band for immunoreactive PSP in pancreatic juice was found to correspond to 13.5 kDa, which thus agreed with that of purified PSP from a stone.

Blotting, Western↗

Segmental pancreatic autotransplantation with pancreatic ductal occlusion after near total or total pancreatic resection for chronic pancreatitis. Results at 5- to 54-month follow-up evaluation.

Reported are eight patients with idiopathic chronic pancreatitis and two patients with alcoholic pancreatitis who had near total distal pancreatectomy for disabling pain and underwent simultaneous segmental pancreatic autotransplantation of the body and tail of the gland to the femoral area in an attempt to prevent or delay the onset of diabetes. The median follow-up period was 31 months, and follow-up study in nine patients ranged from 24 to 54 months. Patency of the grafts was determined by angiography and selected percutaneous venous assays for insulin. Islet cell function was determined by oral glucose tolerance tests, intravenous (I.V.) glucose tolerance tests, and I.V. glucagon stimulation studies. Segmental autotransplantation was technically successful in eight patients, only one of whom required insulin (at 2 years after grafting). The other seven patients with technically successful grafts have remained insulin independent, including two patients who later underwent pyloric preserving pancreatoduodenectomy for completion pancreatectomy. Variable pain relief was observed in patients who underwent near total pancreatectomy, but pain was unrelieved in those patients who underwent limited distal resection. Patients with idiopathic pancreatitis appear to have better pain relief and preservation of endocrine function than alcoholic patients. Segmental pancreatic autotransplantation prevents or delays the onset of diabetes mellitus and should be considered as an alternative for those patients who require extensive pancreatic resection for chronic pancreatitis.

Adult↗

Clinical and imaging features of autoimmune pancreatitis with focal pancreatic swelling or mass formation: comparison with so-called tumor-forming pancreatitis and pancreatic carcinoma.

OBJECTIVES: Autoimmune pancreatitis (AIP) with a mass formation or swollen pancreas located in one or two segments of the gland (focal type AIP) has been reported. The aims of this study were to elucidate the relationship of the disease entity between this focal variant and so-called tumor-forming pancreatitis (TFP) and to describe the clinical and imaging features discriminating focal AIP from pancreatic carcinoma (Pca). METHODS: The clinical, radiologic, and pathologic profiles of nine patients with focal AIP were reviewed retrospectively and compared with those of 11 patients with alcohol-induced TFP and 80 patients with Pca. RESULTS: The patients with focal AIP were predominantly older (mean age 64.7 +/- 13.6 yr, range 28-78 yr), male, and presenting with obstructive jaundice or focal pancreatic enlargement accompanied by mild abdominal symptoms. In comparison, the patients with alcohol-induced TFP who were mostly middle-aged (mean age 50.1 +/- 7.95 yr, range 39-62 yr), male, and often had attacks of pancreatitis associated with findings of CT scans showing pseudocysts or peripancreatic effusion. Focal AIP usually demonstrated no abnormalities on pancreatograms downstream from the stricture or obstruction and often presented few contrast-filled side branches in the area of main pancreatic duct (MPD) stenosis. These characteristics were similar to the imaging features of Pca. Significant factors differentiating focal AIP from Pca were lower serum levels of CA19-9, homogeneous delayed enhancement evident in dynamic CT scans, and ERCP findings exhibiting a longer stenosed MPD and a thinner MPD upstream from the stricture. CONCLUSIONS: Focal AIP is associated with clinical and radiologic features that are different from those of alcohol-induced TFP. In TFP there are two causative factors, namely, AIP and alcohol-induced chronic pancreatitis. Differential diagnosis of focal AIP from Pca seems to be possible in many cases by evaluating imaging findings such as dynamic CT and ERCP, although focal AIP sometimes shows clinical and radiologic features similar to those of Pca.

Adult↗

Changes in gene expression of pancreatitis-associated protein and pancreatic secretory trypsin inhibitors in experimental pancreatitis produced by pancreatic duct occlusion in rats: comparison with gene expression of cholecystokinin and secretin.

