A study of pancreatic function among subjects over ninety years of age.

BACKGROUND: Among the various studies of pancreatic function in the elderly published so far, none have dealt with subjects over 90 years of age. The aim of this study was to examine pancreatic function in healthy individuals over 90 years old. METHODS: Sixty-eight healthy noninstitutionalized elderly persons, aged 91-104 years, with a mean age of 95 years, and 63 younger controls were studied. Pancreatic function was studied by determining fecal elastase 1 concentration. In addition to this test, we also measured serum amylase, pancreatic isoamylase and lipase in 53 of the 68 elderly subjects. RESULTS: All but 1 of the 68 elderly subjects had normal elastase 1 values; the one who did not had a value slightly below normal. No significant difference with controls was found. Serum pancreatic enzymes were normal in almost all of the 53 elderly studied; 3 had a mild elevation only of amylase and 1 had a persistent elevation of amylase, pancreatic isoamylase and lipase. CONCLUSIONS: In subjects over 90 years of age, exocrine pancreatic function continues to be normal; if an impairment occurs, it is mild and not significant for digestion of food. In addition, serum pancreatic enzymes remain within normal limits in the vast majority of cases.

[Benign pancreatic hyperenzynemia or Gullo's syndrome]. / Iperenzimemia pancreatica benigna o sindrome di Gullo.

Benign pancreatic hyperenzymemia is a newly identified syndrome characterized by abnormal increase in serum pancreatic enzymes in absence of pancreatic disease. The hyperenzymemia can occur sporadically or in a familial form, and all of the pancreatic enzymes show elevations. Although the condition is persistent, the enzyme elevations fluctuate considerably, even temporarily returning to normal levels at times. In this paper the main characteristics of this syndrome are described.

Day-to-day variations of serum pancreatic enzymes in benign pancreatic hyperenzymemia.

BACKGROUND & AIMS: Benign pancreatic hyperenzymemia is a newly identified syndrome that is characterized by a chronic increase of serum pancreatic enzymes in the absence of pancreatic disease. When checked at intervals of months or years, the enzyme levels show considerable variation from one test to another, and enzyme normalization is sometimes seen. The purpose of this study was to determine whether these variations can occur on a day-to-day basis. METHODS: Forty-two subjects with benign pancreatic hyperenzymemia, 28 men and 14 women, mean age 50 years, range 16-68 years, were studied. In each subject serum amylase, pancreatic isoamylase, and lipase levels were determined once daily on each of 5 consecutive days; in 15 of the 42 subjects studied, serum trypsin level was also measured. RESULTS: In 8 (19%) of the 42 subjects, the serum enzyme levels were abnormally elevated for all 5 days of the study but showed wide fluctuations. In 33 (78.6%) subjects, the hyperenzymemia showed considerable day-to-day variations that included normalizations. In the remaining subject (2.4%), all enzymes were normal. In most of the subjects with hyperenzymemia, 37 of 41, all enzyme levels were elevated, with lipase, and trypsin when performed, showing the highest values. Of the remaining 4 subjects, in 3 only amylase and pancreatic isoamylase were increased and in 1 only lipase. CONCLUSIONS: The results show that there are marked day-to-day variations, with frequent normalizations, of serum enzyme levels in subjects with benign pancreatic hyperenzymemia. The reason for these wide day-to-day fluctuations is not known.

'Do research with seriousness and perseverance'. An interview with Prof. Lucio Gullo. Interview by Martin E. Fernandez-Zapico.

In the current interview Prof. Lucio Gullo, a worldwide-recognized pancreatologist for his contribution on the understanding of the pathogenesis and clinical aspects of a number of pancreatic diseases including benign pancreatic hyperenzymemia, shares with Pancreatology his life experiences as a scientist in pancreatic research.

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 intravenous infusion of amino acids on pancreatic secretion.

