L. Rigo

Alcohol and Smoking as Risk Factors in Chronic Pancreatitis and Pancreatic Cancer

The aim of this study was to compare alcohol andsmoking as risk factors in the development of chronicpancreatitis and pancreatic cancer. We considered onlymale subjects: (1) 630 patients with chronic pancreatitis who developed 12 pancreatic and 47extrapancreatic cancers; (2) 69 patients withhistologically well documented pancreatic cancer and noclinical history of chronic pancreatitis; and (3) 700 random controls taken from the Verona pollinglist and submitted to a complete medical check-up.Chronic pancreatitis subjects drink more than controlsubjects and more than subjects with pancreatic cancer without chronic pancreatitis (P < 0.001).The percentage of smokers in the group with chronicpancreatitis is significantly higher than that in thecontrol group [odds ratio (OR) 17.3; 95% CI 12.6-23.8; P < 0.001] and in the group with pancreaticcarcinomas but with no history of chronic pancreatitis(OR 5.3; 95% CI 3.0-9.4; P < 0.001). In conclusion,our study shows that: (1) the risk of chronic pancreatitis correlates both with alcoholintake and with cigarette smoking with a trendindicating that the risk increases with increasedalcohol intake and cigarette consumption; (2) alcoholand smoking are statistically independent risk factors forchronic pancreatitis; and (3) the risk of pancreaticcancer correlates positively with cigarette smoking butnot with drinking.

Cigarette smoking : an independent risk factor in alcoholic pancreatitis

It is not known whether cigarette smoking plays a role as a risk factor in alcoholic pancreatitis. The aim of this study was to compare drinking and smoking habits in three groups of male subjects with an alcohol intake in excess of 40 g/day: (i) 67 patients with acute alcoholic pancreatitis, without other known potential causative agents; (ii) 396 patients with chronic alcoholic pancreatitis; and (iii) 265 control subjects randomly selected from the Verona polling lists and submitted to a complete medical checkup. The variables considered were age at onset of disease, years of drinking and smoking, daily alcohol intake in grams, number of cigarettes smoked daily, and body mass index (BMI). Cases differed from controls in daily grams of alcohol, number of cigarettes smoked and BMI (Mann-Whitney U test, p < 0.00001 for each comparison). Multivariate logistic regression analysis, comparing acute and chronic cases, respectively, versus controls, revealed an increased relative risk of pancreatitis in the two comparisons, associated in both cases with a higher alcohol intake (p < 0.00001) and cigarette smoking (p < 0.00001). No significant interaction between alcohol and smoking was noted, indicating that the two risks are independent. In conclusion, in males a higher number of cigarettes smoked daily seems to be a distinct risk factor in acute and chronic alcoholic pancreatitis.

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.

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.

Diabetes in chronic alcoholic pancreatitis : role of residual beta cell function and insulin resistance

Chronic alcoholic pancreatitis (CAP) is often complicated by the onset of diabetes mellitus. The aim of this study was to assess the residual beta cell function (evaluated by means of the glucagon test) and the mean disposal rate of insulin (with the insulin tolerance test) in 66 CAP patients with or without abnormalities of glucose metabolism and in 19 control subjects. On the basis of our data, we conclude that the glucose metabolism abnormalities in chronic pancreatitis occurs as a result not merely of impaired production of endogenous insulin, but also as result of a combination of the latter together with insulin resistance.

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.