Pancreatic duct occlusion is known to produce a sustained increase in the plasma cholecystokinin (CCK) concentration and to affect the tissue content of CCK in the rat. The tissue content of CCK is correlated with regenerative changes in the pancreas after pancreatic duct occlusion. In the present study, we examined the changes in mRNA levels of pancreatic secretory trypsin inhibitors (PSTIs), pancreatitis-associated protein (PAP), and amylase in the pancreas in comparison with changes in CCK and secretin mRNA levels in the intestine and the histological changes produced by pancreatic duct ligation. Rats with an internal bile fistula and with obstruction of pancreatic flow were prepared and were sacrificed 1, 3, 7, 10, 14, and 28 days later. Then mRNA levels of CCK, secretin, PSTIs, PAP, and amylase were determined by slot-blot analysis. The CCK mRNA level gradually increased to a peak on day 10, was slightly lower on day 14, and returned to the control level on day 28. The level of secretin mRNA did not change. The mRNA levels of PSTIs increased significantly on day 3 after occlusion. PAP mRNA was detectable on days 1 and 3, being maximal on day 1. The mRNA level of amylase was markedly decreased on days 1 and 3, then remained lower than the control level. Histological examination showed acute inflammatory changes in the pancreas on days 1 and 3 and regenerative changes from day 7. These results suggest that a change in gene expression of PAP reflects acute inflammatory changes in the pancreas most sensitively.

Acute-Phase Proteins↗

Comparative evaluation of a high lipase pancreatic enzyme preparation and a standard pancreatic supplement for treating exocrine pancreatic insufficiency in chronic pancreatitis.

OBJECTIVE: To compare the efficacy and safety of two enzyme-containing preparations, Pancrease HL (Cilag) containing 25,000 units of lipase per capsule and Creon (Triosol) with 8000 units of lipase per capsule, in patients with chronic pancreatitis and exocrine insufficiency. DESIGN: The study is a monocentric open crossover prospective study including 25 patients entered from March 1993 to May 1994. PATIENTS: Chronic pancreatitis was alcohol-related in 23 patients, previous surgery was performed in 9, 16 had diabetes and all had steatorrhoea (fat balance > 10g/24h). METHODS: Patients were investigated during four periods of 2 weeks, each one corresponding to a new treatment regimen: Pancrease HL, 3 capsules/day or Creon, 9 capsules/day, with or without omeprazole 20 mg/day. Stools were collected on the last 3 days at the end of each period when the patients were on a standard diet with a fixed daily intake of 100 g fat/day. RESULTS: Faecal fat, protein and energy excretion did not differ when both preparations were compared at roughly pharmaceutically equivalent doses. No significant improvement in fat and protein absorption was observed when omeprazole was taken with the pancreatic enzymes. However, omeprazole treatment was associated with a marked decrease in the fat-protein content ratio, suggesting an improvement in the fat digestive process but a decrease in the efficiency of protein digestion. Drug safety was comparable in the four groups of treatment. CONCLUSION: Pancrease HL with high lipase activity provides effective pancreatic enzyme replacement therapy in patients with chronic pancreatitis at an appreciably lower number of capsules per day than with standard preparations.

Cross-Over Studies↗

Hereditary pancreatitis and the risk of pancreatic cancer. International Hereditary Pancreatitis Study Group.