BACKGROUND/AIMS: The effect of intravenous administration of amino acids on exocrine pancreatic secretion is controversial. Since amino acids are used in parenteral nutrition of patients with acute pancreatitis or other pancreatic diseases, it seemed useful to establish whether or not they affect pancreatic secretion. METHODOLOGY: Four patients having an external transduodenal drainage of the main pancreatic duct performed after sphincteroplasty for common bile duct stones were studied. Two of them had undergone a Billroth II gastrectomy in the past. Pancreatic secretion was stimulated with low doses of secretin (0.1 CU/kg/h) and cerulein (10 ng/kg/h); after 75 min of stimulation, when pancreatic secretion was stable, a solution of L-amino acids (Freamine III 8.5%) was infused intravenously at a rate of 150 mL/h, for two hours. The volume of pancreatic secretion, bicarbonate and total protein was measured. RESULTS: The infusion of amino acids did not cause significant changes in pancreatic secretion. However, considering the results individually, they caused a clear increase of pancreatic secretion, mainly of bicarbonates (mean increase of 36%) in the two subjects who had not undergone previous surgical procedures and no increase in the two who had had a Billroth II gastrectomy. CONCLUSIONS: The results suggest that intravenous administration of amino acids stimulates exocrine pancreatic secretion in normal subjects but not in those who underwent previous gastrectomy. This stimulatory effect could be mediated by stimulation of gastric acid. This effect should be taken into consideration when amino acids are used in patients with acute pancreatitis or other pancreatic disorders.

Magnetic resonance cholangiopancreatography in asymptomatic pancreatic hyperenzymemia.

OBJECTIVES: To determine the type and frequency of pancreatic lesions detected by magnetic resonance cholangiopancreatography (MRCP) in subjects with asymptomatic pancreatic hyperenzymemia and to assess for a possible relationship between these lesions and the hyperenzymemia. METHODS: From January 2005 to May 2008, 63 subjects with asymptomatic pancreatic hyperenzymemia were studied by MRCP. In addition, amylase, pancreatic isoamylase, and lipase were determined for 5 consecutive days. RESULTS: In most subjects (n = 57, 90.5%), MRCP showed a normal pancreas. In the remaining 6 subjects (9.5%), the following alterations were found: pancreas divisum in 2, small intrapancreatic cyst in 2, anatomic variant of the Wirsung in 1, and mild dilatation of 3 secondary ducts in 1. In these 6 subjects, hyperenzymemia was highly variable from day to day, with frequent normalizations, as was also true for the 30 subjects with no MRCP alterations in whom diurnal enzyme determinations were made. CONCLUSIONS: Most of the subjects with asymptomatic pancreatic hyperenzymemia did not have pancreatic lesions detectable by MRCP. In the few subjects in whom a lesion was found, the great variability and the frequent transient normalization of serum enzyme levels tend to exclude a relation between the lesion and the hyperenzymemia.

SPINK1 and PRSS1 mutations in benign pancreatic hyperenzymemia.

UNLABELLED: The aim of this study was to determine whether mutations in SPINK1/PRSS1 genes are associated with benign pancreatic hyperenzymemia (BPH). METHODS: Sixty-eight subjects with BPH (including 13 familial cases) were studied. In all, we sequenced germline DNA for all the exons and intro-exon boundaries of PRSS1 and SPINK1. RESULTS: Nine (13.2%) of the 68 subjects harbored PRSS1 or SPINK1 mutations. As to PRSS1, no hereditary pancreatitis-associated variant was detected, whereas previously undescribed mutations (p.Ala148Val and c.40+1G>A) were respectively found in 2 subjects (2.9%). SPINK1 mutations were detected in 7 subjects (10.3%). Five of them exhibited known mutations (3 p.Asn34Ser, 1 p.Pro55Ser, and 1 c.88-23A>T), whereas 2 had a newly found variant (p.Arg67Gly and c.*32C>T, respectively). Only 2 familial BPH, belonging to 2 different families, were found to carry a mutation (1 with p.Ala148Val for PRSS1 and 1 with p.Asn34Ser for SPINK1). CONCLUSIONS: No known mutations of PRSS1 have been found in BPH, whereas the frequency of known SPINK1 variants is similar to that reported in the general population. No segregation of PRSS1/SPINK1 variants occurs in BPH families. Benign pancreatic hyperenzymemia cannot be explained by mutations in genes whose variants are known to be associated with pancreatitis or by mutations in other PRSS1/SPINK1 genes.

