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.     

Lung changes by experimentally induced cholesterol atheromatosis (author''s transl)

A family study was prompted by the presence of benign recurrent intrahepatic cholestasis in three members and probably in a fourth. Pruritus and/or jaundice occurred during pregnancy in nine members. Two additional members suffered from pruritus while using oral contraceptives. The literature on benign recurrent intrahepatic cholestasis since 1959 describes at least 57 cases. A familial form of this condition proved to be fairly common. There seems to be a relation to the intrahepatic cholestasis sometimes seen during pregnancy and during oral contraceptive use. The data of the family study are suggestive for an interrelation of the three types of intrahepatic cholestasis, although a common denominator remains obscure.     

Chronic pancreatitis: diagnosis

Chronic pancreatitis is a chronic, inflammatory process leading to destruction of the exocrine tissue, filorosis, and in some patients a loss of endocrine function. Because chronic pancreatitis results in a permanent destruction of pancreatic tissue, exocrine and/or endocrine pancreatic insufficiency may follow. However, owing to the tremendous reserve of pancreatic function, insufficiency may be subclinical at least in the beginning of the disease. The diagnosis of chronic pancreatitis is not difficult; it is based on a typical medical history, specific imaging procedures, and pancreatic function testing. The main differential diagnosis is to separate chronic pancreatitis form pancreatic carcinoma. In the present summary, the different imaging procedures and pancreatic function tests are discussed.     

Faculty-student mentoring. A father's chronic sorrow: a daughter's perspective

Chronic sorrow often affects not only an individual who has a chronic illness or disability but the family members as well. This is the story of how chronic sorrow affected the life of a man diagnosed with prostate cancer and the family members who lived through it with him. It is told in the first person by his daughter not only as a tribute to her father, but also as a prospective learning experience for anyone involved with an individual moving through a chronic or terminal illness or disability. It integrates theory, research, and personal experience in an effort to understand this common human response to a chronic or terminal illness.     

Endoscopic therapy of chronic pancreatitis

BACKGROUND/AIMS: Endoscopic therapy of chronic obstructive pancreatitis is an indubitable contribution to patients which brings immediate pain relief, enables an increased caloric food intake and improves the quality of patient's life. The authors describe their experience in a set of 42 subjects, in whom endoscopic papillotomy of the pancreatic duct was carried out after diagnosis of chronic obstructive pancreatitis. MATERIAL AND METHODS: Endoscopic papillotomy was performed in 42 patients. In 17 patients, papillotomy was followed by the drainage of the pancreatic duct. RESULTS: The treatment led to disappearance or significant decrease of the epigastric pain in 85.7% patients shortly after the treatment; in 47.1% of patients the painless period lasted for further 24 months after the therapy. Increase in body weight of about 2 kg occurred in 53% of treated subjects during the 2 years since the therapy. Complications in treatment, such as acute pancreatitis in 3 patients and bleeding in 2 were mastered conservatively. CONCLUSION: Endoscopic therapy of chronic pancreatitis is an alternative approach of managing the algic form of chronic obstructive pancreatitis. Changes in the area of Vater papilla, pathological content of pancreatic duct, structure or complications of chronic pancreatitis could be solved endoscopically with a minimum burden on patient. According to the experience of the authors, endoscopic papillotomy of pancreatic duct with contingent drainage led to the pain disappearence nearly in 50% of patients in the set of 42 subjects 24 months after the performance. This fact was followed with an increase in body weight in more than 50% of treated subjects. Minimum of complications put the endoscopic therapy among relatively safe and at the same time effective approach to chronic pancreatitis.     

Identification of a hereditary pancreatitis mutation in four West Virginia families

Hereditary pancreatitis (HP) is the second most common cause of chronic childhood pancreatitis in the United States. Mutations in the cationic trypsinogen gene on chromosome 7 are known to cause HP. We identified four families in West Virginia with symptoms consistent with HP. To determine whether members of these families had defects in the trypsinogen gene, we tested for linkage between the HP gene and simple tandem repeat markers on chromosome 7q and screened for a specific mutation in the cationic trypsinogen gene. Two-point linkage analysis indicated that the disease gene is closely linked to three 7q markers (D7S661, D7S2511, and D7S1805). Restriction fragment length polymorphism analysis showed that all clinically affected members and nonpenetrant carriers from the four families carried a G to A mutation in the third exon of the trypsinogen gene. These findings indicate that this mutation is the cause of HP in the families in our study. The observation that most individuals who carry the mutation have symptoms of HP is consistent with the high but incomplete penetrance of the trait. The presence of a single mutation and a common linked haplotype indicates that the defective allele arose in an ancestor common to all four families.     