BACKGROUND: Hereditary pancreatitis is an autosomal-dominant disease, with a variable expression and an estimated penetrance of 80%. The gene for this disease has recently been mapped to chromosome 7q35, and the defect is believed to be caused by a mutation in the cationic trypsinogen gene. Acute attacks of abdominal pain begin early in life and the disease often progresses to chronic pancreatitis. Although the risk of pancreatic cancer is thought to be increased in more common types of chronic pancreatitis, the frequency of pancreatic cancer in the inherited type of pancreatitis is uncertain. PURPOSE: The aim of this study was to assess the frequency of pancreatic cancer and other tumors in patients with hereditary form of pancreatitis. METHODS: To determine the natural history of hereditary pancreatitis, we invited all members of the American Pancreatic Association and the International Association of Pancreatology to participate in a longitudinal study of this rare form of pancreatitis. The initial criteria for patient eligibility were as follows: early age (< or = 30 years) at onset of symptoms, positive family history, and absence of other causes. From April 1995 through February 1996, 37 physicians from 10 countries contributed medical records of 246 (125 males and 121 females) patients thought to have hereditary pancreatitis as the most likely diagnosis. This group included 218 patients where the diagnosis appeared to be highly probable and 28 additional patients where the diagnosis of hereditary pancreatitis was less certain: 25 patients who had relatively late onset of disease and a positive family history and three patients with onset of disease before age 30 years but with an uncertain family history. We reviewed all causes of death and compared the observed to the expected frequency of cancer in this historical cohort of patients with hereditary pancreatitis. The strength of the association between pancreatitis and pancreatic cancer was estimated by the standardized incidence ratio (SIR), which is the ratio of observed pancreatic cancer cases in the cohort to the expected pancreatic cancers in the background population, adjusted for age, sex, and country. RESULTS: The mean age (+/- standard deviation [SD]) at onset of symptoms of pancreatitis was 13.9 +/- 12.2 years. Compared with an expected number of 0.150, eight pancreatic adenocarcinomas developed (mean age +/- SD at diagnosis of pancreatic cancer: 56.9 +/- 11.2 years) during 8531 person-years of follow-up, yielding an SIR of 53 (95% confidence interval [CI] = 23-105). The frequency of other tumors was not increased: SIR = 0.7 (95% CI = 0.3-1.6). Eight of 20 reported deaths in the cohort were from pancreatic cancer. Thirty members of the cohort have already been tested for the defective hereditary pancreatitis gene: all 30 carry a mutated copy of the trypsinogen gene. The transmission pattern of hereditary pancreatitis was known for 168 of 238 patients without pancreatic cancer and six of eight with pancreatic cancer. Ninety-nine of the 238 patients without pancreatic cancer and six of the patients with pancreatic cancer inherited the disease through the paternal side of the family. The estimated cumulative risk of pancreatic cancer to age 70 years in patients with hereditary pancreatitis approaches 40%. For patients with a paternal inheritance pattern, the cumulative risk of pancreatic cancer is approximately 75%. CONCLUSIONS: Patients with hereditary pancreatitis have a high risk of pancreatic cancer several decades after the initial onset of pancreatitis. A paternal inheritance pattern increases the probability of developing pancreatic cancer.

Adolescent↗

Values of CA 19-9 in the serum, pure pancreatic juice, and aspirated pancreatic material in the diagnosis of malignant pancreatic tumor.

The diagnostic accuracy of the measurement of CA 19-9 in the serum, pure pancreatic juice, and aspirated pancreatic fluid in the diagnosis of pancreatic tumors was assessed in 32 patients with malignant pancreatic tumors and 19 patients with pancreatitis. Pure pancreatic juice was collected from the pancreatic duct by endoscopic cannulation with a duodenofiberscope after intravenous administration of secretin. Pancreatic material was obtained by percutaneous fine-needle aspiration biopsy under ultrasonic guidance. Abnormally high CA 19-9 levels in the serum were significantly more frequent in patients with malignant pancreatic tumors than in those with pancreatitis: they were elevated in 71.9% of the patients with pancreatic tumors. High CA 19-9 levels were found primarily in patients with a tumor of the head of the pancreas, in those with a tumor greater than 3 cm in its greatest diameter, and in those with an unresectable cancer. Only 57.1% of seven patients with a tumor of less than 3 cm in its greatest diameter showed an increase in CA 19-9 level. The CA 19-9 levels in pure pancreatic juice were significantly higher in patients with pancreatic tumors than in patients with pancreatitis without pancreatic stone. However, it was not useful for differentiating pancreatic tumors from pancreatitis with pancreatolithiasis. The CA 19-9 level in pancreatic materials obtained by aspiration biopsy was significantly higher in patients with malignant pancreatic tumors than in those with pancreatitis. Eight patients (80%) with pancreatic tumors had values above 1000 U/ml, whereas all five patients with pancreatitis had values of less than 30 U/ml. Although CA 19-9 levels in pancreatic materials was useful only when cytologic examination did not provide any evidence of malignancy, the combination of the CA 19-9 assay and the cytologic study of specimens obtained by percutaneous fine-needle aspiration biopsy of the pancreas increased the diagnostic rate to 100%.

