The splice-pattern of CD44 is altered in chronic pancreatitis exhibiting dysplastic changes

Recent studies have shown that several splice variants of CD44, might be involved in tumor progression. Since chronic pancreatitis is suggested to be a risk factor for pancreatic cancer we investigated the splice pattern of CD44 in chronic pancreatitis to elucidate the role of CD44 in pancreas tumorigenesis. The expression of CD44-isoforms was examined in 40 specimens of chronic pancreatitis and 12 specimens of normal pancreas by immunohistochemistry, Westernblotting and exon specific RT-PCR. Pancreatic cancer tissue from two patients who developed pancreatic cancer 2 and 3 years following surgery for chronic pancreatitis were analyzed. Strong expression of CD44s was found in all cells, whereas the expression of CD44v6 was restricted to ductal cells. Westernblotting revealed an overexpression of CD44v6 in chronic pancreatitis as compared to normal pancreas. Exon specific analysis revealed an altered splice pattern of CD44, similar to that in pancreatic cancer, in 12.5% of the chronic pancreatitis specimens. Both patients who developed pancreatic cancer after chronic pancreatitis exhibited this altered splice pattern in both, chronic pancreatitis and pancreatic cancer. These results suggest that variant forms of CD44-mRNA might be expressed in early dysplastic alterations in chronic pancreatitis.     

Chronic pancreatitis is associated with increased concentrations of epidermal growth factor receptor, transforming growth factor alpha, and phospholipase C gamma

The epidermal growth factor (EGF) receptor is a transmembrane protein that binds EGF and transforming growth factor alpha (TGF alpha), and that stimulates phospholipase C gamma 1 (PLC gamma 1) activity. In this study the role of the EGF receptor in chronic pancreatitis was studied. By immunohistochemistry, the EGF receptor, TGF alpha, and PLC gamma 1 were found to be expressed at high concentrations in pancreatic ductal and acinar cells from chronic pancreatitis patients. Northern blot analysis showed that, by comparison with normal controls, 19 of 27 chronic pancreatitis tissues exhibited a 5.7-fold increase in EGF receptor mRNA concentrations, and 20 of 27 chronic pancreatitis tissues exhibited a sixfold increase in TGF alpha mRNA concentrations. In situ hybridisation confirmed that overexpression occurred in ductal and acinar cells, and showed that both mRNA moieties colocalised with their respective proteins. These findings suggest that TGF alpha may act through autocrine and paracrine mechanisms to excessively activate the overexpressed EGF receptor in the two major cell types of the exocrine pancreas, thereby contributing to the pathobiology of this disorder.     

Plasma alpha 2-macroglobulin-trypsin complexlike substance (MTLS) in pancreatic disease

alpha 2-macroglobulin-trypsin complexlike substance (MTLS) was determined in plasma of pancreatic and nonpancreatic diseases using a two-step enzyme immunoassay to study the diagnostic and pathophysiological significance of MTLS. Plasma levels of MTLS in acute pancreatitis (mean +/- SD = 265.6 +/- 346.2 ng/ ml, n = 9), calcified chronic pancreatitis (128.6 +/- 257.4, n = 13), and noncalcified chronic pancreatitis (13.5 +/- 12.5, n = 10) were significantly higher than that in controls (3.6 +/- 1.8, n = 81). In other diseases such as gastric cancer, hepatoma, diabetes mellitus, and gallstones, MTLS values were not different from those of control. Plasma MTLS values showed low correlation with serum trypsin, elastase 1, pancreatic amylase, lipase, and pancreatic secretory trypsin inhibitor (PSTI). The elevation of plasma MTLS values in acute pancreatitis suggests that plasma MTLS levels reflect that protease is inappropriately activated in pancreatic acinar cell and released into the circulation and that the determination of MTLS can be useful for diagnosis and pathophysiology of acute pancreatitis and chronic pancreatitis.     