Benign pancreatic hyperenzymemia in children.

One of us recently described chronic pancreatic hyperenzymemia in the absence of pancreatic or other disease in adult subjects. The aim of the present study was to describe this form of pancreatic hyperenzymemia in children. The study involved 15 children with this condition seen from September 1996 to December 2004. After initial evaluation, each child was seen by us once annually until the end of the study. Each check-up included serum amylase (normal values 20-220 IU/L), pancreatic isoamylase (17-115 IU/L) and lipase (24-270 IU/L) determinations as well as abdominal ultrasound. In six children, fecal elastase was also determined. At the initial assessment, 13 of the 15 children had abnormal serum increases in all three enzymes, one showed an increase only in lipase, and in the remaining child all three enzymes were present in normal concentrations. These latter two children had had abnormally elevated levels of all enzymes at the examination performed before this study began. During follow-up, enzyme concentrations remained abnormally elevated, although with wide fluctuations and transient normalizations. Considering the highest values of enzymes found in the various examinations performed during this study, the increase over the upper normal limit was in the range of 1.5- to 5.2-fold for amylase, 2.2-to 8.0-fold for pancreatic isoamylase, and 2.0- to 15.4-fold for lipase. Fecal elastase was normal in the six children in whom it was measured. No child had evidence of pancreatic or other disease, either at initial evaluation or during follow-up. The results of this study describe benign pancreatic hyperenzymemia in children. Although it is a benign condition, awareness of it is important to avoid unnecessary concern and multiple diagnostic procedures.

Quality of life and clinical indicators for chronic pancreatitis patients in a 2-year follow-up study.

OBJECTIVES: There are no data available that evaluate the possible modifications of the quality of life during the clinical course of chronic pancreatitis. To evaluate the outcome for patients with chronic pancreatitis in a 2-year follow-up study. METHODS: The Short Form 12 Health Survey Italian version questionnaire was used for the purpose of the study. The questionnaire generates 2 summary scores: the physical component summary (PCS-12) and the mental component summary (MCS-12). Eighty-three patients with chronic pancreatitis were studied with a mean (+/-SD) interval time of 2.3 +/- 0.2 years between the first and the second evaluation. RESULTS: There was a significant increase in the frequency of diabetes mellitus (P = 0.008), nonpancreatic surgery (P = 0.016), and comorbidities (P = 0.004). The PCS-12 (44.7 +/- 10.7) and MCS-12 (44.1 +/- 13.3) were not significantly different in comparison with the baseline evaluation (PCS-12, 43.7 +/- 9.8; MCS-12, 44.3 +/- 11.4). The PCS-12 score worsened in 17 (20.5%) patients, 44 (53.0%) had a stable PCS-12 score, and the remaining 22 (26.5%) improved their PCS-12 score. Regarding the mental score, 15 (18.1%) patients worsened, 52 (62.7%) had a stable MCS-12 score, and the remaining 16 (19.3%) improved their MCS-12 score. Only age at diagnosis was significantly related to the change of the MCS-12 score (P = 0.028, positive relationship). CONCLUSIONS: The information given by quality-of-life assessment should be routinely included in the work-up of patients affected by chronic pancreatitis to select those patients with severely impaired physical and mental scores, and to plan an intensive program of medical and psychological follow-up.

Can pancreatic steatosis explain the finding of pancreatic hyperenzymemia in subjects with dyslipidemia?

