Lucio Gullo

Acute pancreatitis in five European countries: etiology and mortality.

Introduction In recent years, many advances have been made in the diagnosis and treatment of acute pancreatitis that have lead to a significant reduction in both morbidity and mortality; however, knowledge of the etiology and of the relation between etiology and mortality is far from complete. Aim To obtain a more comprehensive view of the etiology and mortality of acute pancreatitis in Europe than has been given by previous single-center studies. Methodology The study comprised 1,068 patients in five European countries who were admitted to hospitals for acute pancreatitis from January 1990 to December 1994. Data for each patient were collected on a standardized form. Results Of the 1,068 patients (692 men, 376 women; mean age, 52.8 years; range, 10–95 years), 589 had edematous pancreatitis, and 479 the necrotic form. Cholelithiasis (37.1%) and alcohol (41.0%) were the most frequent etiologic factors. In Germany, cholelithiasis and alcohol occurred with similar frequency (34.9 and 37.9%, respectively); in Hungary, alcohol predominates over cholelithiasis (60.7 vs. 24.0%); in France, a small predominance of alcohol was seen (38.5 vs. 24.6%); and in Greece and Italy, there was a clear predominance of cholelithiasis over alcohol (71.4 vs. 6.0% and 60.3 vs. 13.2%, respectively). The differences in the frequency of cholelithiasis and alcohol between Greece and Italy and the other countries were statistically significant (p < 0.01). Eighty-three patients (7.8%) died of acute pancreatitis; 77 (16.1%) had necrotic disease and 6 (1.0%) edematous. There was no statistically significant difference in mortality among the etiologic groups, and no relation was found between mortality and age. Conclusion Both cholelithiasis and alcohol were main etiologic factors in the more northern countries studied, whereas cholelithiasis alone predominated in the more southern ones. Mortality was high for necrotic pancreatitis; it was similar among the various etiologic groups, and there was no relationship between mortality and age.

Effect of cessation of alcohol use on the course of pancreatic dysfunction in alcoholic pancreatitis

Exocrine pancreatic function was studied sequentially by means of the secretin-cerulein test in 32 patients with alcoholic chronic pancreatitis to elucidate the long-term course of pancreatic dysfunction, and to determine whether the cessation of alcohol use had any influence on the natural history of pancreatic functional changes caused by this disease. At initial studies, 5 patients had normal pancreatic function, and the remaining 27 had pancreatic insufficiency, which was mild to moderate in most subjects. The final studies, carried out at an average of 7.3 yr (range, 4-11 yr) after the first, showed a significant deterioration in pancreatic function, both in patients who stopped alcohol after the initial study (n = 18) and in those who did not (n = 14). The deterioration, however, was significantly less marked in patients who stopped drinking alcohol than in those who continued. These data indicate that pancreatic functional changes caused by alcoholic pancreatitis progress even after cessation of alcohol use; however, the progression is slower and less severe when alcohol intake is stopped.

Nonfunctioning Pancreatic Endocrine Tumors: A Multicenter Clinical Study

OBJECTIVES:Nonfunctioning pancreatic endocrine tumors (NFPTs) are rare neoplasms that have been the object of few studies that have involved only small numbers of patients. This study was carried out to obtain a comprehensive and up-to-date clinical picture of these tumors.METHODS:A total of 184 patients with NFPT admitted to three Italian hospitals in the last 15 yr were studied. The diagnosis of NFPT was confirmed histologically using conventional and immunohistochemical techniques. Data were obtained from the medical charts or directly from the patients.RESULTS:There were 85 men (46.2%) and 99 women (53.8%). The mean age at diagnosis was 55.2 yr (range 17–82 yr). The percentage of smokers and alcohol drinkers was similar to that in the general population. Seven patients (3.9%) had a family history of exocrine pancreatic carcinoma. In 120 cases (65.2%), the diagnosis was made after workup for pain or other symptoms, in the remaining 64 cases (34.8%), the tumor was discovered incidentally by ultrasound; in this group survival was significantly greater than it was for the symptomatic patients (p = 0.0043). Survival was also found to be improved by tumor resection (p < 0.0001), absence of metastases (p < 0.0001), and small tumor size (≤3 cm) (p < 0.0007).CONCLUSIONS:NFPTs were slightly more frequent in women and were diagnosed most often in middle-aged individuals. No risk factors other than a family history of exocrine pancreatic carcinoma were found. Tumor discovery while patients were still asymptomatic, tumor resection, absence of metastases, and tumor size ≤3 cm significantly prolonged survival.

