J. Enrique Domínguez-Muñoz

Validity of a modified 13C-urea breath test for pre- and posttreatment diagnosis of Helicobacter pylori infection in the routine clinical setting

OBJECTIVE:Citric acid meets the criteria of an optimal test drink for the 13C-urea breath test (13C-UBT) because it permits rapid, high level recovery of the 13C administered. In a previous study we reported that administration of 13C-urea dissolved in a citric acid solution provides results similar to those obtained with standard administration of the substrate 10 min after the test drink. The aim of this study was to evaluate the accuracy of this modified 13C-UBT for both primary and posttreatment diagnosis of Helicobacter pylori (H. pylori) infection in a large patient population in clinical practice.METHODS:The 13C-UBT was performed in 553 patients with dyspeptic symptoms by giving them 75 mg of 13C-urea either 10 min after administration of 200 ml of a test drink comprising 0.1 mol/L citric acid solution (protocol 1, n = 320) or dissolved in the same amount of this test drink (protocol 2, n = 233). All patients underwent an upper gastrointestinal endoscopy and the H. pylori-status was assessed by histology, rapid urease test, and culture. Sixty patients with proven H. pylori infection were reinvestigated by both endoscopy and 13C-UBT (protocol 2) 4 wk after completing eradication therapy.RESULTS:The accuracy of the two test protocols in the pretreatment diagnosis of H. pylori infection (95.6% and 96.6%), as well as of the modified 13C-UBT in the posttreatment evaluation of the infection (98.3%) was similar. More meaningful are the high PPV (>96%) and NPV (>93%) of the 13C-UBT under pre- and posttreatment conditions.CONCLUSIONS:The administration of 13C-urea dissolved in a citric acid solution simplifies the 13C-UBT, while preserving the high accuracy in the diagnosis of H. pylori infection. This modified 13C-UBT has equal accuracy in the pre- and the posttreatment situations.

Monitoring of serum proteinase-antiproteinase balance and systemic inflammatory response in prognostic evaluation of acute pancreatitis : results of a prospective multicenter study

With the aim of studying the clinical usefulness and applicability of circulating levels of protease inhibitors, complement factors, acute phase reactants, and leukocytic enzymes in the prognostic evaluation of acute pancreatitis (AP), the present prospective multicenter study has been carried out. A total of 182 patients with AP have been included, to whom an exhaustive evolutive protocol has been applied from the time of their hospital admission (2–12 hr from the onset of the disease) until the 15th day of evolution in order to clearly define them. The severe episodes exhibit a greater consumption of α2-macroglobulin, and C3 and C4 complement factors, as well as a greater increase of α1-protease inhibitor, C-reactive protein and polymorphonuclear elastase than mild events, with regards to the underlying pathophysiological condition. The determination of the plasma levels of leukocytic elastase in the first hours of evolution allows a prediction of the severity of the acute pancreatitis event with a high reliability (predictive values that become higher than 90%). The clinical value of the remaining parameters analyzed, in this aspect, is less, being applicable to the monitoring of the disease.

Interdigestive cycling in chronic pancreatitis: Altered coordination among pancreatic secretion, motility, and hormones

BACKGROUND & AIMSnSecretions from the exocrine and endocrine pancreas may modulate interdigestive motility. To test this hypothesis in humans, we investigated interdigestive cycling in patients with chronic pancreatitis (CP) as a model of impaired pancreatic function.nnnMETHODSnAntroduodenal motility, pancreatic enzyme output, and pancreatic polypeptide release were monitored for two consecutive interdigestive cycles in 13 controls and 9 patients with CP.nnnRESULTSnInterdigestive enzyme output was severely impaired in patients with CP (> 80% decrease); however, secretory cycling was still evident in most patients. All parameters describing interdigestive motility were similar in controls and patients with CP (duration of the migrating motor complex [MMC] was 107 +/- 19 minutes in patients with CP vs. 114 +/- 15 minutes in controls). The time between cyclic peaks of enzyme secretion (76 +/- 4 minutes vs. 101 +/- 4 minutes in controls) and pancreatic polypeptide (63 +/- 4 minutes vs. 106 +/- 7 minutes in controls) was shortened in patients with CP, and peaks were no longer temporally related to the MMC. Only 56% of phase III activity fronts were associated with a concomitant secretory peak in patients with CP compared with 92% in healthy subjects.nnnCONCLUSIONSnCP not only decreases pancreatic secretion but interrupts the coordination among interdigestive cyclic phenomena. Our findings in several animal and human models refute the concept that pancreatic mechanisms exert a major regulatory influence on interdigestive motor activity.