OBJECTIVE: It has been proposed by some investigators that benign pancreatic hyperenzymemia could result from pancreatic steatosis that they believe would have been caused by dyslipidemia; their diagnosis of steatosis was based on the finding of a hyperechogenic pancreas at ultrasound. The aim of this study was to assess the validity of this proposed model. METHODS: The study group was composed of 18 subjects with benign pancreatic hyperenzymemia, 12 men and 6 women; mean age, 55 years; range, 38 to 68 years. All 18 had dyslipidemia and 9 had hyperechogenic pancreas at ultrasound. In addition, 6 subjects with benign pancreatic hyperenzymemia but who did not have dyslipidemia or hyperechogenic pancreas and 10 healthy subjects with none of these conditions were also studied as controls. In each of these subjects, magnetic resonance imaging of the pancreas was performed to assess the presence of pancreatic steatosis. RESULTS: Magnetic resonance imaging showed normal pancreas with no signs of fatty infiltration in all 18 subjects with dyslipidemia, including those with both dyslipidemia and hyperechogenic pancreas at ultrasound. A similar result was found in all control subjects. CONCLUSION: The finding of a completely normal pancreas at magnetic resonance imaging does not support the proposed model in which pancreatic hyperenzymemia in subjects with dyslipidemia is attributed to pancreatic steatosis.

A search for acute necrotic pancreatitis in early stages of alcoholic chronic pancreatitis.

OBJECTIVES: Various investigators believe that alcoholic chronic pancreatitis is the result of recurrent episodes of acute necrotic pancreatitis. The aim of this work is to study pancreatic histology in early stages of the disease to search for evidence of these acute episodes. STUDY: Of about 650 patients with alcoholic pancreatitis seen during the 30-year period from 1972 to 2002, 45 underwent surgery for this disease, all within 2 years of clinical onset. Of these 45, tissue samples adequate for study were obtained from 42, and this was the study material. Tissue samples were prepared for histologic examination by standard procedures. RESULTS: Areas of pancreatic necrosis were seen in tissue samples of only three (7%) of the 42 patients, and in all three cases chronic lesions were also present. No evidence of localized scarring that could be attributed to prior episodes of focal necrotic pancreatitis was found. A typical feature was the patchy distribution of the lesions in largely normal pancreatic tissue. The main lesions observed were perilobular and intralobular fibrosis, dilation of acini and ducts, and protein plugs in dilated ducts surrounded by periductal fibrosis. CONCLUSIONS: This study shows that, in the early stages of alcoholic chronic pancreatitis, signs of acute necrotic pancreatitis are very infrequent and, when present, they are associated with chronic lesions. These findings suggest that alcoholic pancreatitis begins as a chronic disease.

Alcoholic pancreatitis: new insights into an old disease.

Alcoholic pancreatitis is an old disease that continues to present controversial issues. One of the most hotly debated issues is whether alcoholic pancreatitis is a chronic disease from the beginning or if instead it becomes chronic after repeated episodes of acute pancreatitis. Histologic studies, including very large series of patients with alcoholic pancreatitis, have clearly shown that this disease is chronic from the beginning and that, if acute necrotic pancreatitis occurs, it is associated with chronic lesions. The possibility that acute alcoholic pancreatitis can occur in the absence of chronic lesions cannot be excluded, but, if this occurs, it is rare. In addition to alcohol, genetic factors certainly play a determining role. Until now many genetic studies have been made on chronic pancreatitis; the first dealt with hereditary pancreatitis. In this disease it has been shown that mutations of the cationic trypsinogen gene and of SPINK1 are implicated in its pathogenesis. Concerning alcoholic pancreatitis, several studies have been made, but the results so far are disappointing.

Mutations of the CFTR gene in idiopathic pancreatic hyperenzymemia.

