Peter Layer

THE DIFFERENT COURSES OF EARLY- AND LATE-ONSET IDIOPATHIC AND ALCOHOLIC CHRONIC PANCREATITIS

BACKGROUND/AIMSnCompared with alcoholic pancreatitis, little is known about the natural history of idiopathic pancreatitis. Two hundred forty-nine patients with alcoholic pancreatitis and 66 patients with idiopathic chronic pancreatitis seen at our institution between 1976 and 1982 were investigated.nnnMETHODSnRecords were analyzed retrospectively from the onset of symptomatic disease, and patients were followed up prospectively until 1985. Patients with early-onset (n = 25) and late-onset (n = 41) idiopathic chronic pancreatitis had a median age at onset of symptoms of 19 and 56 years, respectively.nnnRESULTSnThe gender distribution was nearly equal in idiopathic chronic pancreatitis, but 72% of patients with alcoholic pancreatitis were men (P = 0.001 vs. idiopathic). In early-onset idiopathic pancreatitis, calcification and exocrine and endocrine insufficiency developed more slowly than in late-onset idiopathic and alcoholic pancreatitis (P = 0.03). However, in early idiopathic chronic pancreatitis, pain frequently occurred initially (P = 0.003 vs. late and alcoholic) and was more severe (P = 0.04 vs. late and alcoholic). In late-onset idiopathic pancreatitis, pain was absent in nearly 50% of patients.nnnCONCLUSIONSnThere are two distinct forms of idiopathic chronic pancreatitis. Patients with early-onset pancreatitis have initially and thereafter a long course of severe pain but slowly develop morphological and functional pancreatic damage, whereas patients with late-onset pancreatitis have a mild and often a painless course. Both forms differ from alcoholic pancreatitis in their equal gender distribution and a much slower rate of calcification.

Effects of decreasing intraluminal amylase activity on starch digestion and postprandial gastrointestinal function in humans.

We used an amylase inhibitor preparation that markedly improves postprandial carbohydrate tolerance in humans to investigate the effects of decreased intraluminal amylase activity on digestion of starch and postprandial gastrointestinal and hormonal responses. Four fasting volunteers were intubated with an oroileal tube to obtain duodenal, jejunal, and terminal ileal samples. After intubation, subjects ingested 50 g of rice starch given with placebo; on the second day, starch was given with the amylase inhibitor. Compared with placebo, the amylase inhibitor significantly (p less than 0.05) reduced duodenal, jejunal, and ileal intraluminal amylase activity by more than 95% for 1-2 h; increased postprandial delivery of total carbohydrate (glucose polymers in particular) to the distal small bowel; increased breath hydrogen concentrations; decreased intestinal water absorption and increased distal intestinal volume delivery to the distal bowel; shortened duodenoileal transit time but doubled postprandial gastric emptying time; reduced the early postprandial plasma glucose rise by 85% and eliminated the late postprandial glucose fall to below fasting levels; and abolished postprandial plasma concentrations of insulin, C-peptide, and gastric inhibitory polypeptide. Postprandial trypsin output was not influenced. We conclude that more than 95% inhibition of amylase reduces dietary starch digestion within the small intestine and uptake of dietary starch from the small intestine, markedly decreases postprandial release of insulin and gastric inhibitory polypeptide, and may alter postprandial upper gastrointestinal motor function.

Partially purified white bean amylase inhibitor reduces starch digestion in vitro and inactivates intraduodenal amylase in humans

Whether commercial, bean-derived alpha-amylase inhibitor preparations failed to decrease starch digestion in humans because of insufficient antiamylase activity, destruction by gastrointestinal secretions, or decreased activity in the presence of starch is unknown. We used a simple partial purification procedure to markedly concentrate the inhibitor (sixfold to eightfold by total protein content, and 30-40-fold by dry weight). Compared with a commercial preparation and crude bean extract, this partially purified inhibitor inactivated intraduodenal, intraileal, and salivary amylase in vitro faster and more completely (p less than 0.001); its specific activity was not affected by exposure to gastric juice and was only minimally reduced by duodenal juice. Whereas the rate of amylase inhibition by inhibitor was markedly slowed in the presence of nondietary liquid starch, dietary solid starch had only a minimal effect. Consequently, the partially purified inhibitor had no effect on liquid starch digestion, but decreased in vitro digestion of dietary starch in a dose-dependent manner (p less than 0.001). Perfusion of the partially purified inhibitor (2.0, 3.5, or 5.0 mg/ml at 5 ml/min) into the duodenum of humans rapidly inhibited greater than 94%, greater than 99%, or greater than 99.9% of intraluminal amylase activity. We conclude that commercial amylase inhibitors failed to decrease starch digestion in vivo mainly because they have insufficient antiamylase activity. However, a partially purified inhibitor with increased specific activity is stable in human gastrointestinal secretions, slows dietary starch digestion in vitro, rapidly inactivates amylase in the human intestinal lumen, and, at acceptable oral doses, may decrease intraluminal digestion of starch in humans. Such an inhibitor therefore deserves study.