Early ductal decompression prevents the progression of biliary pancreatitis: an experimental study in the opossum

BACKGROUND: The value of early endoscopic or surgical interventions to remove bile duct stones and decompress the biliopancreatic ductal system in gallstone pancreatitis is controversial. METHODS: To evaluate this issue, acute hemorrhagic necrotizing pancreatitis was induced in opossums by obstructing the biliopancreatic ductal system with a balloon catheter for 1, 3, or 5 days. RESULTS: A progressive increase in the severity of pancreatitis, as manifested by inflammation, fat necrosis, hemorrhage, acinar cell vacuolization, in vitro lactate dehydrogenase release, and acinar cell necrosis, was noted in these obstructed animals. In contrast, decompression of the obstructed ductal system by removal of the balloon catheter after 1 or 3 days prevented the increase in severity of these parameters of pancreatic injury. CONCLUSIONS: We concluded that the severity of biliary pancreatitis in this model is dependent upon the duration of ductal obstruction and that decompression of the ductal system can prevent progression of the disease. These observations support the practice of early attempts to remove obstructing stones in clinical gallstone pancreatitis.     

Basic principles of surgical policy in complicated chronic pancreatitis

The paper presents some experience with surgical treatment of 183 patients with complicated forms of chronic pancreatitis. The type of a surgical intervention depended on the pattern of pancreatic morphological changes. Operations of internal drainage of the pancreas in 103 patients with ductal hypertension provide the largest percentage (92.4%) of good and satisfactory results. Resectional methods of surgical treatment for chronic pancreatitis (n = 36) without signs of intraductal hypertension and with the prevalence of predominant lesions in some portions of the gland yield 80% good and satisfactory results. The incidence of postoperative complications following pancreatic resections is higher than those after drainages (16.2 versus 11.6%). The paper gives a concept of combined operations on the pancreas and bile ducts in chronic pancreatitis complicated by stricture of the distal common bile duct, revealed in 24.4% of cases.     

Enhanced urokinase plasminogen activation in chronic pancreatitis suggests a role in its pathogenesis

BACKGROUND & AIMS: Urokinase plasminogen activator (uPA) regulates plasmin generation from plasminogen. The aim of this study was to analyze the role of the plasminogen activator/plasmin system in chronic pancreatitis (CP). METHODS: Using Northern blot analysis, in situ hybridization, and immunohistochemistry, the expression of uPA, its receptor (uPAR), plasminogen activator inhibitor 1 (PAI-1), and transforming growth factor beta 1 (TGF-beta 1) was studied in 14 patients undergoing pancreatic resection for CP. Normal control pancreatic tissue was obtained through an organ donor program. RESULTS: Eight of 14 CP samples showed concomitant increased expression (P < 0.001) of uPA (5.2-fold), uPAR (5.9-fold), and TGF-beta 1 (8.8-fold) messenger RNA (mRNA) compared with normal controls. PAI-1 mRNA expression was increased (6.5-fold; P < 0.001) in all CP samples. By in situ hybridization, moderate to strong mRNA staining of all four factors was present in acinar cells, some ductal cells, and areas with ductal metaplasia in CP samples. A similar staining pattern was found by immunohistochemistry. Intense mRNA and immunostaining for all of these factors in CP samples was associated with a higher degree of pancreatic damage. CONCLUSIONS: uPA and its receptor may contribute to the lytic damage observed in CP by plasmin generation. Similarly, increased amounts of plasmin may activate latent TGF-beta, thereby leading to the accumulation of fibrotic tissue.     

The risk of pancreatic cancer following pancreatitis: an association due to confounding?