OBJECTIVES: Idiopathic pancreatic hyperenzymemia is a new syndrome that is characterized by a chronic increase of serum pancreatic enzymes in the absence of pancreatic disease. The aim of this study was to assess whether mutations of the cystic fibrosis transmembrane conductance regulator (CFTR) gene may have a role in the etiology of this hyperenzymemia. METHODS: Seventy subjects with idiopathic pancreatic hyperenzymemia, 44 men and 26 women (mean age, 48 years; range, 8-74 years), were studied. Thirteen of these 70 subjects had the familial form of the syndrome. 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 70 subjects studied, 7 (10.0%) had CFTR gene mutations. None of these 7 subjects had the familial form of pancreatic hyperenzymemia. These mutations were DeltaF 508 in 1 subject, 2789 + 5 G > A in another subject, and T5 allele in the remaining 5. All these mutations were heterozygous, with the exception of 1 T5 allele that was homozygous in 1 subject. CONCLUSIONS: The frequencies of the mutations of the CFTR gene found in these subjects are similar to the carrier frequencies in the general Italian population. This finding does not support a role for CFTR gene mutations in the etiology of idiopathic pancreatic hyperenzymemia.

Obesity and the risk of pancreatic cancer: an italian multicenter study.

OBJECTIVE: The purpose of this work was to determine whether obesity is a risk factor for pancreatic cancer. METHODS: We studied 400 patients with this tumor and 400 controls matched for sex and age from various Italian cities. We used a standardized questionnaire that was compiled at personal interview, with particular attention to body weight at the time of the interview, and for those with the tumor, their weight before onset of the disease. Body mass index (BMI) was calculated as the patient's weight in kilograms divided by their height in meters squared. RESULTS: The risk of pancreatic cancer adjusted for smoking was 5-fold higher (P < 0.001) in patients with a BMI less than 23 kg/m2 after diagnosis compared with patients with a BMI ranging from 23 to 29.9 kg/m2, whereas the risk in patients with BMI of at least 30 kg/m2 was not significant (P = 0.689). Taking into account BMI before diagnosis, smoking was confirmed as a significant risk factor (odds ratio = 1.68; P = 0.001) for pancreatic cancer, whereas no significant relationship was found between BMI classes and the risk of pancreatic cancer (P = 0.984). CONCLUSIONS: These findings indicate that obesity is not a risk factor for pancreatic cancer.

Exocrine pancreatic function after alcoholic or biliary acute pancreatitis.

OBJECTIVES: There have been various studies of exocrine pancreatic function after acute pancreatitis, but few have examined the relationship between this function and the etiology of the pancreatitis. The aim of this work was to study pancreatic function in patients who had had acute alcoholic or acute biliary pancreatitis. METHODS: Seventy-five patients who had had a single attack of acute pancreatitis were studied. The etiology was alcohol in 36 and cholelithiasis in 39. Pancreatic function was studied between 4 and 18 months after pancreatitis by duodenal intubation in 18 patients (8 alcohol, 10 lithiasis) and by the amino acid consumption test (AACT) in the remaining 57 (28 alcohol, 29 lithiasis). For those who underwent AACT, the test was repeated 1 year after the first examination. RESULTS: Among the 36 patients with alcoholic pancreatitis, most had impaired pancreatic function at both duodenal intubation (8/8, 100%) and at AACT (22/28, 78.6%); at the second test, the AACT remained pathological (18/23, 82.1%). Of the 39 patients with biliary pancreatitis, only 4 of the 10 (40%) who underwent duodenal intubation and only 5 of the 29 (17.2%) who performed AACT had pancreatic insufficiency; at the second test, only 4 of the 26 (15.4%) who repeated the AACT were pathological. The differences in the frequency and degree of pancreatic insufficiency between patients with alcoholic and those with biliary pancreatitis were statistically significant. CONCLUSIONS: The results show that after alcoholic acute pancreatitis, the pancreatic insufficiency was significantly more frequent and more severe than after biliary pancreatitis. These findings together with the fact that the insufficiency was also more persistent suggest that acute alcoholic pancreatitis may occur in a pancreas that already has chronic lesions.