Adult↗

Correlation between pancreatic endocrine and exocrine function and characteristics of pancreatic endocrine function in patients with diabetes mellitus owing to chronic pancreatitis.

CONCLUSION: Pancreatic endocrine capacities are remarkably disturbed in patients with pancreatic diabetes owing to calcific pancreatitis as opposed to those owing to noncalcific pancreatitis. Insulin secretion in calcific pancreatitis resembled that in insulin-dependent diabetes mellitus (IDDM), whereas insulin secretion in noncalcific pancreatitis resembled that in non-IDDM (NIDDM). The involvements of acinar cell and ductal cell function closely correlate with endocrine function (insulin and glucagon secretions) in chronic pancreatitis (pancreatic diabetes). BACKGROUND: We sought to clarify the differences of pancreatic endocrine function between pancreatic diabetes and primary diabetes, and to verify the correlations between pancreatic exocrine and endocrine dysfunction in patients with chronic pancreatitis. METHODS: Urinary C-peptide (CPR) excretion and fasting plasma glucagon levels in patients with pancreatic diabetes owing to calcific pancreatitis (19 cases) and owing to noncalcific pancreatitis (14 cases) were studied in comparison with those in patients with insulin-dependent diabetes mellitus (IDDM, 23 cases), noninsulin-dependent diabetes (NIDDM, 18 cases), and in healthy controls (11 cases). In addition, pancreatic exocrine function was investigated in patients with chronic pancreatitis (calcific and noncalcific) and in healthy controls. The correlation between pancreatic exocrine and endocrine function was studied. RESULTS: The urinary CPR excretion in controls was 94.9 +/- 20.5 micrograms/d. The urinary CPR excretion in calcific pancreatitis was 12.8 +/- 7.4 micrograms/d and it resembled that in IDDM (9.4 +/- 5.8 micrograms/d). The urinary CPR excretion in noncalcific pancreatitis was 41.5 +/- 30.1 micrograms/d, being similar to that in NIDDM (49.3 +/- 21.0 micrograms/d). The plasma glucagon level in calcific pancreatitis was 64.1 +/- 15.9 rho g/mL, which was significantly lower than the values in IDDM (111.2 +/- 50.2 rho g/mL) and NIDDM (96.7 +/- 21.9 rho g/mL). The plasma glucagon level in calcific and noncalcific pancreratitis (88.4 +/- 29.6 rho g/mL) were significantly lower than that in controls (129.8 +/- 21.6 rho g/mL). The residual capacities of acinar cells and ductal cells were strongly correlated with urinary CPR excretion and plasma glucagon concentration.

Adult↗

Molecular profiling of pancreatic adenocarcinoma and chronic pancreatitis identifies multiple genes differentially regulated in pancreatic cancer.

The molecular basis of pancreatic cancer is not understood. Previous attempts to determine the specific genes expressed in pancreatic cancer have been hampered by similarities between adenocarcinoma and chronic pancreatitis. In the current study, microarrays (Affymetrix) were used to profile gene expression in pancreatic adenocarcinoma (10), pancreatic cancer cell lines (7), chronic pancreatitis (5), and normal pancreas (5). Molecular profiling indicated a large number of genes differentially expressed between pancreatic cancer and normal pancreas but many fewer differences between pancreatic cancer and chronic pancreatitis, likely because of the shared stromal influences in the two diseases. To specifically identify genes expressed in neoplastic epithelium, we selected genes more highly expressed (>2-fold, p < 0.01) in adenocarcinoma compared with both normal pancreas and chronic pancreatitis and which were also highly expressed in pancreatic cancer cell lines. This strategy yielded 158 genes, of which 124 were not previously associated with pancreatic cancer. Quantitative-reverse transcription-PCR for two molecules, S100P and 14-3-3sigma, validated the microarray data. Support for the success of the neoplastic cell gene expression identification strategy was obtained by immunocytochemical localization of four representative genes, 14-3-3sigma, S100P, S100A6, and beta4 integrin, to neoplastic cells in pancreatic tumors. Thus, comparisons between pancreatic adenocarcinoma, pancreatic cancer cell lines, normal pancreas, and chronic pancreatitis have identified genes that are selectively expressed in the neoplastic epithelium of pancreatic adenocarcinoma. These data provide new insights into the molecular pathology of pancreatic cancer that may be useful for detection, diagnosis, and treatment.