BACKGROUND & AIMS: Chronic pancreatitis has been suggested as a causal risk factor for pancreatic cancer in a recent study. The aim of this study was to clarify the relationship between chronic pancreatitis and pancreatic cancer. METHODS: All patients in the Swedish inpatient Register with a discharge diagnosis of pancreatitis from 1965 to 1983 were identified. They were stratified into subcohorts as follows: (1) one episode of unspecified pancreatitis (n = 823); (2) one episode of acute pancreatitis (n = 24,753); (3) recurrent pancreatitis (n = 7328); and (4) chronic pancreatitis (n = 4546). We also identified those with associated diagnoses indicating gallbladder disease or alcoholism. The patients were followed up through record linkage to the nationwide Swedish Cancer Register, Death Register, and Migration Register. RESULTS: After exclusion of cancers occurring in the first year, there were excess risks for pancreatic cancer in all subcohorts. However, the risks declined with time in all subcohorts. A persistent excess risk after 10 years was restricted to patients with associated alcohol abuse (standardized incidence ratio, 3.8; 95% confidence interval, 1.5-7.9). CONCLUSIONS: The findings are not consistent with reports that pancreatitis is causally associated with a long-term risk of pancreatic cancer. Selection bias, alcohol consumption, and smoking may contribute to some of the patterns of risk that have been observed.     

Absence of K-ras mutations in the pancreatic parenchyma of patients with chronic pancreatitis

BACKGROUND: Human pancreatic cancers exhibit a high frequency of K-ras mutations. METHODS: In this study we used oligonucleotide specific hybridization to compare the frequency of K-ras mutations in genomic DNA samples prepared from 21 normal pancreatic tissues, 26 chronic pancreatitis tissues, and 24 pancreatic cancers. RESULTS: None of the DNA samples from normal or chronic pancreatitis tissues exhibited a K-ras mutation at codons 12 or 13 of K-ras. In contrast, 17 of 24 DNA pancreatic cancers harbored a K-ras mutation. Validity of the methodology was confirmed by genotyping 7 human pancreatic cancer cell lines. Analysis of focal areas of proliferation from 5 chronic pancreatitis and 5 pancreatic cancer samples processed by selective ultraviolet radiation fractionation (SURF), a procedure used to enrich DNA isolation from foci of proliferating cells, revealed complete concordance with total genomic DNA analysis. CONCLUSIONS: These findings indicate that the pancreatic parenchyma in patients with chronic pancreatitis most frequently does not possess a K-ras mutation.     

Effects of glycosaminoglycans on the glomerular changes induced by Adriamycin

BACKGROUND: A model of moderate acute necrotizing pancreatitis is essential for the study of the pathophysiology of the disease and novel therapies. We tried to establish a model of bile salt-induced acute necrotizing pancreatitis in rats. METHODS: Acute pancreatitis was induced by retrograde infusion of bile salt into the cannulated pancreatobiliary duct. Twenty-six rats wee divided into 3 groups. Group I (n = 8) received 0.2 ml of glycodeoxycholic acid (GDOC) 10 mmol/l; group II (n = 10) 0.2 ml of 2.5% sodium taurodeoxycholate (NaTDC); group III (n = 8) the mixture of 0.2 ml GDOC 10 mmol/l and 10 U enterokinase. Serum levels of amylase and lipase, hematocrit, mean arterial pressure and heart rate were determined at baseline and 5 hours later. Then the pancreas was removed for histopathology and grading (0-3; absent-severe) with regard to leukocyte infiltration, edema, necrosis, hemorrhage and acinar cell vacuolization. RESULTS: Serum levels of amylase and lipase increased significantly in 5 hours in all the groups. Serum amylase levels were significantly lower in group III than in group II. No significant difference of serum lipase was found among the groups. Group II had the highest scores of necrosis and acinar cell vacuolization, whereas group III had the highest scores of leukocyte infiltration and edema. The degree of necrosis was significantly more severe in group II than in group I. The hematocrit increased significantly in 5 hours in groups I and II. The mean arterial pressure in 5 hours decreased significantly in group I. There was no significant difference of the changes of heart rate in 5 hours among 3 groups. CONCLUSIONS: Intraductal infusion of NaTDC was a good method to induce moderate acute necrotizing pancreatitis in rats. GDOC caused mild pancreatitis, and pancreatic injury was aggravated when enterokinase was added. The severity of pancreatic histopathology was not correlated with the changes of serum levels of pancreatic enzymes, hematocrit or mean arterial pressure at the early stage of pancreatitis.     

