M. Filippini

Effect of alcohol and smoking on pancreatic lithogenesis in the course of chronic pancreatitis.

The aim of the study was to establish whether correlations were discernible between calcification, smoking, and other variables—including alcohol intake—in chronic pancreatitis. A total of 637 patients with chronic pancreatitis diagnosed over the period of 1973—1989 were reviewed. Only patients who had had one or more instrumental tests (ultrasonography, endoscopic retrograde cholangiopancreatography, computed tomography, plain film of the abdomen) every 3 years were included in the study. Onset of calcification was taken as the end point of the follow-up. No statistically significant correlation was found between alcohol intake and calcification. As regards smoking habits, patients were divided into two groups: nonsmokers and medium-to-heavy smokers (210 cigarettedday). Of 637 patients, only 570 fulfilled our criteria. Three hundred seventy-six patients (66%) developed calcifications, whereas 64 (10%) already presented calcifications at the time of diagnosis. Smoking correlated with formation of calcifications (p < 0.004). The mean time to onset of calcification in smokers was 8 years as against 12 years in nonsmokers. The relative risk of calcification in smokers versus nonsmokers was 1.21 (95% confidence limits: 1.10-1.32). By the end of follow-up (17 years), 277 smokers (69%) with chronic pancreatitis had developed calcifications compared with only 93 nonsmokers (55%). The results show that, in this sample of chronic pancreatitis sufferers, smokers present a significantly increased risk of developing calcifications.

Long-term follow-up of patients with chronic pancreatitis in Italy.

BACKGROUND We investigated the epidemiologic, clinical, and radiologic aspects of a mixed medicosurgical series of chronic pancreatitis patients observed at the University of Verona Centre for the Study of Pancreatic Diseases over the period 1971-1995. METHODS Even though the pathogenesis of chronic pancreatitis has yet to be clarified and the classification is still debatable, the patients were subdivided in accordance with the Marseilles-Rome classification into those with alcoholic, obstructive, familial, and idiopathic forms of the disease. A total of 715 patients were analysed with a median follow-up period of 10 years (range, 1-25 years). RESULTS AND CONCLUSIONS At the end of follow-up the dropout rate amounted to 7.1% (51 patients), and 176 patients (24.6%) had died. Data are reported about the type of chronic pancreatitis, sex, and age distribution at the onset of the disease, drinking and smoking habits before onset and during follow-up, and incidence of calcifications, pain, diabetes, steatorrhoea, and pseudocysts. Surgical aspects, survival curves, and causes of death are also analysed, and the most frequent concomitant diseases in chronic pancreatitis sufferers are discussed.

Comparison of Ultrasound-Secretin Test and Sphincter of Oddi Manometry in Patients with Recurrent Acute Pancreatitis

Manometry is considered the gold standard forevaluating sphincter of Oddi dysfunction. It hasrecently been demonstrated that the ultrasound (US)secretin test proposed a few years ago as a noninvasive test for the study of sphincter of Oddidysfunction yields a substantial percentage ofpathological findings in patients with acute recurrentpancreatitis. The aim of this study was to compare theresults of the US secretin test with sphincter of Oddimanometry findings in a consecutive series of patientswith recurrent acute pancreatitis. Forty-seven patientsadmitted to our gastrointestinal unit suffering from recurrent acute pancreatitis underwentultrasonographic measurement of the main pancreatic ductat baseline and for 60 min after maximal stimulationwith secretin at 1 IU/kg. According to the US secretin test findings in 35 healthy control subjects,the test results were considered to indicate pathologywhen the duct was still dilated after 20 min. Withinthree to seven days the same patients underwent perendoscopic manometry. Thirty-six patients(17 men, 19 women; mean age 41 ± 15 years) had asuccessful US secretin test and sphincter of Oddimanometry. Eleven patients (30.6%) presented normalmanometric findings. Two of these had an abnormal USsecretin test. Twenty-five patients had abnormalmanometry findings, revealing stenosis in 19 (52.7%) (17with abnormal US secretin test) and dyskinesia in six (five with an abnormal US secretin test).Compared to manometry findings, the US secretin testsensitivity and specificity for sphincter of Oddidysfunction were 88% and 82%, respectively. Inconclusion, most patients with recurrent acute pancreatitishave sphincter of Oddi dysfunction documented by both atthe US secretin test and sphincter of Oddi manometry;results of the US secretin test are reliable compared to sphincter of Oddi manometry, andtherefore the US secretin test may offer a validalternative to the more expensive and invasivemanometric procedure for assessing sphincter of Oddidysfunction in patients with recurrent acutepancreatitis.