M1-muscarinic mechanisms regulate interdigestive cycling of motor and secretory activity in human upper gut

We determined the influence of M1-muscarinic pathways in modulating temporal cycling of motor and secretory activity in the fasting upper gut. Eight healthy subjects were studied on two separate days, following a double-blind, randomized protocol. Antroduodenal motility (migrating motor complex, MMC), pancreatic exocrine secretion (amylase, lipase, trypsin, chymotrypsin), and plasma levels of associated hormones [motilin, pancreatic polypeptide (PP)] were monitored for two consecutive cycles during background infusion of placebo or telenzepine, a selective M1-muscarinic receptor antagonist. On placebo days, pancreatic enzymes and hormones cycled in synchrony with motor activity, as expected. During M1 blockade, duodenal output of each enzyme was decreased by 85–90% in phase I and by >90% in phase III. Similarly, plasma concentrations of hormones were decreased during all phases and cycling was absent. Despite the loss of these putative influences, intestinal motility continued to cycle, albeit in an altered fashion. Intermittent phase II activity was replaced by phase I quiescence, while phase III-like fronts were diminished (contraction frequency, amplitude, propagation velocity reduced 30–60%, duration not altered) but recurred at expected intervals (cycle length 105±14 min vs 109±12 in placebo). Gastric motor activity was virtually abolished. These data suggest or extend several working hypotheses: (1) Motilin is released and/or acts via cholinergic (M1-muscarinic) pathways to initiate antral, but not duodenal, phase III activity. (2) M1 receptors mediate all components of the gastric MMC and phase II activity throughout the gut, but intestinal phase III activity arises via alternate pathways. (3) M1-muscarinic mechanisms regulate interdigestive cycling of pancreatic enzymes and PP. (4) Secretions from the endocrine/exocrine pancreas are not primary mediators of intestinal motility.

Prevalence of Helicobacter pylori infection and gastric mucosal abnormalities in chronic pancreatitis

Objective:Chronic pancreatitis is often associated with abnormal gastric acid secretion. However, previous studies have taken into consideration neither the potential role of Helicobacter pylori (H. pylori) infection nor histological features of the gastric mucosa in this context. The aim of this study was to analyze the prevalence of H. pylori infection as well as the pattern of gastritis in patients with chronic pancreatitis.Methods:Forty patients with chronic alcoholic pancreatitis were included in the study: 40 patients with alcoholic liver cirrhosis and normal exocrine pancreatic function and 40 asymptomatic nonalcoholic subjects matched for age and sex used as control subjects. Endoscopy was performed in all patients, and five biopsy specimens from the antrum (three from the gastric body and two from the cardia) were taken for histological grading of gastritis and H. pylori assessment.Results:Prevalence of H. pylori infection was similar in subjects with chronic pancreatitis (38%), asymptomatic subjects (28%) and liver cirrhosis (30%). Topography and expression of H. pylori-associated chronic gastritis was also not different among the three groups of subjects. In H. pylori-negative subjects, the presence of moderate to severe chronic antral gastritis was significantly more common in patients with chronic pancreatitis (40%) than in subjects with liver cirrhosis (18%) and in asymptomatic subjects (14%) (p < 0.05). No difference was found among the three groups of patients with regard to gastritis activity, atrophy, and intestinal metaplasia in the various gastric regions. The chronicity grade of gastritis did not correlate with the severity of pancreatic insufficiency.Conclusion:Prevalence of H. pylori infection is not different in patients with chronic pancreatitis as compared with subjects alcoholic liver cirrhosis and asymptomatic subjects. A severe H. pylori-negative chronic gastritis is more common in patients with chronic pancreatitis. This chronic inflammation of the gastric mucosa could contribute to determining the changes in gastric physiology described in patients with chronic pancreatitis.