Emergency postcoital contraception

Pancreatitis may be acute or chronic, mild or severe. Acute necrotizing pancreatitis remains the most serious form of acute pancreatitis and accounts for the majority of complications. Although there is an established nomenclature for pancreatitis and pancreatic fluid collections, such as pancreatic pseudocysts, it is not widely understood or recognized by gastroenterologists. Because the management options for the treatment of pancreatic fluid collections continues to evolve with an increased use of endoscopic therapy, gastroenterologists will be increasingly called on to treat patients with pancreatitis and its complications. This article addresses and summarizes pancreatic fluid collections and their management, with an emphasis on endoscopic drainage.     

Pancreatic cancer screening. Analysis of the problem and the role of radionuclide imaging

The clinical, surgical, and pathologic findings in a five year prospective study of 192 patients referred with a high probability of pancreatic cancer are reported. We have defined the requirements of any pancreatic imaging procedure as its ability to distinguish a normal pancreas from pancreatic cancer or chronic pancreatitis and the capability of detecting tumors less than 5 cm in diameter. There was a 47 percent incidence of pancreatic disease (27 percent pancreatic cancer and 20 percent chronic pancreatitis). Prospective radionuclide imaging as routinely performed was found to be of little clinical value in this patient population; it was neither specific nor sensitive to pancreatic cancer or chronic pancreatitis. Preliminary data with longitudinal multiplane emission tomography show an improved diagnostic accuracy and the ability to detect resectable tumors, but its efficacy needs to be prospectively compared with other screening tests on a carefully defined patient population.     

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.     

Autoimmune pancreatitis: CT and MR characteristics

OBJECTIVE: Our goal was to elucidate the CT and MR imaging characteristics in patients with autoimmune pancreatitis, which is a reversible chronic pancreatitis with an autoimmune cause. CONCLUSION: On CT and MR imaging, a capsulelike rim, which is thought to correspond to an inflammatory process involving peripancreatic tissues, appears to be a characteristic finding of autoimmune pancreatitis. Also, diffuse pancreatic enlargement along with hypointensity on T1-weighted MR images and delayed enhancement on dynamic CT and MR studies are other features of this disorder.     

Family dynamics in end-of-life treatment decisions

The decision to withhold or withdraw life-sustaining treatment is now regularly weighed in chronic or terminal illness. Families are usually supportive advocates and concerned surrogate decision makers for patients, although they can also counter the wishes of the patient and disagree with the treatment team. Understanding the range of factors--internal and external, confronting the individual members and the family as a whole--that can influence family responses helps in working with families at this critical juncture in an illness. Interventions to assist the family and treatment team are discussed.     

Mutations of the cystic fibrosis gene in patients with chronic pancreatitis

BACKGROUND: The pancreatic lesions of cystic fibrosis develop in utero and closely resemble those of chronic pancreatitis. Therefore, we hypothesized that mutations of the cystic fibrosis transmembrane conductance regulator (CFTR) gene may be more common than expected among patients with chronic pancreatitis. METHODS: We studied 134 consecutive patients with chronic pancreatitis (alcohol-related disease in 71, hyperparathyroidism in 2, hypertriglyceridemia in 1, and idiopathic disease in 60). We examined DNA for 22 mutations of the CFTR gene that together account for 95 percent of all mutations in patients with cystic fibrosis in the northwest of England. We also determined the length of the noncoding sequence of thymidines in intron 8, since the shorter the sequence, the lower the proportion of normal CFTR messenger RNA. RESULTS: The 94 male and 40 female patients ranged in age from 16 to 86 years. None had a mutation on both copies of the CFTR gene. Eighteen patients (13.4 percent), including 12 without alcoholism, had a CFTR mutation on one chromosome, as compared with a frequency of 5.3 percent among 600 local unrelated partners of persons with a family history of cystic fibrosis (P<0.001). A total of 10.4 percent of the patients had the 5T allele in intron 8 (14 of 134), which is twice the expected frequency (P=0.008). Four patients were heterozygous for both a CFTR mutation and the 5T allele. Patients with a CFTR mutation were younger than those with no mutations (P=0.03). None had the combination of sinopulmonary disease, high sweat electrolyte concentrations, and low nasal potential-difference values that are diagnostic of cystic fibrosis. CONCLUSIONS: Mutations of the CFTR gene and the 5T genotype are associated with chronic pancreatitis.     

First report of association of chronic pancreatitis, primary biliary cirrhosis, and systemic sclerosis

We report an original observation of chronic pancreatitis associated with primary biliary cirrhosis and systemic sclerosis. The diagnosis of each of these conditions was unequivocally confirmed. Pancreatic involvement in this case was asymptomatic. The association of chronic pancreatitis with primary biliary cirrhosis has been previously reported and pancreatitis has been associated with other autoimmune disorders. We hypothesize about the underlying pathogenic mechanisms of chronic pancreatitis in our case.     