Effect of octreotide on sphincter of Oddi motility in patients with acute recurrent pancreatitis: a manometric study.

Sphincter of Oddi dysfunction has been reported as a cause of acute idiopathic recurrent pancreatitis (IRP). Octreotide, a long-acting somatostatin analogue, is an antisecretory drug used in the treatment and prevention of acute pancreatitis. Its action on sphincter of Oddi motility is controversial and no data are available for IRP patients. The aim of this study was to assess sphincter of Oddi motor response to acute administration of octreotide in patients with past attacks of acute pancreatitis without identification of any evident aetiological factor. Six patients (four male, two female; mean age ± SD, 38.8 ± 9 years) suffering from acute pancreatitis for at least 3 months before the examination were submitted to sphincter of Oddi manometry. After a basal recording lasting at least 2 min, octreotide, 0.05 mg i.v., was administered and the recording repeated. Intraduodenal pressure was taken as the zero reference and the basal sphincter of Oddi pressure and amplitude and frequency of phasic contractions were calculated before and after octreotide administration. No significant pre- vs post-octreotide differences were observed in basal pressure (41.9 ± 24 vs 47.5 ± 33 mm Hg, respectively) or in amplitude of phasic contractions (164.6 ± 33 vs 170.8 ± 18 mm Hg). With a latency of about 1 min, octreotide administration caused a high-frequency phasic activity in all cases (mean frequency, 5.5 ± 2.2 contractions/min before and 9.8 ± 2 after octreotide; P < 0.04). After the procedure acute pancreatitis (prolonged abdominal pain and serum amylase levels more than three-fold the normal values) developed in five patients. In conclusion, our data suggest that acute administration of octreotide may induce tachyoddia and thus a rise in sphincter of Oddi pressure, with possible impairment of biliary-pancreatic outflow.

Abnormal US response of main pancreatic duct after secretin stimulation in patients with acute pancreatitis of different etiology.

To assess changes in caliber of the main pancreatic duct, we performed abdominal ultrasonography after maximal stimulation with secretin (US-S test) in 14 patients with idiopathic recurrent acute pancreatitis, in six with recurrent acute pancreatitis secondary to pancreas divisum, in 14 recovered from a single attack of acute pancreatitis, and in 21 control subjects. In five patients, the test was repeated 10 days after endoscopic sphincterotomy. We repeated the test 48 h later in nine subjects to evaluate its reliability. We evaluated changes in lipase serum values in some of these subjects. In the acute pancreatitis patients, the main pancreatic duct diameter was significantly increased over baseline and control values throughout the observation period. In the patients undergoing sphincterotomy, the poststimulation diameter of the main duct was substantially reduced after the operation. The reliability of the test ranged from 77 to 91.5%. In the acute pancreatitis patients, serum enzymes after secretin stimulation showed a persistent increase over controls. These results suggest that pancreatic outlet obstruction, mainly at the sphincter of Oddi level, may be an important pathogenetic factor in the course of the disease and that, if this condition is present after an attack of acute pancreatitis, endoscopic sphincterotomy may be in order. The simplicity and satisfactory reproducibility of the US-S test suggest a strong case for its routine clinical use.

Intraluminal gastric pH in chronic pancreatitis.

