P. Bovo

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.

Incidence of cancer in the course of chronic pancreatitis

Objective:Chronic pancreatitis patients appear to present an increased incidence of pancreatic cancer. The aim of the study was to compare the incidence of cancer, whether pancreatic or extrapancreatic, in our chronic pancreatitis cases with that in the population of our region.Methods:We analyzed 715 cases of chronic pancreatitis with a median follow-up of 10 yr (7287 person-years); during this observation period they developed 61 neoplasms, 14 of which were pancreatic cancers. The cancer incidence rates were compared, after correction for age and gender, with those of a tumour registry.Results:We documented a significant increase in incidence of both extrapancreatic (Standardized Incidence Ratio [SIR], 1.5; 95% confidence interval [CI], 1.1–2.0; p <0.003) and pancreatic cancer (SIR, 18.5; 95% CI, 10–30; p < 0.0001) in chronic pancreatitis patients. Even when excluding from the analysis the four cases of pancreatic cancer that occurred within 4 yr of clinical onset of chronic pancreatitis, the SIR is 13.3 (95% CI, 6.4–24.5; p < 0.0001). If we exclude these early-onset cancers, there would appear to be no increased risk of pancreatic cancer in nonsmokers, whereas in smokers this risk increases 15.6-fold.Conclusions:The risks of pancreatic and nonpancreatic cancers are increased in the course of chronic pancreatitis, the former being significantly higher than the latter. The very high incidence of pancreatic cancer in smokers probably suggests that, in addition to cigarette smoking, some other factor linked to chronic inflammation of the pancreas may be responsible for the increased risk.

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.

Exocrine Pancreatic Cancer, Cigarette Smoking, and Diabetes Mellitus: A Case-control Study in Northern Italy

The role of cigarette smoking and diabetes mellitus as risk factors for exocrine pancreatic cancer (PC) was investigated in a hospital based case-control study. Current smokers were at increased risk for PC (OR = 2.36, 95% CI 1.53–3.63): the magnitude of the risk was related to the lifetime amount of smoking (&khgr;2trend = 17.00; P < 0.0001). Among former smokers, after 15 years from ceasing smoking, the risk for PC dropped to the level of a lifetime non-smoker, whichever the lifetime smoking amount. Diabetes was associated with a 2.89-fold increased risk for PC (95% CI 1.71–4.86): the risk was 4.76 (95% CI 1.99–11.53) for diabetes diagnosed up to 2 years before the diagnosis of PC and dropped to 2.07 (95% CI 1.02–4.20) for diabetes diagnosed more than 5 years before PC. The risk for PC was estimated according to the treatment used to control diabetes: it was 6.49 (95% CI 2.28–18.48) for insulin treated diabetes and 2.12 (95% CI 1.16–3.87) for diabetes treated with oral hypoglycemic drugs. The risk of PC for diabetes treated for more than 5 years before the diagnosis of PC was 6.21 (95% CI 1.61–23.96) for patients treated with insulin and 1.21 (95% CI 0.50–2.92) for those treated with oral hypoglycemic drugs: the type of treatment needed to control the disease may discriminate between the diabetes that represents a consequence of cancer from the diabetes that could represent an etiological co-factor. More studies are needed to clarify whether long-lasting insulin-treated diabetes is an etiological co-factor in PC.

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.

Long-Term Outcome of Acute Pancreatitis: A Prospective Study with 118 Patients

118 patients who had recovered from acute pancreatitis underwent endoscopic retrograde pancreatography (ERCP) during a long-term follow-up (mean 4.4 years, range 1-17) to investigate the frequency and features of residual ductal lesions. Oedematous and necrohaemorrhagic pancreatitis occurred in 35 and in 83 patients, respectively. The aetiology was biliary (39 patients), alcoholic (32), biliary-alcoholic (18) and miscellaneous (29). After oedematous pancreatitis, ERCP was normal in 31, showed obstructive pancreatitis in 2 and a slight localized and smooth stricture of the main duct in 2 patients. After necrotizing pancreatitis, 29 patients showed ductal changes without features of chronic pancreatitis, 7 obstructive, 3 chronic calcifying pancreatitis and 44 normal pictures. In 17 patients submitted to two or three ERCPs during a mean 10-year follow-up, the ductal appearance was unchanged in 12, worsened in 3, and improved in 2 patients. The aetiology of pancreatitis and frequency of recurrences was similar in patients with or without scarring lesions. We conclude that residual ductal lesions are common after acute necrotizing pancreatitis.

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.

Pancreatic function in chronic inflammatory bowel disease.

SummaryThis study was prospectively carried out to evaluate the frequency and clinical significance of pancreatic impairment in the course of chronic inflammatory bowel disease (CIBD). Twenty-seven patients affected by ulcerative colitis or Crohns disease were submitted to a secretin-cerulein test, oral glucose test (OGT) and to indirect immunofluorescence (IFL) for detection of autoantibodies against exocrine and endocrine tissue. A bicarbonate plus enzyme or only an enzyme insufficiency was found in 11/27 patients, whereas isolated lipase decrease was observed in 18 subjects. In the results of the OGT and the indirect IFL test there was no difference between patients and controls. These data demonstrate that pancreatic impairment is a far more frequent occurrence than generally recognized in clinical practice. The decrease of lipase secretion could worsen the consequences of malabsorption in Crohns disease of the small intestine. Therefore we think that a pancreatic assessment is advisable, at least in Crohns disease patients with steatorrhea.

Elevated serum levels of antibodies to carbonic anhydrase I and II in patients with chronic pancreatitis.

An immune-mediated reaction to pancreatic structures has been postulated for the pathogenesis of chronic pancreatitis (CP). Several reports demonstrate the presence of antibodies to the pancreatic ductal epithelium in some patients suffering from CP. Serum antibodies to carbonic anhydrase I (anti-CA I) and II (anti-CA II) are present in patients affected by idiopathic CP. The aim of this study was to evaluate the presence of anti-CA I and anti-CA II in a series of patients with CP. We studied 78 consecutive CP patients (62 male, 16 female; mean age 48.6 ± 10.2 years) referred to the Verona University Center for the Study of the Pancreas. As a control group, we studied 26 healthy subjects recruited from among the medical and nursing staff of the center. Serum anti-CA I and anti-CA II levels were quantified by enzyme-linked immunosorbent assay using a standard method with minor modifications. The mean absorbance of antibodies was higher in CP patients than in control subjects (anti-CA I: 0.064 ± 0.042 vs. 0.047 ± 0.015, p = 0.051; and anti-CA II: 0.038 ± 0.02 vs. 0.029 ± 0.014, p = 0.033). Positive results were arbitrarily defined as absorbance values >0.067 for anti-CA I and 0.047 for anti-CA II. We found anti-CA I and anti-CA II positivity in 21 of 78 (27%) and 20 of 78 (26%) of CP patients, respectively, and in only two of 26 control subjects (7.7%) (p = 0.032 and 0.039). Twenty-two of 26 subjects in the control group (84.6%) and 48 of 78 patients (61.5%) in the CP group tested negative for both antibodies (p = 0.03). None of the control subjects and 12 of 78 (16.6%) of the CP patients tested positive for both anti-CA I and anti-CA II. We observed a significant correlation between anti-CA I and anti-CA II serum levels in control subjects (R = 0.423;p = 0.016) and in CP patients (R = 0.584;p < 0.0001). No correlation was found between serum antibody levels and any of the following variables: length of disease, alcohol consumption, smoking habits, pancreatic surgery, pancreatic calcifications, diabetes, and steatorrhea. Serum levels of anti-CA I and anti-CA II are elevated in some patients suffering from CP.