Adenocarcinoma↗

Surgical treatment for chronic pancreatitis: results of pancreatic duct drainage operation and pancreatic resection.

Between 1978 and 1999, 86 patients with chronic pancreatitis were surgically treated at the Surgical Department of Kurume University Hospital. Of these patients, 30 were treated by pancreatic duct drainage operation (drainage operation), while 40 were treated by pancreatic resection, and the results were compared between the two groups. In patients who underwent drainage operation, pain disappeared in 85.7%, slightly relieved in 10.7%, and not relieved in 3.6%. In patients who underwent pancreatic resection, pain disappeared in 73.4%, slightly relieved in 13.3%, and not relieved in 13.3%. Therefore, there was no significant difference in the pain-relieving effect between the two groups. However, the pain-relieving effect was poorer in patients who underwent pancreatic resection than in those who underwent drainage operation. In addition, all patients who showed poor results for pain relief had alcoholic pancreatitis. Endocrine and exocrine functions of the pancreas were improved in 6, maintained in 2, and exacerbated in 4 patients who underwent drainage operation. In patients who underwent pancreatic resection, endocrine and exocrine function of the pancreas were improved in 3, maintained in 3, and exacerbated in 13. Therefore, endocrine and exocrine function of the pancreas were poorer in patients who underwent pancreatic resection than in those who underwent drainage operation. Distant results in patients who underwent drainage operation were good in 75.0%, fair in 15.0%, and poor in 10.0%. In patients who underwent pancreatic resection, distant results were good in 80.0%, fair in 13.3%, and poor in 6.7%. Therefore, favorable distant results were obtained in both groups. These findings suggest that surgical techniques that preserve functions of the pancreas should be selected during surgical treatment for chronic pancreatitis. We consider that the presence or absence of main pancreatic duct dilation and the site of pancreatic lesions are important indices for selecting surgical techniques. Therefore, drainage operation consisting of pancreaticojejunostomy should be indicated for patients with main pancreatic duct dilation, while pancreatic resection should be indicated for those without main pancreatic duct dilation, those with localized pancreatic lesions, and those with suspected pancreatic cancer.

Adult↗

Lysosomal enzyme secretion into pancreatic juice in rats injected with pancreatic secretagogues and augmented secretion after short-term pancreatic duct obstruction.

To examine the possible secretion of lysosomal enzymes into the pancreatic juice in rats stimulated with pancreatic secretagogues under both physiological and pathological conditions, we investigated the changes in the secretion of cathepsin B, as a lysosomal enzyme, into pancreatic juice with stimulation of 5 different doses (0.1, 0.2, 0.5, 1.0, and 1.5 micrograms/kg.hr) of caerulein. Control rats had only pancreatic duct cannulation. In other rats, the pancreatic duct was obstructed for 3 hours and secretin was infused (0.2 CU/kg.hr). Caerulein stimulated the secretion of cathepsin B into the pancreatic juice in a dose-dependent manner, as in amylase secretion, and caerulein in higher doses (1.0 and 1.5 microgram/kg.hr) inhibited cathepsin B output as it did amylase output. There was a significantly high positive correlation between cathepsin B output and amylase output after stimulation with caerulein. The secretion of several other lysosomal enzymes was also stimulated by caerulein. Blockage of the pancreatic duct for 3 hours caused a significant but moderate rise in serum amylase levels. Redistribution of cathepsin B activity in the pancreatic subcellular fractions was noted with an increase in the amount of cathepsin B recovered from zymogen-rich pellets after 15 min of centrifugation at 1300 x g. These changes after temporary pancreatic duct obstruction are very similar to those previously noted during the early stage of diet-and caerulein-induced experimental pancreatitis and suggest colocalization of lysosomal enzymes and digestive enzymes. In addition, in duct obstructed rats, the secretion of cathepsin B and other lysosomal enzymes stimulated by caerulein was significantly greater than in animals with free-flowing pancreatic juice. These results indicate that lysosomal enzymes are secreted into pancreatic juice after stimulation by gut hormones in the same manner as classical pancreatic digestive enzymes such as amylase. Moreover, lysosomal enzymes which colocalize with zymogen granules in rats with short-term pancreatic duct obstruction are also secreted into pancreatic juice together with digestive enzymes after stimulation with gut hormones. These findings suggest that lysosomal enzymes are present in zymogen granules under normal conditions and that they may play pathophysiological roles in pancreatic juice. They also contribute to an understanding of the pathogenesis of pancreatitis, since cathepsin B can activate trypsinogen.