The aim of this study was to assess the circadian variations of intragastric pH in 28 inpatients with chronic pancreatitis (mean (SD) age 46.8 (12.4) years) and in 14 controls (45.4 (9.8)). pH Metry was performed using a monocrystalline antimony electrode placed in the body of the stomach under fluoroscopic control and connected up to a recorder (MKII Digitrapper, Synectics). The evaluation parameters, expressed as median and interquartile range, were: total period, postprandial periods (P1 and P2), interdigestive, and nocturnal phases. Patients with chronic pancreatitis were subdivided into three groups on the basis of severity of exocrine pancreatic insufficiency (secretin-caerulein test: lipase output at 60-90 min)--that is, those with severe insufficiency (chronic pancreatitis-SI: 13 patients, lipase output < 10% normal values and pancreolauryl test < 20%), those with only mild insufficiency (chronic pancreatitis-MI: seven patients), and those with normal secretion (chronic pancreatitis-NF: eight patients). The chronic pancreatitis-SI patients present significantly greater gastric acidification in the postprandial periods compared with controls (P1: p < 0.001; P2: p < 0.01), and with chronic pancreatitis-MI plus chronic pancreatitis-NF subjects (P1: p < 0.01; P2: p < 0.05), taken together. In conclusion, gastric acidity, exocrine pancreatic insufficiency, and impaired digestion are closely related during the course of chronic pancreatitis.

Chronic obstructive pancreatitis in humans is a lithiasic disease.

In humans chronic obstructive pancreatitis (COP) is thought to be a disease devoid of ductal stones. The aim of this study was to verify the presence and frequency of calcifications in patients with COP and compare them with those found in patients with chronic cal-cifying/calcific pancreatitis (CCP). We conducted a retrospective ERCP investigation in 115 patients with documented chronic pancreatitis. Only 75 could be safely classified as COP or CCP. Fifty-three patients (M:F ratio, 5.6:l; mean age, 36.1 ± 12.2 years) had CCP, 46 of whom (86.8%) with calcifications. Twenty-two patients (M:F ratio, 3.4:l; mean age, 45.3 ± 16.3 years; p < 0.05 vs. CCP) presented COP at endoscopic retrograde cholangiopan-creatography. 8 (36.4%) with ductal calcifications (p < 0.0001 vs. CCP). COP was secondary to acute pancreatitis in nine cases, to odditis in 11 cases, and to malignant tumor and hypertrophy of Oddis sphincter, respectively, in the other two cases. The two patient groups showed no significant differences in drinking and smoking habits, number of painful relapses, disease duration, and incidence of diabetes, gallstones, and need for surgery. In conclusion, formation of ductal stones is by no means rare in COP and should be classified as a form of lithiasic pancreatitis. Early restoration of pancreatic outflow by removing the obstruction, or by shunt-type operations and abstinence from drinking and smoking, should resolve this type of disease.

Ultrasonography-secretin test pattern after acute administration of octreotide in healthy persons and in patients with recurrent acute pancreatitis.

The intravenous administration of octreotide stimulates sphincter of Oddi activity and impairs pancreatic flow into the duodenum. Postsecretin ultrasonography (US-S test) has revealed an increase in the caliber of the main pancreatic duct, which disappears in healthy persons approximately 10 minutes later as a result of the opening of the sphincter of Oddi and passage of stimulated fluids into the duodenum. We have assessed US-S test patterns after octreotide in healthy persons and in patients with recurrent acute pancreatitis. The study sample consisted of 16 participants: alcohol-abstinent, nonsmoking, healthy volunteers (four men, three women; mean age: 28 +/- 2.5 years) and nine patients with recurrent acute pancreatitis (six men, three women; mean age: 32.1 +/- 7.1 years). All participants underwent measurement of the main pancreatic duct at 1-min intervals for 60 min after secretin stimulation (1 IU/kg intravenous bolus). On a different day the same persons had repeated US-S tests 1 hour after administration of 0.1 mg octreotide intramuscularly. In both controls and patients with recurrent acute pancreatitis, octreotide administration induced an appreciable dilatation of the main pancreatic duct before secretin stimulation, and the caliber remained significantly increased throughout the duration of the test. These results suggest that a single administration of octreotide at the dose used (a) does not inhibit pancreatic secretion of basal and secretin-stimulated fluid within the first 60 min and (b) probably exerts an inhibitory effect on sphincter of Oddi relaxation. These findings warrant more intensive study given their therapeutic implications for acute pancreatic disease.