Fecal elastase 1 determination in chronic pancreatitis

This study assessed the diagnostic accuracy offecal elastase 1 in chronic pancreatitis. Fifty-threehealthy subjects, 44 patients with chronic pancreatitis(22 severe, 13 moderate, and 9 mild), and 43 patients with nonpancreatic digestive diseasewere studied. Elastase 1 concentration was determined ona small sample of feces using a commercially availablekit. Fecal chymotrypsin was also measured. With a cutoff level of 190 μg/g, all healthycontrols except one (98.1%), and the majority ofpatients with nonpancreatic digestive diseases (40 of43; 93.0%) had elastase values above this limit. Amongthe 44 patients with chronic pancreatitis, 34(77.3%) had pathological values: all 22 (100%) withsevere disease, 10 of 13 (76.9%) with moderate diseaseand 2 of 9 (22.2%) with mild disease. Chymotrypsinvalues were pathological in 25 of 44 (56.8%) patientswith chronic pancreatitis: 17 of 22 (77.2%) with severepancreatitis, 7 of 13 (53.8%) with moderatepancreatitis, and 1 of 9 (11.1%) with mild disease. The specificity was 95.8% for elastase 1 and 85.4%for chymotrypsin. The difference both in sensitivity andspecificity of the two enzymes was statisticallysignificant (P < 0.05). Fecal elastase 1 has a high sensitivity, superior to that of fecalchymotrypsin, in the diagnosis of chronic pancreatitis.For its simplicity and rapidity, it could represent thetubeless test of choice in chronicpancreatitis.

An update on recurrent acute pancreatitis: data from five European countries

OBJECTIVE:A great number of studies have been published on acute pancreatitis, but few have focused on the recurrent form. In this study, we have sought to determine the relative frequency and mortality of recurrent acute pancreatitis, and also to update our knowledge of its etiological factors.METHODS:Patients were selected from a total of 1068 persons included in a previous European study of acute pancreatitis. All were admitted to a hospital with an attack of acute pancreatitis between January, 1990 and December, 1994. Data for each patient was recorded on a standardized form.RESULTS:Of the 1068 with acute pancreatitis, 288 (27%) had recurrent pancreatitis; the majority (78.8%) were men, with a mean age of 43 yr (range 16–95 yr). Regarding etiology, alcohol was the most frequent factor (57%), followed by gallstones (25%), other factors (7.6%), and no identified factor (10.4%). Of the 288 patients, 17 (5.9%) died, all of whom had necrotizing pancreatitis; among all of the patients with necrotizing pancreatitis (141 of 288), the mortality was 12.1%. These percentages are lower than those for patients who had a single attack (8.5% and 18.6%, respectively), but not to a statistically significant degree. Mortality was significantly lower among patients with alcoholic pancreatitis (6.9%) than among those with biliary (30%) (p < 0.002) or idiopathic pancreatitis (25%) (p < 0.04). Most of the deaths (82.4%) occurred at the second attack of pancreatitis.CONCLUSION:Acute recurrent pancreatitis remains a frequent disease, with alcohol being the most frequent etiological factor. Mortality is similar to that of a single episode of acute pancreatitis, and it is significantly lower among patients with alcohol as the etiology.