Amylases↗

Comparison of pancreatic dysfunction in chronic alcoholic pancreatitis and chronic gallstone pancreatitis.

Comparative assessments of the endocrine and exocrine functions of the pancreas associated with gallstone pancreatitis or alcoholic pancreatitis were performed in a series of 86 patients, 20 with cholelithiasis, 12 with chronic alcoholism, 24 with chronic gallstone pancreatitis and 30 with chronic alcoholic pancreatitis and 32 healthy subjects were served as controls. The patients with cholelithiasis showed exocrine hypersecretion of the pancreas. In the patients with gallstone pancreatitis, all the assessed parameters of exocrine function were depressed. On the other hand, no pancreatic exocrine dysfunction was dispalyed in cases with chronic alcoholism. In the non-calcifying alcoholic pancreatitis, both the volume output and the the maximum concentration and output of bicarbonate were diminished but depression in amylase output was not seen. All these parameters were lowered in patients with calcifying pancreatitis. Elevation of hexosamine concentration in the pancreatic juice was evident in alcoholic pancreatitis as compared with gallstone pancreatitis, being particularly prominent in cases of non-calcifying pancreatitis. Patients with alcoholic pancreatitis were observed to secrete viscous pancreatic juice richer in amylase and hexosamine content, than those in the patients with gallstone pancreatitis. Endocrine dysfunction of the pancreas is more frequent and intense in alcoholic pancreatitis than in gallstone pancreatitis.

Alcoholism↗

Chromosomal instability in pancreatic ductal cells from patients with chronic pancreatitis and pancreatic adenocarcinoma.

Pancreatic adenocarcinoma is a disease with high mortality for which chronic pancreatitis confers a markedly increased risk. We hypothesize that chromosome instability and genomic damage occur in pre-neoplastic pancreatic ductal epithelium, and that this damage may be related to oxidative stress. We used dual-color fluorescence in situ hybridization with centromere probes and locus-specific arm probes for chromosome arms 11q, 17p, and 18q to identify genomic instability in cultures of normal-appearing human pancreatic ductal epithelium from normal organ donor controls compared to patients with chronic pancreatitis or pancreatic adenocarcinoma. To examine early pancreatic tumorigenesis, we studied only normal-appearing pancreatic ductal cells adjacent to pancreatitis or carcinoma. We found that, compared to the finding in normal controls, chromosomal abnormalities are present in normal-appearing human pancreatic ductal epithelia obtained from patients with chronic pancreatitis or pancreatic adenocarcinoma. Furthermore, these chromosomal abnormalities could be induced in cultured pancreatic ductal epithelium from normal organ donors by chronic exposure to dilute hydrogen peroxide, suggesting that oxidative stress may contribute to the development of chromosomal instability in the pancreas. These results elucidate a potential mechanism linking chronic pancreatitis to pancreatic cancer and suggest that chromosomal instability may be an early event in the pathogenesis of pancreatic cancer.

Adenocarcinoma↗