Ultrastructural studies of experimental acute pancreatitis

Acute pancreatitis was studied by electron microscopy after retrograde infusion of either trypsin, and/or beta-glucuronidase into the canine pancreatic duct. Marked changes were induced by the mixture of trypsin and beta-glucuronidase. (1) The acinar cells were initially excavated from the acinar lumen and formed cystic bodies in themselves. The cystic bodies were then disrupted at their marginal membranes, and the acinar cells were filled with a large amount of fibrillar materials which originated from the contents of the cystic bodies. At this time, the luminal margin of the acinar cells completely disappeared. (2) The cellular organellas and the intracellular fibrillar materials in the acinar cells were discharged into the interstitial space through the disrupted basal lamina. Infection in the pancreatic ductal system was considered to play an important role in the pathogenesis of acute hemorrhagic pancreatitis.     

CD8+CD103+ T cells analogous to intestinal intraepithelial lymphocytes infiltrate the pancreas in chronic pancreatitis

OBJECTIVE: Chronic pancreatitis is a painful chronic inflammatory disease of the exocrine pancreas that is associated with the replacement of functional parenchyma by extended fibrosis and with a massive infiltration of T lymphocytes. However, to date further characterization of infiltrating T cells in chronic pancreatitis has not been undertaken. METHODS: Using the novel method of multiepitope imaging with fluorochrome-tagged specific monoclonal antibodies, which allows the simultaneous localization and characterization of T cells in tissues, we analyzed the distribution and phenotypes of T cells infiltrating the pancreas in chronic pancreatitis. RESULTS: The mean CD4:CD8 ratio in 10 cases of chronic pancreatitis was 2.4:1. In order of decreasing frequency, the following markers were observed: CD45RO, CD18, TCRgammadelta, and CD103. The lymphocytes, especially of the CD4+ subset, were found mainly in the fibrous stroma, but T cells were also observed periductally. A T-cell subset bearing the phenotype CD8+CD103+, analogous to intestinal intraepithelial lymphocytes, was found intracalating between the cells of the ductal epithelium. CONCLUSIONS: Phenotyping of the T lymphocytes in chronic pancreatitis supports the concept of the involvement of cell-mediated cytotoxicity in the pathogenesis of this disease. In addition, intraepithelial lymphocytes were found interspersed between the ductal epithelial cells, pointing to a role of this T-cell subset as a first-line defense against deleterious epithelial events in chronic pancreatitis.     

Nonductal tumors of the pancreas. The importance of laparotomy

OBJECTIVES: To delineate the incidence of nonductal pancreatic neoplasms and determine whether distinguishing clinical or radiologic characteristics exist. METHODS: From 1977 through 1990, we examined 353 patients with a pancreatic mass as demonstrated on abdominal computed tomography or ultrasonography. Patients with chronic pancreatitis or functioning neuroendocrine tumors were excluded. All patients underwent operative exploration for histopathologic diagnosis and resection when possible. RESULTS: Adenocarcinoma of the pancreas was seen in 322 patients. The remaining 31 patients (8.8%) were found to have nonductal tumors of the pancreas, including nonfunctioning islet cell tumors (15), cystadenoma (nine), lymphoma (five), lipoma (one), and mesothelioma (one). These neoplasms were evenly distributed between the head and tail of the pancreas, while most of the ductal pancreatic carcinomas were located in the pancreatic head. While abdominal computed tomography and ultrasonography accurately identified most cystic neoplasms, the remaining nonductal lesions were indistinguishable from ductal pancreatic tumors. Preoperative biochemical studies and liver function tests failed to separate ductal and nonductal pancreatic masses. Average survival for patients with nonductal lesions was significantly longer compared with ductal tumors of the pancreas. CONCLUSIONS: Because increasing reliance on advanced radiologic and invasive nonoperative diagnostic testing may deny proper surgical therapy to patients with nonductal neoplasms of the pancreas, laparotomy and histopathologic diagnosis are advisable in most patients with an isolated pancreatic mass.     

