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Hereditary pancreatitis, an autosomal dominant disease with approximately 80% penetrance, can be caused by both 'gain-of-function' missense and copy number mutations in the cationic trypsinogen gene (PRSS1). Here we demonstrate a heterozygous hybrid PRSS2 (encoding anionic trypsinogen)/PRSS1 gene in a French white family with hereditary pancreatitis, by means of quantitative fluorescent multiplex PCR and RT-PCR analyses. The hybrid gene, in which exons 1 and 2 are derived from PRSS2 and exons 3-5 from PRSS1, apparently resulted from a non-allelic homologous recombination (NAHR) event between the chromosome 7 homologs or sister chromatids during meiosis. Interestingly, this hybrid gene causes the disease through a combination of its inherent 'double gain-of-function' effect, acting simultaneously as a 'quantitative' copy number mutation and a 'qualitative' missense mutation (i.e. the known disease-causing p.N29I mutation). Our finding reveals a previously unknown mechanism causing human inherited disease, enriches the lexicon of human genetic variation and goes beyond the known interaction between copy number variations (CNVs) and single nucleotide substitutions in health and disease. Our finding should also stimulate more interest in analyzing both types of genetic variation whenever one tries to determine the contribution of a specific locus to a given disease phenotype.

Objectives: Endoscopy offers an alternative to surgery for the treatment of ductal complications in patients with chronic pancreatitis. The aim of this study was to evaluate the efficacy of endoscopic treatment on pain, cholestasis and pseudocysts in these patients., Patients and Methods: Thirty-nine patients (37 M, 2 F, mean age 44), were included in the study. All patients had at least one of the following criteria demonstrated by imaging tests: dilatation of the main pancreatic duct (MPD) with or without stricture (N = 13), bile duct stricture (N = 12), or pancreatic pseudocyst (N = 14) with pancreatic duct stricture (N = 11) or biliary stricture (N = 3). Pancreatic or biliary sphincterotomy, insertion of pancreatic or biliary stent, pseudocyst drainage with stent placement were performed according to ductal abnormalities. Patients were evaluated early and followed up during the stenting period, and after stent removal., Results: Patients underwent a median of 3.5 endoscopic procedures with an interval of 2.2 months between 2 stenting sessions. A pancreatic or biliary stent was inserted in 25 patients with ductal abnormalities and in 11 patients with pseudocysts. Endoscopic pseudocyst drainage was performed in 6 cases. The mean stenting time was 6 months (range: 3-21). Mean follow-up after stent removal was 9.7 (2-48) months. Complications of endoscopic treatment were encountered in 7% of patients with no deaths. Pain relief was achieved after the first endoscopic procedure and during the overall stenting period in all patients. Recurrence of pain was observed after stent removal in 5/11 patients, requiring surgery in 4. Cholestasis decreased and biochemical values normalized within one month after biliary stenting. Recurrence of cholestasis was observed early after stent removal in 4/9 patients who required complementary surgical treatment. No recurrence of pancreatic pseudocyst was observed after endoscopic drainage and stent removal during the follow-up period., Conclusions: Endoscopic treatment of pain from pancreatic pseudocysts or ductal strictures is effective in the short-term and in the period of ductal stenting. However, the optimal duration of the latter remains to be determined.

Pancreas divisum, the most frequent congenital malformation of the pancreas, results from the absence of embryologic fusion of the dorsal and ventral pancreatic ducts which keep an autonomy of drainage. The dorsal pancreatic duct is dominant and drains the major part of the pancreatic fluid through a non adapted accessory papilla. The high prevalence of pancreas divisum in patients presenting recurrent acute pancreatitis, the presence of obstructive pancreatitis electively located on the dorsal pancreatic duct and the results of the treatments targeted on the accessory papilla are the arguments pleading for the pathogenic character of the pancreas divisum. Currently, the diagnosis of pancreas divisum is based on magnetic resonance imaging. For symptomatic patients (after exclusion of patients with intestinal functional disorders), results of endoscopic sphincterotomy or surgical sphincteroplasty are favourable in 75% of patients with recurrent acute pancreatitis. They are worse in patients with chronic pain. Surgical sphincteroplasty must be discussed in the same manner as the endoscopic treatment for sometimes avoiding multiplication of the procedures.

Numerous infectious agents may induce acute pancreatitis. We report 6 cases of Salmonella-associated acute pancreatitis. Pathogenesis of this type of pancreatitis is related to multiple factors that may coexist in the same patient. The typical clinical picture consists in epigastric pain, nausea, vomiting, diarrhoea and fever. Imaging techniques often disclose minimal changes such as moderate swelling of a part or of the totality of pancreas. As outcome is usually good, conservative treatment and antibiotics may be sufficient to ensure recovery.

The concentrations of cefepime in pancreatic pseudocyst fluid (n = 4), pancreatic tissue (n = 4) and pancreatic fistula fluid (n = 1), and simultaneous plasma concentrations, were measured after intravenous administration of a single 2 g dose to nine patients. Mean plasma concentration was 27.4 mg/L between 120 and 200 min after the end of infusion. Mean pancreatic cefepime concentration was 6.3 mg/L in pseudocyst and 10.7 mg/L in pancreatic tissue. Cefepime was detected by 30 min after the end of the perfusion in pancreatic fistulae fluid, and persisted at 8 h. We conclude that cefepime is a potentially useful antibiotic in prevention and treatment of pancreatic infection.