Drug-associated pancreatitis : Facts and fiction

In the past, numerous reports on drugs probably causing acute pancreatitis have been published. However, most of these case reports were anecdotal with a lack of obvious evidence and did not present a comprehensive summary. Although drug-associated pancreatitis is rare. it is gaining increasing importance with the introduction of several potent new agents, i.e., anti-acquired immunodeficiency syndrome drugs. The following comprehensive review scrutinizes the evidence present in the world literature on drugs associated with acute or chronic puncreatitis and, based on this, categorizes in a definite, probable, or possible causality. In addition, explanations for the pathophysiological mechanisms are discussed.

Feedback Regulation of Human Pancreatic Secretion: Effects of Protease Inhibition on Duodenal Delivery and Small Intestinal Transit of Pancreatic Enzymes

To determine the effects of luminal protease inhibition on duodenal delivery and the intraluminal fate of pancreatic enzymes, six healthy subjects were intubated with an oro-ileal multilumen tube assembly. By using nonabsorbable markers, cumulative trypsin, chymotrypsin, lipase, and amylase activities were measured as delivered to duodenum, midjejunum, and distal ileum, with or without simultaneous duodenal perfusion of the protease inhibitor camostat at graded doses. Compared with saline, camostat (a) inhibited trypsin activity in the entire small intestinal lumen by up to 99%, and significantly reduced chymotrypsin activity by up to 89%; (b) significantly increased duodenal deliveries of lipase activity, amylase activity and volume; (c) did not influence plasma cholecystokinin concentrations; and (d) significantly increased jejunal and ileal deliveries of lipase but not amylase activity. Small intestinal transit and motility were not affected by camostat. In additional in vitro studies, camostat significantly reduced the spontaneous decline in lipase activity in fresh human duodenal juice incubated at 37 degrees C. These findings demonstrate that duodenal deliveries of lipase and amylase activities increase when intraluminal protease activity is decreased; they suggest that this increase is not caused by slower proteolytic destruction of enzyme protein but by stimulation of pancreatic secretion. Thus, luminal protease-mediated feedback regulation of pancreatic secretion may be operative in humans. Because plasma cholecystokinin concentrations were not affected, these effects may in part be independent of cholecystokinin. The data further suggest that proteolytic digestion plays a major role in the rapid loss of luminal lipase activity on small intestinal transit.

The Effect of Small Amounts of Alcohol on the Clinical Course of Chronic Pancreatitis

OBJECTIVEnTo investigate the hypothesis that an increasing intake of alcohol accelerates the course of chronic pancreatitis.nnnPATIENTS AND METHODSnIn this retrospective record analysis and subsequent prospective follow-up of 372 patients with chronic pancreatitis, we separately compared the clinical course of chronic pancreatitis among the following patients: those with early-onset idiopathic chronic pancreatitis and no alcohol intake (group A [n=25]) and those with late-onset idiopathic chronic pancreatitis and no alcohol intake (group B [n=41]), low alcohol intake (< 50 g/d) (group C [n=57]), and high alcohol intake (> or = 50 g/d) (group D [n=249]). From medical records, physical examinations, questionnaires, death certificates, or autopsy reports, we obtained information on sex, age, signs and symptoms (pain severity, calcification, endocrine and exocrine insufficiency), complications, surgery, and survival.nnnRESULTSnGroup D had the highest percentage of men (72%). At the onset of chronic pancreatitis, patients in group A were significantly younger than those in groups B, C, and D (P<.05), and severity of pain was significantly greater in patients in group A than in groups B, C, and D (P<.05). The percentage of patients who eventually developed endocrine or exocrine insufficiency was similar in all groups. Among patients in groups B, C, and D, an increasing intake of alcohol from zero to less than 50 g/d to more than 50 g/d was associated with earlier inception of disease (P<.001). Pain prevalence at onset was less in group B patients than in patients in groups C and D (P<.05). Intake of a large amount of alcohol (group D) shortened time to calcification and survival (P<.05). In addition, patients in group D had more complications (fistulas, pseudocysts, abscesses, and biliary obstruction) (P<.05) than those in groups A and B. More patients in group A underwent pancreatic surgery compared with patients in groups B and C.nnnCONCLUSIONSnAmong patients with onset of chronic pancreatitis after age 35 years, alcohol intake, even less than 50 g/d, induced earlier disease characterized by more frequent severe pain, calcification, and complications. Intake of large amounts of alcohol (> or = 50 g/d) reduced time to calcification and death.