Diagnostic features of chronic pancreatitis distal to benign and to malignant pancreatic duct obstruction

Differentiation between diffuse chronic pancreatitis and pancreatitis distal to a malignant or benign stenosis has important prognostic and therapeutic implications. We examined the retrograde pancreatograms of 64 patients with histologically confirmed diagnosis of diffuse chronic pancreatitis, chronic pancreatitis distal to a benign tumor and chronic pancreatitis distal to a malignant tumor. The nature of the stenosis was often difficult to determine from the shape of the pancreatic duct only. By using discriminant analysis it was possible to determine an allocation rule based on 8 criteria mainly derived from changes in the pancreatic ductuli. This allocation rule allowed the correct diagnosis to be made in 24 out of 26 patients with diffuse chronic pancreatitis (92%), 19 out of 20 patients with pancreatitis distal to a benign tumor (95%) and all 18 patients (100%) with pancreatitis distal to a malignancy.     

A survey of mental health consumers' and family members' involvement in advocacy

As the service delivery system is redesigned, the involvement of consumers and family members in mental health policy-making is essential. Advocacy is a way for them to have an impact on policy or decision-making. To determine the extent of their participation in advocacy efforts, consumers and family members were surveyed by other consumers and family members about their involvement in advocacy and mental healthcare reform. Although more family than consumers reported receiving mental healthcare reform information, both groups had difficulty understanding this information. Consumers were more likely to have received information from a mental health professional while family were more likely to have received information from an advocacy group. Lack of economic resources and communication problems were the most often cited barriers to advocacy for consumers. Strategies are suggested for how to increase involvement of consumers and family in advocacy efforts. The limitations of conducting a state-wide study with consumers and family as data collectors is discussed.     

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.     

Inferior vena caval thrombosis associated with acute pancreatitis: an unusual vascular complication--its presentation and management

Vascular thrombosis and systemic hypercoagulable states are known complications of acute pancreatitis. They are thought to be secondary to the release of proteolytic enzymes of the pancreas. Inferior vena caval thrombosis is an extremely rare complication of chronic pancreatitis and has, to the authors' knowledge, never been reported in acute pancreatitis. The clinical presentation and radiographic findings are reviewed to illustrate the disease spectrum. Early treatment with intravenous heparin appears to be an effective therapy. Familiarity with this complication will aid physicians in its early diagnosis. However, a high degree of suspicion for this complication is necessary to make a diagnosis.     

Parenteral versus enteral nutrition: morphological changes in human adult intestinal mucosa

In animal experiments total parenteral nutrition induces an atrophy of the small intestinal mucosa. In humans morphological data are few and controversial. Therefore, the aim of this study was to investigate the effect of parenteral nutrition on the intestinal mucosa of human adults. For this purpose samples of the proximal jejunum of a) patients with chronic pancreatitis receiving total parenteral nutrition as presurgical treatment, b) enterally nourished patients without (controls) and c) with chronic pancreatitis were compared using light and scanning electron microscopy. Statistical differences were assessed applying computer-assisted morphometry. The results demonstrated that the thickness of the jejunal mucosa decreased already in enterally nourished patients with chronic pancreatitis. However, after total parenteral nutrition the decrease (atrophy) was enhanced due to a strong reduction in villus height albeit the crypt length increased. In addition, scanning electron microscopy revealed distinctive changes in mucosal surface pattern, whereby finger-like villi were replaced by leaf-like villi and by long, winding bifurcating ridges. Cell shedding was absent. In conclusion, total parenteral nutrition in humans induces 1) an atrophy and 2) a remodelling of the intestinal mucosa (epithelium and lamina propria) with a decrease in the absorbing surface. These alterations involve both cell proliferation and cell shedding. The response of the mucosa to parenteral nutrition is immediate and the effect of the treatment in bringing about morphological alterations is more efficacious at the beginning than in the successive period. The basic disorder (chronic pancreatitis) of the patients nourished parenterally contributes to mucosal atrophy, but not to remodelling.     

Monitoring of gastric acidity following ductal decompression surgery for chronic pancreatitis

The accepted decompression methods of chronic pancreatitis are the longitudinal pancreaticogastrostomy and the conventional pancreaticojejunostomy. The aim of the present study was to estimate the effect of these types of drainage operations on gastric acidity and to evaluate the clinical results. Between Jan. 1992 to 1996 56 patients with chronic pancreatitis were selected into the investigation who were operated in our clinic. A 24 hour gastric monitoring was taken on every patient before and 6 weeks after the operation. Following a complete postoperative check up we found that both types of operations are effective for pain relief (71%). Retrospectively 83% of the patients had no digestive problems due to pancreatic enzyme substitution. According to our statistical evaluation of 24 hour gastric pH monitoring test no alteration was detected in gastric pH in both groups pre- and postoperatively. On the basis of pH measuring and evaluated data we consider that pancreaticogastrostomy is a good operation choice to relieve intractable pain in selected patients with chronic pancreatitis associated with duct dilatation.