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Background/Aims:Acute pancreatitis (AP) is characterized by premature zymogen activation, systemic inflammatory response resulting in inflammatory infiltrates, sustained intracellular calcium, neurogenic inflammation and pain. The inhibitory neurotransmitter and cytoprotective amino acid glycine exerts a direct inhibitory effect on inflammatory cells, inhibits calcium influx and neuronal activation and therefore represents a putative therapeutic agent in AP. Methods:To explore the impact of glycine, mild AP was induced in rats by supramaximal cerulein stimulation (10 µg/ kg BW/h) and severe AP by retrograde injection of sodium taurocholate solution (3%) into the common biliopancreatic duct. 100/300 mmol glycine was administered intravenously before induction of AP. To elucidate the effect of glycine on AP, we determined pathomorphology, pancreatic cytokines as well as proteases, serum lipase and amylase, pancreatic and lung MPO activity and pain sensation. Results:Glycine administration resulted in a noticeable improvement of pathomorphological alterations in AP, such as a reduction of necrosis, inflammatory infiltrates and cytoplasmic vacuoles in cerulein pancreatitis. In taurocholate pancreatitis, glycine additionally diminished pancreatic cytokines and MPO activity, as well as serum lipase and amylase levels. Conclusions:Glycine reduced the severity of mild and much more of severe AP by attenuating the intrapancreatic and systemic inflammatory response. Therefore, glycine seems to be a promising tool for prophylactic treatment of AP.

Background & Aims: Hereditary pancreatitis is an autosomal dominant disease that is mostly caused by cationic trypsinogen (PRSS1) gene mutations. The aim was to determine phenotype-genotype correlations of families in Europe. Methods: Analysis of data obtained by the European Registry of Hereditary Pancreatitis and Pancreatic Cancer was undertaken using multilevel proportional hazards modelling. Results: There were 112 families in 14 countries (418 affected individuals): 58 (52%) families carried the R122H, 24 (21%) the N29I, and 5 (4%) the A16V mutation, 2 had rare mutations, and 21 (19%) had no PRSS1 mutation. The median (95% confidence interval [CI]) time to first symptoms for R122H was 10 (8, 12) years of age, 14 (11, 18) years for N29I, and 14.5 (10, 21) years for mutation negative patients (P = 0.032). The cumulative risk (95% CI) at 50 years of age for exocrine failure was 37.2% (28.5%, 45.8%), 47.6% (37.1%, 58.1%) for endocrine failure, and 17.5% (12.2%, 22.7%) for pancreatic resection for pain. Time to resection was significantly reduced for females (P < 0.001) and those with the N29I mutation (P = 0.014). The cumulative risk (95% CI) of pancreatic cancer was 44.0% (8.0%, 80.0%) at 70 years from symptom onset with a standardized incidence ratio of 67% (50%, 82%). Conclusions: Symptoms in hereditary pancreatitis start in younger patients and endpoints take longer to be reached compared with other forms of chronic pancreatitis but the cumulative levels of exocrine and endocrine failure are much higher. There is an increasingly high risk of pancreatic cancer after the age of 50 years unrelated to the genotype.

Background: The double duct sign, a simultaneous stenosis of the common bile duct and the pancreatic duct by endoscopic retrograde cholangiopancreatography (ERCP), has been reported to predict the presence of pancreatic cancer with a high degree of certainty. Methods: To test the specificity of the double duct sign for pancreatic cancer in patients with malignant and benign pancreatic lesions, we have reviewed all ERCP films obtained during a 24-month period (n = 1209) and corresponding clinical follow-up data obtained during a period of 4 years. Results: Forty-three patients were identified as having a double duct stenosis on ERCP, 15% of whom did not have pancreatic carcinoma. In 4 patients chronic pancreatitis was confirmed by serial histologic sections of the surgical specimen. Data on the lengths of the stenotic segment in either the pancreatic duct or the bile duct did not contribute to a better discrimination between benign and malignant disease. Conclusion: The specificity of the double duct sign in predicting the presence of pancreatic cancer appears to be lower than previously reported. Better discrimination between malignant and benign disease of the pancreas will be difficult to achieve with existing imaging techniques. (Gastrointest Endosc 2000;52:74-7.)

A case of a 24-year-old male with fatal cerebro-renal oxalosis assumed to be due to infusions of the sugar surrogate xylitol after appendectomy is reported. The diagnosis was established only after intensive histological investigations following the autopsy. The clinical picture was characterized by an acute seizure, coma and renal failure 2 days after the first xylitol infusion. Death occurred due to cerebral dysregulation as a very rare complication after parenteral administration of xylitol. Subendothelial double refractive calcium oxalate crystals were found in the walls of cerebral blood vessels, in particular in the stem ganglion regions and in the cortical renal tubules. The most common type of primary oxalosis was excluded by sequencing analysis. The young age, the minor surgical intervention and the otherwise unremarkable history are special features of this case. Since the genetic background of xylitol intolerance is still unclear, it is suggested that it should be banned as a sugar surrogate in clinical practice.

GASTROENTEROLOGY 2000;118:771

GASTROENTEROLOGY 2000;118:379