Modulation of human periodic interdigestive gastrointestinal motor and pancreatic function by the ileum.

Following ingestion of a meal, unabsorbed nutrients may reach the distal intestine partly after the termination of the prandial period, i.e., in the presence of interdigestive motor and secretory patterns. To determine if interdigestive motility and pancreatic enzyme secretion are modulated by the delivery of nutrient into the ileal lumen, six fasting volunteers were intubated with an oroileal multilumen tube system that permitted multiple small intestinal manometry, gastric and duodenal aspiration, and perfusions of marker and test solutions. Ileal perfusions of nutrient or saline solutions were started during phase I of the interdigestive motility cycle. Ileal perfusion with carbohydrate or lipids increased the duration of motor quiescence and decreased the length of the interdigestive cycle, mainly by decreasing the proportion of phase II activity compared with ileal saline (p <0.01). Pancreatic outputs of amylase, trypsin, and chymotrypsin prior to ileal perfusions were low because, due to the protocol, perfusions were started during phase I. With ileal saline, enzyme outputs increased (p <0.05) in association with the occurrence of phase I1 motility, as expected. By contrast, ileal carbohydrate and triglyceride perfusion prevented the phase 11-associated increase in enzyme outputs (p <0.05). The data suggest that the presence of nutrients within the ileal lumen may modulate interdigestive motor and pancreatic functions.

Effect of a Purified Amylase Inhibitor on Carbohydrate Tolerance in Normal Subjects and Patients With Diabetes Mellitus

Slowing starch digestion by inhibiting amylase activity in the intestinal lumen should improve postprandial carbohydrate tolerance in patients with diabetes mellitus. Crude bean-derived amylase inhibitor (starch blocker) that contains only minimal antiamylase activity, however, does not modify carbohydrate assimilation. To test the validity of the starch blockade concept, we assessed the effect of a partially purified bean-derived amylase inhibitor with increased antiamylase activity on carbohydrate tolerance in normal subjects and in patients with non-insulin-dependent diabetes mellitus. In comparison with a placebo, ingestion of this inhibitor with 50 g of starch substantially reduced postprandial increases in plasma concentrations of glucose and insulin in both normal subjects and those with diabetes. We conclude that a purified amylase inhibitor is effective and potentially beneficial in the treatment of diabetes mellitus.

Acute Postprandial Gastrointestinal and Metabolic Effects of Wheat Amylase Inhibitor (WAI) in Normal, Obese, and Diabetic Humans

Amylase inhibition has gastrointestinal and metabolic effects that may aid in the treatment of diabetes and obesity. We tested whether 4 g of a commercially available wheat amylase inhibitor (WAI) affected postprandial carbohydrate (CHO) absorption and plasma glucose or hormones. Twelve persons (four lean and four obese nondiabetics and four obese type II diabetics) were studied on 2 separate days. After eating a weight maintenance diet (55% CHO, 20% protein, and 25% fat, as percentage of calories) for 3 days, subjects ate a breakfast containing 650 kcal, the same proportion of nutrients as calories, and in random order, either WAI or no WAI. Breath H2 and plasma glucose and hormones were measured every 15 and 30 min, respectively, for 7 h. WAI decreased the A peak postprandial plasma glucose concentrations in 10 of 12 subjects (p <0.05) and increased the breath H2 levels in 11 (p = 0.02); the increases in breath H, were small, generally <20 ppm. No subject experienced a change in stools, diarrhea, or bloating. In response to WAI, gastric inhibitory peptide decreased (p <0.05), peptide YY increased (p <0.05), and there was a trend toward increased human pancreatic polypeptide (p = 0.07). Although WAI delays CHO absorption and reduces peak postprandial plasma glucose concentrations, overall CHO malabsorption is minimal (as reflected by breath hydrogen and hormones) and without symptoms. It, therefore, may be useful in treating type II diabetes mellitus.

Indications for Debridement of Necrotizing Pancreatitis

Editor-in-Chic.f s 1ntrodirc.tion In 1994, during the annual meeting of the Pancreas Editorial Board and t he American Pancreatic Association Governing Board, this new section in the journal was suggested and formally developed. The purpose of this section will be to address clinical controversies in the diagnosis and management of pancreatic diseases, and from time to time surveys will be conducted by the Committee on Controversies in Clinical Pancreatology and journal to identify clinical controversies in pancreatology of special interest to our readers. Dr. William Steinberg developed this section and has been appointed Chair, with members of the Committee listed above. Thus, we inaugurate this new section in Pmncrrus, which will become a regular feature of our journal.