Slow-release lanreotide treatment in endocrine gastrointestinal tumors

Objectives:Lanreotide is a somatostatin analogue whose activity persists for 10–14 days. In this study, we treated a group of patients with gastrointestinal endocrine tumors with lanreotide to assess its therapeutic efficacy and tolerability.Methods:Eighteen patients, 12 male and six female, mean age 58 yr (range, 25–80 yr) were studied. Ten had carcinoid tumors, five had nonfunctioning endocrine tumors, two had glucagonomas, and the remaining one had a gastrinoma. All patients had somatostatin receptors, demonstrated by octreoscan scintigraphy. Lanreotide was administered intramuscularly at a dose of 30 mg every 10 days, for a mean of 12 months (range, 5–18 months). Fifteen of the 18 patients had been previously treated with octreotide.Results:In patients with carcinoid tumors, lanreotide markedly reduced daily bowel movements and flushing episodes. A reduction was also observed in urinary serotonin and urinary 5-hydroxyindoleacetic acid, although it was not statistically significant. A marked reduction in symptoms, and in plasma glucagon and serum gastrin levels, was also observed in patients with glucagonoma and gastrinoma. In the five patients with nonfunctioning endocrine tumors, as in all the other 13 patients, no significant effects were noted in the size of the tumor. The administration of lanreotide did not cause side effects, apart from transient abdominal pain and pain at the injection site in two patients. Only in the patient with gastrinoma was lanreotide suspended, because of the appearance of attacks of marked hypoglycemia. In the 15 patients previously treated with octreotide, no differences in the effects were noted with lanreotide.Conclusions:Lanreotide has a satisfactory therapeutic efficacy and tolerability in the treatment of gastrointestinal endocrine tumors; its effects are similar to those of octreotide. However, unlike octreotide, it can be administered once every 10–14 days, instead of 2 or 3 times daily and for this reason, it is preferable in clinical practice.

Role of serum pancreatic enzyme assays in diagnosis of pancreatic disease

The serum behavior of amylase, pancreatic isoamylase, lipase, trypsinogen, and elastase 1 was studied in 145 patients with pancreatic disease and in 66 patients with abdominal pain of nonpancreatic origin, for the purpose of evaluating the relative diagnostic utility of their assays. In 34 patients with acute pancreatitis, serum lipase, trypsinogen, and elastase 1 were elevated in all 34, pancreatic isoamylase in 33 (97%) and amylase in 30 (88%). Ten of these acute pancreatitis patients were followed sequentially for seven days: the variations in their serum enzyme levels were parallel, although the lipase, trypsinogen, and particularly the elastase 1 elevations persisted longer than did those of amylase and pancreatic isoamylase. Among the patients with chronic pancreatitis, either in painful relapse (N=19) or with pancreatic cysts (N=15), the respective percentages of enzymes elevations were: 79 and 80% for elastase 1, 68 and 67% for trypsinogen, 63 and 73% for pancreatic isoamylase, 58 and 60% for lipase, 53 and 60% for amylase. In the 52 chronic pancreatitis patients studied during clinical remission, serum enzyme behavior varied greatly, and a majority of the assays (60%) were normal; even in the case of severe pancreatic exocrine insufficiency, normal as well as abnormally high and low enzyme values were seen. Highly variable enzyme behavior was also seen in the 40 patients with pancreatic cancer, and elastase I was the most frequently (35%) elevated enzyme in this group as well. Among the patients with abdominal pain of nonpancreatic origin, abnormally high enzyme levels were present in percentages ranging from 6% for lipase to 21% for trypsinogen. These data indicate that serum pancreatic enzyme assays are of value in establishing the diagnosis of acute pancreatitis and a relapse or cystic complication of chronic pancreatitis. In the case of pancreatic cancer or of chronic pancreatitis in clinical remission, the diagnostic role of the studied enzymes is rather limited.

Coagulative disorders in human acute pancreatitis: role for the D-dimer.