MR pancreatography: a useful tool for evaluating pancreatic disorders

Magnetic resonance (MR) pancreatography is being used with increasing frequency as a noninvasive alternative to diagnostic endoscopic retrograde pancreatography in the evaluation of the pancreatic duct and various pathologic conditions of the pancreas. This recently developed technique allows improved spatial resolution and permits imaging of the entire pancreatico-biliary tract during a single breath hold. MR pancreatography can help identify the course and drainage pattern of the pancreatic duct and is useful in diagnosing congenital anomalies such as pancreas divisum and annular pancreas without the risk of inducing pancreatitis. In some instances, MR pancreatography may demonstrate duct disruption and associated fluid collections resulting from trauma. In recurrent acute pancreatitis, MR pancreatography is useful in suggesting the cause of the disease; in chronic pancreatitis, it is useful in depicting ductal anatomy, detecting strictures or intraductal calculi prior to surgery, and detecting complications such as pseudocysts and fistulas. In addition, MR pancreatography performed in conjunction with abdominal MR imaging is useful in identifying pancreatic malignancies as well as in establishing resectability and preventing unnecessary preoperative stent placement.     

Effect of recombinant platelet-activating factor acetylhydrolase on two models of experimental acute pancreatitis

BACKGROUND & AIMS: Recent reports suggest that platelet-activating factor (PAF) plays a role in pancreatitis and pancreatitis-associated lung injury. In this study, the effects on these processes of termination of PAF action by recombinant PAF-acetylhydrolase (rPAF-AH) were investigated. METHODS: Rats were given rPAF-AH and then infused with a supramaximally stimulating dose of cerulein to induce mild pancreatitis. Opossums underwent biliopancreatic duct ligation to induce severe pancreatitis, and rPAF-AH administration was begun 2 days later. RESULTS: In mild, secretagogue-induced pancreatitis, rPAF-AH given before the cerulein reduced hyperamylasemia, acinar cell vacuolization, and pancreatic inflammation but did not alter pancreatic edema or pulmonary microvascular permeability. In severe, biliopancreatic duct ligation-induced pancreatitis, rPAF-AH delayed and reduced the extent of inflammation and acinar cell injury/necrosis and completely prevented lung injury even though the rPAF-AH administration was begun after the onset of pancreatitis. CONCLUSIONS: PAF plays an important role in the regulation of pancreatic injury but not pancreatic edema or increased pulmonary microvascular permeability in mild, secretagogue-induced pancreatitis. PAF plays a critical role in the regulation of progression of pancreatic injury and mediation of pancreatitis-associated lung injury in severe biliary pancreatitis. Amelioration of pancreatitis and prevention of pancreatitis-associated lung injury can be achieved with rPAF-AH even if treatment is begun after pancreatitis is established.     

Simultaneous determinations of pancreatic phospholipase A2 and prophospholipase A2 in various pancreatic diseases

Pancreatic phospholipase A2 (PLA2) is secreted into the pancreatic juice by pancreatic acinar cells as a proenzyme (proPLA2), which is activated by trypsin. Radioimmunoassays with monoclonal antibodies to PLA2 and proPLA2 were used to examine the serum PLA2 and proPLA2 levels simultaneously in patients with various pancreatic diseases. In healthy subjects, proPLA2 proved to be the major form of the enzyme. The serum PLA2 level were found to be significantly increased in patients with acute pancreatitis, the active phase of chronic relapsing pancreatitis, and the early stage of pancreatic cancer. In the terminal stage of pancreatic cancer the serum PLA2 level became low. In patients with chronic pancreatitis, significant correlations were observed between the levels of factors evaluated by the secretin test and the serum total PLA2 and proPLA2 level, but not the PLA2 level. The serum PLA2 and proPLA2 concentrations, and the proportion of proPLA2 in the total, were within normal ranges in patients with liver cirrhosis, hepatocellular carcinoma, and chronic renal failure. These results suggest that simultaneous measurements of serum PLA2 and proPLA2 are clinically useful for diagnosis and monitoring of the active phase of pancreatitis.     