Autoimmunity and chronic pancreatitis.

1 Malbert C, Mathis C. Antropyloric modulation of transpyloric flow of liquids in pigs. Gastroenterology 1994; 107: 37-46. 2 Horowitz M, Dent J. The study of gastric mechanics and flow: a Mad Hatters tea party starting to make sense? Gastroenterology 1994; 107: 302-6. 3 Tougas G, Anvari M, Dent J, Somers S, Richards D, Stevenson G. Relation of pyloric motility to pyloric opening and closure in healthy subjects. Gut 1992; 33: 466-71. 4 Houghton L, Read N, Heddle R, Horowitz M, Collins PJ, Chatterton BE, et al. Relationship of the motor activity of the antrum, pylorus, and duodenum to gastric emptying of a solidliquid mixed meal. Gastroenterology 1988; 94: 1285-91. 5 Fone D, Horowitz M, Read N, Dent J, Maddox A. The effect of terminal ileal triglyceride infusion on gastroduodenal motility and the intragastric distribution of a solid meal. Gastroenterology 1990; 98: 568-75. 6 Fraser R, Horowitz M, Maddox A, Dent J. Dual effects of cisapride on gastric emptying and antropyloroduodenal motility. Am J Physiol 1993; 264: G195-201. 7 Fraser R, Horowitz M, Maddox A, Dent J. Postprandial motility and gastric emptying in gastroparesis the effect of cisapride. Gut 1994; 35: 172-8. 8 Sun W, Smout A, Malbert C, Edelbroet MAL, Jones K, Horowitz M, et al. Relationship between surface electrogastrography and antropyloric pressures. Am Jf Physiol (in press). 9 Heddle R, Dent J, Toouli J, Read N. Topography and measurement of pyloric pressure waves and tone in humans. Am Jf Physiol 1988; 255: G490-7. 10 Camilleri M, Malagelada J, Brown M, Becker G, Zinsmeister A. Relation between antral motility and gastric emptying of solids and liquids in humans. AmJ Physiol 1985; 249: G580-5. 11 Prather C, Camilleri M, Thomforde G, Forstrom L, Zinsmeister A. Gastric axial forces in experimentally-delayed and accelerated gastric emptying. Am J Physiol 1993; 264: G928-34. 12 Anvari M, Malbert C, Horowitz M, Jamieson G. Loxiglumide abolishes the effects of intraduodenal oleic acid on gastric motility and emptying in the pig. Neurogastroenterology Motility 1994; 6:181-8. 13 Camilleri M, Brown M, Malagelada J. Relationship between impaired gastric emptying and abnormal gastrointestinal motility. Gastroenterology 1986; 91: 94-9. 14 Camilleri M, Malagelada J. Abnormal intestinal motility in diabetics with the gastroparesis syndrome. EurJ Clin Invest 1984; 14: 420-7. 15 Azpiroz F, Malagelada J. Gastric tone measured by an electronic barostat in health and post surgical gastroparesis. Gastroenterology 1987; 92: 934-43. 16 Mearin F, Camilleri M, Malagelada J. Pyloric dysfunction in diabetics with recurrent nausea and vomiting. Gastroenterology 1986; 90: 1919-25.

Opinion from Italy

In agreement with Toouli [1], idiopathic recurrent acute pancreatitis (IRAP) can be defined as an infrequent clinical entity characterized by multiple episodes of usually clinically mild pancreatitis in the absence of the aetiological factors most commonly associated with acute pancreatitis such as cholelithiasis, alcohol abuse, pancreas divisum, hypercalcaemia, dyslipidaemia and viral infections. A number of investigators [2, 3] have postulated that a dysfunction at the sphincter of Oddi (SO) level may play a major role in the pathogenesis of this type of disease. The most suitable technique for verifying the presence or otherwise of a stenotic or dyskinetic sphincter of Oddi dysfunction (SOD) is mano-metry, usually performed by means of cannulation of the SO with a low-pressure perfusion catheter with three pressure gauges arranged axially at angles of 120° [4]. The examination, however, though very reliable, is rarely available as a routine procedure and requires special, expensive equipment and expert personnel.