Potential for Screening for Pancreatic Exocrine Insufficiency Using the Fecal Elastase-1 Test

The early diagnosis of pancreatic exocrine insufficiency (PEI) is hindered because many of the functional diagnostic techniques used are expensive and require specialized facilities, which prevent their widespread availability. We have reviewed current evidence in order to compare the utility of these functional diagnostic techniques with the fecal elastase-1 (FE-1) test in the following three scenarios: screening for PEI in patients presenting with symptoms suggestive of pancreatic disease, such as abdominal pain or diarrhea; determining the presence of PEI in patients with an established diagnosis of pancreatic disease, such as chronic pancreatitis or cystic fibrosis; determining exocrine status in disorders not commonly tested for PEI, but which have a known association with this disorder. Evidence suggests the FE-1 test is reliable for the evaluation of pancreatic function in many pancreatic and non-pancreatic disorders. It is non-invasive, is less time-consuming, and is unaffected by pancreatic enzyme replacement therapy. Although it cannot be considered the gold-standard method for the functional diagnosis of PEI, the advantages of the FE-1 test make it a very appropriate test for screening patients who may be at risk of this disorder.

Targeting the Abnormalities of Gastroduodenal Functions in Functional Dyspepsia

The current definition of functional dyspepsia changes the previous concept of absence of organic disease to the presence of a functional alteration of the upper gastrointestinal tract. From a theoretical point of view, the alteration of any major gastrointestinal function may induce dyspeptic symptoms. However, both asymptomatic subjects with some gastrointestinal functional alteration and dyspeptic patients without a demonstrable dysfunction are not unusual. This may be explained at least in part by the more recent concept of visceral sensitivity. The potential role of acid secretion in the pathogenesis of functional dyspepsia as well as the positive effect of antisecretory drugs in a proportion of patients may be based on an increased gastric acid secretion and duodenal acid overload, a hypersensitivity to acid and/or the development of acid-mediated gastrointestinal motor abnormalities. Helicobacter pylori infection may play a role in this context. Both interdigestive and postprandial gastrointestinal motility, mainly a delayed gastric emptying and an altered intragastric distribution of nutrients, have been described to be disturbed in up to half of the patients with functional dyspepsia. This may also be an explanation for the high frequency of intestinal bacterial overgrowth in these patients. Most probably, visceral hypersensitivity should be present for motor alterations to induce symptoms. This is the basis for future development of new drugs in the management of this functional syndrome. The role of H. pylori in the pathogenesis of functional dyspepsia is a matter of discussion, but a proportion of patients benefit from eradication therapy and, therefore this therapeutic approach should be taken into account.

Assessment of the fibrogenetic activity in chronic pancreatitis

SummaryDetermination of circulating levels of extracellular matrix components has been proposed as a reliable method to assess the activity of fibrogenetic processes. Therefore, we aimed to analyze circulating levels of laminin, fibronectin, and procollagen III peptide (PIIIP) in patients with chronic pancreatitis (CP) and to correlate them with the morphological and functional stage, and duration of the disease. Thirty patients with CP and 18 healthy controls were studied. Serum PIIIP concentrations (RIA), but not fibronectin (RID) and laminin (RIA), were abnormally high in 8 patients with CP. No correlation was found between circulating levels of extracellular matrix components and both functional and morphological stage and duration of CP. Nevertheless, patients with elevated serum PIIIP levels tend to have a more advanced CP (morphological and functional changes) than those with normal levels after a similar duration of the disease. We hypothesize that whereas functional and morphological findings reflect the cumulative effect of chronic inflammation on the pancreas, serum PIIIP concentrations would reflect the activity of the fibrogenetic process within the gland at the time of sampling. The results shown in the present study may be considered a starting point for longitudinal studies that examine the relationship between serum PIIIP or other markers for fibrogenetic activity and evolution of CP.