Peak oxygen uptake and maturation in 12-yr olds

OBJECTIVE: The purpose of this study is to report a new sign, "acinar filling," observed on dynamic MR pancreatography after secretin stimulation in patients with suspected early chronic pancreatitis. CONCLUSION: Acinar filling might reflect tissue hypertension or loss of pancreatic parenchyma compliance or both. This finding is probably an insensitive but specific sign of early chronic pancreatitis.     

Detection of K-ras gene mutations at codon 12 in the pancreatic juice of patients with intraductal papillary mucinous tumors of the pancreas

BACKGROUND: The authors previously found specific mutations of the K-ras gene at codon 12 in the pancreatic juice of 67% of patients (6 of 9) with pancreatic ductal carcinoma, and the detection of these mutations was useful for diagnosis. This study was performed to detect and evaluate K-ras mutations in pancreatic juice from patients with intraductal papillary mucinous tumor of the pancreas, which is considered a low grade malignancy. The results were interpreted from the viewpoint of clinical significance. METHODS: K-ras mutations were examined using seminested polymerase chain reaction analysis combined with restriction enzyme digestion, followed by nonradioisotopic single strand DNA conformation polymorphism. RESULTS: Twelve of thirteen cases (92%) of intraductal papillary mucinous tumor of the pancreas, confirmed histologically (9 adenomas and 4 carcinomas), and 26 of 43 cases (60%) of ductal carcinoma showed specific K-ras gene mutations in the pancreatic juice. Furthermore, 4 of 22 patients (18%) with chronic pancreatitis, followed for more than 1 year without a sign of pancreatic tumor, showed K-ras mutations. In contrast, no mutations of the K-ras gene were detected in the pancreatic juice from 28 normal controls. CONCLUSIONS: K-ras mutations were found in the pancreatic juice of all but one patient with intraductal papillary mucinous tumor of the pancreas, but they were not useful for distinguishing carcinoma from adenoma. The authors concluded that K-ras mutations are not a specific marker for pancreatic neoplasms because similar mutations were detected in the pancreatic juice from patients with chronic pancreatitis. At the present time, the detection of K-ras mutations in pancreatic juice should be used clinically as an adjunct diagnostic modality for pancreatic diseases.     

Prevalence of Helicobacter pylori infection and gastric mucosal abnormalities in chronic pancreatitis

OBJECTIVE: Chronic pancreatitis is often associated with abnormal gastric acid secretion. However, previous studies have taken into consideration neither the potential role of Helicobacter pylori (H. pylori) infection nor histological features of the gastric mucosa in this context. The aim of this study was to analyze the prevalence of H. pylori infection as well as the pattern of gastritis in patients with chronic pancreatitis. METHODS: Forty patients with chronic alcoholic pancreatitis were included in the study: 40 patients with alcoholic liver cirrhosis and normal exocrine pancreatic function and 40 asymptomatic nonalcoholic subjects matched for age and sex used as control subjects. Endoscopy was performed in all patients, and five biopsy specimens from the antrum (three from the gastric body and two from the cardia) were taken for histological grading of gastritis and H. pylori assessment. RESULTS: Prevalence of H. pylori infection was similar in subjects with chronic pancreatitis (38%), asymptomatic subjects (28%) and liver cirrhosis (30%). Topography and expression of H. pylori-associated chronic gastritis was also not different among the three groups of subjects. In H. pylori-negative subjects, the presence of moderate to severe chronic antral gastritis was significantly more common in patients with chronic pancreatitis (40%) than in subjects with liver cirrhosis (18%) and in asymptomatic subjects (14%) (p < 0.05). No difference was found among the three groups of patients with regard to gastritis activity, atrophy, and intestinal metaplasia in the various gastric regions. The chronicity grade of gastritis did not correlate with the severity of pancreatic insufficiency. CONCLUSION: Prevalence of H. pylori infection is not different in patients with chronic pancreatitis as compared with subjects alcoholic liver cirrhosis and asymptomatic subjects. A severe H. pylori-negative chronic gastritis is more common in patients with chronic pancreatitis. This chronic inflammation of the gastric mucosa could contribute to determining the changes in gastric physiology described in patients with chronic pancreatitis.     