Introduction and aims We investigated coagulative disorders, particularly the role of the D-dimer, in acute pancreatitis where coagulation abnormalities related to disease severity are known to occur. Methodology D-dimer levels in 30 patients with acute pancreatitis were evaluated; pancreatitis was mild and uncomplicated in 11 patients, accompanied by complications in 15, and severe in 4. We attempted to find a relationship between the D-dimer level and the antithrombin III level, prothrombin time, partial thromboplastin time, the C-reactive protein level, and results of routine laboratory tests. Results In the 11 patients with uncomplicated pancreatitis, the D-dimer level increased about 1.5 times over the limit, while in the 15 patients with complications and the four patients with severe pancreatitis, the D-dimer level increased about seven times above the normal limit; this difference was highly significant (p < 0.0001). The rise in the D-dimer level was inversely related to albumin and calcium levels (p = 0.0001) and directly related to the C-reactive protein level, fibrinogen level and leukocyte count (p = 0.0001), prothrombin time (p = 0.006), partial thromboplastin time (p = 0.03), and acute abdominal collections and lung involvement (p = 0.0001). The increase appeared early on, lasting for the entire study and peaking on days 3–6. Conclusions The D-dimer is the expression of pancreatitis and the extension of systemic involvement; it may be considered a prominent link in the chain of events leading to severe disease.

Comparative Study of Serum Pancreatic Isoamylase, Lipase, and Trypsin-Like Immunoreactivity in Pancreatic Disease

Serum total amylase, pancreatic and salivary isoamylase, lipase and trypsin-like immunoreactivity (TLI) were measured in 16 patients with acute pancreatitis, 37 patients with chronic pancreatitis, 11 patients with pancreatic cancer, and 53 control subjects in order to evaluate the relative value of these tests in the diagnosis of pancreatic disease. In acute pancreatitis patients studied within 2 days from the onset of pain all pancreatic enzymes were abnormally high. In chronic pancreatitis patients serum pancreatic isoamylase and TLI were abnormally low in 8 out of 10 patients with severely impaired pancreatic exocrine function, while lipase was abnormally low in 6 patients. During acute exacerbations of the disease elevated levels of pancreatic isoamylase and lipase, but not of TLI, were found in about one third of cases. In patients with pancreatic cancer the pattern of changes in serum pancreatic enzymes was variable since levels within, below and above the normal range were found. The results demonstrate that in acute pancreatitis all serum pancreatic enzymes had the same diagnostic sensitivity, however serum lipase determination is the most convenient because of its simplicity and low cost. In chronic pancreatitis serum pancreatic isoamylase and TLI may be useful in detecting severe pancreatic insufficiency. In pancreatic cancer serum pancreatic enzymes lack diagnostic specificity.

Mutations of the CFTR gene in pancreatic disease.

Introduction An association has been found between CFTR gene mutations and chronic pancreatitis; however, there is a lack of information about the frequency of CFTR gene mutations in acute pancreatitis and in pancreatic cancer. Aim To prospectively evaluate the prevalence of CFTR gene mutations in acute pancreatitis, chronic pancreatitis, and pancreatic cancer. Methodology Ninety-eight consecutive patients were studied and divided into 3 groups: 34 patients with acute pancreatitis, 46 patients with chronic pancreatitis, and 18 patients with pancreatic cancer. The mutation analysis of the CFTR gene was carried out using diagnostic commercial kits for the simultaneous detection of 29 mutations and Tn polymorphism. Results Among the 98 patients studied, 12 (12.2%) had CFTR gene mutations: 2 of the 34 patients (5.9%) with acute pancreatitis, 9 of the 46 (19.6%) with chronic pancreatitis, and 1 of the 18 (5.6%) with pancreatic cancer. All the mutations were found in heterozygosis (2 &Dgr;F508, 1 W1282X, and 9 T5 allele). Conclusion Our prospective study adds further information about the frequency of CFTR mutations in patients with a single episode of acute pancreatitis. Furthermore, our results suggest an association of CFTR gene mutations with chronic alcoholic pancreatitis and emphasize the need for a multicenter study, possibly multinational, to conclusively establish the role of CFTR mutations as a genetic susceptibility factor for this disease.