The pancreatic toxicity of oral 5-aminosalicylic acid (5ASA) derivatives used for the treatment of inflammatory bowel diseases remains controversial. A new case of mesalazine-induced acute pancreatitis (AP), with positive rechallenge, and an analysis of the previous published cases are presented. Twenty-nine patients (17 women, 12 men), aged 26.4 +/- 9.9 (12-43) years, were involved, receiving sulfasalazine (n = 11), mesalazine (n = 16), olsalazine (n = 1) or 5ASA without further informations (n = 1), for ulcerative colitis (n = 15), Crohn's disease (n = 13) or another indication (n = 1). The AP occurred in the first month of treatment in 71.4 per cent of the cases (n = 28). The clinical course was essentially benign in most of the cases. Recurrence of AP after rechallenge was observed in 17 of the 19 cases, even if the molecule, the dose or the form were modified. These results show that all 5ASA derivatives are potentially pancreatotoxic. An AP must be considered when an occurrence or increase of abdominal pain occurs during such therapy and warrants serum amylase assay and discontinuation of the drug.

Background/aims: The period of refeeding in patients with acute pancreatitis is critical because they may have pain relapse. A multicentre, multidimensional, prospective study was performed to assess the frequency and the risk factors of pain relapse in these patients., Methods: Patients were included if they had acute pancreatitis severe enough to stop oral feeding for more than 48 hours. Clinical, biochemical, radiological, and therapeutic data were prospectively recorded and analysed by unidimensional and multidimensional analysis. The moment to refeed patients was chosen by the clinician but the diet was the same in all centres., Results: A total of 116 patients were included with a Ranson's bioclinical score > or = 3 in 35% and a Balthazar's CT score > or = D in 42%. The cause of acute pancreatitis was biliary in 47% and alcohol misuse in 31%. During the oral refeeding period, 21% of the patients had pain relapse. This occurred on days 1 and 2 in 50% of patients. The duration of the painful period was longer in patients who relapsed than in others (p < 0.002). Pain relapse occurred in 39% of patients with a serum lipase concentration > 3x the upper limit of the normal range the day before refeeding and in 16% of other patients (p < 0.03). Patients with higher Balthazar's CT scores had pain relapse more often than the others (p < 0.002). None of the therapeutic procedures significantly modified the frequency of pain relapse. Using multidimensional analysis, Balathazar's CT score, period of pain, and serum lipase concentration the day before refeeding were independently associated with an increased risk of pain relapse. At a threshold of 0.5, a logistic score had a 37% sensitivity, 95% specificity, and 83% accuracy to predict pain relapse. Pain relapse nearly doubled total hospital stay and hospital stay after the first attempt at oral refeeding., Conclusion: Pain relapse occurred in one fifth of the patients with acute pancreatitis during oral refeeding and was more common in patients with necrotic pancreatitis and with longer periods of pain. The results of this study can be used to predict high risk patients and are a first step in the prevention of pain relapse.

Pancreaticopleural fistula is a rare complication of pancreatic diseases. It results from communication between a pancreatic duct and the pleural space, either directly, or through a pseudocyst. The treatment is medical or surgical. We report a case of pancreaticopleural fistula occurring in a man suffering from chronic pancreatitis, and treated by endoscopy.

Two cases of fibrotic stricture of the extrapancreatic common bile duct were observed 3 and 5.5 months after severe acute alcoholic pancreatitis. The diagnosis was made by endoscopic retrograde cholangiography in both cases. Although colonic or ureteric stenosis have been reported after acute pancreatitis, this is the first report of extrapancreatic biliary stricture occurring after acute pancreatitis. The strictures could have arisen by either an enzymatic or ischemic mechanism. Outcome was favorable after surgical hepaticojejunostomy.

The pancreaticoportal fistula is a very uncommon complication of pancreatic diseases, mostly occurring in the course of chronic pancreatitis. From 2 findings of pancreaticoportal fistula and a literature review, we emphasize in this study the frequency of subcutaneous fat necrosis during pancreaticoportal fistula, the pathogenic role of the pancreaticoportal fistula to induce a subcutaneous fat necrosis by means of a massive enzyme release in the systemic circulation, the protective role of portal thrombosis, and finally the diagnostic and therapeutic value of endoscopic retrograde cholangio-pancreatography in pancreaticoportal fistula.

During the 22nd week of her first pregnancy, a 28-year-old woman developed an attack of acute pancreatitis 10 months after pancreatoduodenectomy for chronic pancreatitis of alcoholic origin. She received total parenteral nutrition without complications for 83 days until the cesarean delivery of a child weighing 2,120 g. During that time, clinical, biological, and echographic signs of pancreatitis progressively disappeared. The favorable outcome for both mother and fetus suggests that prolonged TPN may be a useful measure in the management of severe digestive disease occurring during pregnancy.

We report the case of a 66 year-old man who developed acute necrotizing pancreatitis. The usual etiologies of acute pancreatitis were easily excluded. Endoscopic retrograde cholangiopancreatography demonstrated a 10 mm diameter filling defect in the distal common bile duct. After endoscopic sphincterotomy, a polypoid tumour which appeared to arise from the common bile duct was delivered through the wound. Diathermic resection of the tumor was performed. Microscopic examination disclosed papillary adenoma, without histologic signs of malignancy. Follow-up was favorable.