Contrast-enhanced endoscopic ultrasonography in pancreatic diseases: a preliminary study

OBJECTIVE: The purpose of this study was to clarify the usefulness of contrast-enhanced endoscopic ultrasonography in pancreatic diseases. METHODS: The subjects comprised 37 patients with pancreatic diseases: 11 with ductal cell carcinoma, 10 with mucin-producing tumor, five with pseudo-cyst, four with islet cell tumor, four with chronic pancreatitis, and three with serous cystadenoma. After endoscopic ultrasonography, Albunex (0.22 ml/kg) was injected intravenously at a rate of 1 ml/s into the right median vein, and observation was continued for 10 min. The presence or absence of enhancement of the lesion was determined in each disease. Because all the patients with ductal cell carcinoma, islet cell tumor, chronic pancreatitis, and serous cystadenoma, as well as five with mucin-producing tumor and three with pseudo-cyst, underwent angiography, vascularity was compared between angiographic images and those of contrast-enhanced ultrasonography. RESULTS: Enhancement of the lesion was observed in all patients with islet cell tumor and serous cystadenoma, in eight with mucin-producing tumor, and in three with chronic pancreatitis. However, no enhancement effect was observed in the patients with ductal cell carcinoma and those with pseudo-cyst. Comparison between the images of contrast-enhanced endoscopic ultrasonography and angiographic images showed three patients in whom angiograms were hypovascular, but enhancement effect was observed on ultrasonographic images. CONCLUSION: The combined evaluation of plain and enhanced images of endoscopic ultrasonography may be useful for the diagnosis of pancreatic diseases.     

Diagnosis of a "hereditary pancreatitis" by the detection of a mutation in the cationic trypsinogen gene

HISTORY AND CLINICAL FINDINGS: A 71-year-old woman was admitted with the suspected diagnosis of pancreatic carcinoma. As a child she had had repeated attacks of abdominal pain of undetermined cause. When aged 48 years she had developed diabetes mellitus. Her now 42-year-old daughter had from the age of 9 years suffered from repeated attacks of acute pancreatitis that had finally led to chronic pancreatitis. The patient's 15-year-old grandchild was having recurrent bouts of abdominal pain. INVESTIGATIONS: Imaging procedures revealed calcifications in the pancreas and an infiltrating space-occupying lesion, about 3 cm in diameter, in the head of the pancreas with lymph node and liver metastases. Cytological analysis of material aspirated from the space-occupying mass showed typical findings of ductal pancreatic carcinoma. FURTHER TESTS, TREATMENT AND COURSE: At first the patient's course was not typical for a genetically-determined disease, but the family history raised the suspicion of hereditary pancreatitis. A genetic test (Afl-III-RFLP test) demonstrated the mutation Arg 117 His in the cationic trypsinogen gene in all diseased or symptomatic family members. The patient died of the complications of the pancreatic cancer. CONCLUSION: Genetic tests are valuable in the diagnosis of hereditary pancreatitis, because the increased cancer risk can be met by frequent examinations in affected family members.