O. Pieramico

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

BACKGROUND & AIMS Secretions 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. METHODS Antroduodenal motility, pancreatic enzyme output, and pancreatic polypeptide release were monitored for two consecutive interdigestive cycles in 13 controls and 9 patients with CP. RESULTS Interdigestive 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. CONCLUSIONS CP 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.

Dopamine interrupts gastrointestinal fed motility pattern in humans: Effect on motilin and somatostatin blood levels

The aim of this study was to investigate the hypothesis that during the postprandial period in humans, dopamine interrupts the gastrointestinal motility pattern through a mechanism that is peptide-mediated. Fourteen normal human subjects were studied by means of intestinal manometry. After recording two consecutive migrating motor complexes a 900-kcal solid-liquid meal was given. In eight subjects 30 min after the meal, placebo or dopamine (5 μg/kg/min) was infused for 15 min and then the recording continued for 120 min. In the remaining six subjects dopamine was administered twice with a 90-min interval in between. In three subjects the first dopamine infusion after the meal was preceded by treatment with placebo, the second by domperidone (20 mg intravenous as bolus), in the other three subjects domperidone was given before the first dopamine infusion. Blood samples for the determination of somatostatin and motilin were drawn basally, during, and immediately after dopamine in seven subjects. The results show that dopamine interrupts the fed motility pattern, inhibiting the high antrat waves, and activates a duodenal phase III of migrating motor complexes. The pretreatment with domperidone completely prevented the dopamine effect. Plasma levels of motilin increased significantly during dopamine, while somatostatin blood levels did not change. These findings support the hypothesis that a dopaminergic mechanism may modulate the cycling of duodenal motor complex in humans.

Proximal Gastric Motility Functions Are Normal in Severe Obesity

The role of altered gastric motor functions for the development of obesity is still unclear. In this study, we investigated whether severe obesity is related to gastric dysfunctions or to abnormal perception in response to distension. 31 obese patients and 20 healthy volunteers were studied using an electronic barostat. Basal gastric tone, gastric accommodation, and perception in response to distension were not altered in obese patients. The median minimal distending pressure, reflecting the intra-abdominal pressure, was significantly elevated in obese patients, being 12 versus 7 mm Hg, respectively (p < 0.0001). We conclude that the proximal gastric motility, including perception and accommodation in response to intragastric distension, is not impaired in severe obesity. Whether disturbances of gastric reflex relaxation in response to a meal are involved in the pathogenesis of obesity remains to be established.

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.

Gastric Hypersensitivity in Nonulcer Dyspepsia An Inconsistent Finding

Visceral hypersensitivity is claimed to beinvolved in the pathogenesis of nonulcer dyspepsia(NUD). We evaluated whether gastric hypersensitivity isa consistent finding in an unselected group of NUDpatients. In 11 patients and 20 healthy controls, astandardized gastric distension was performed using agastric barostat. Perception was scored by aquestionnaire and compared between the two groups. Therewas a linear pressure/volume relationship duringgastric distension in both groups. The pain threshold inNUD patients was significantly lower compared tocontrols [5.5 ± 4.0 mm Hg above minimaldistending pressure (mdp) and 10.2 ± 2.2 mm Hg above mdp,respectively, P < 0.004], irrespective of the H.pylori status. However, more than 50% of the NUDperception scores were in the control range at mostdistension levels. Gastric hypersensitivity could be confirmed inNUD patients as a group. However, there is aconsiderable overlap concerning perception in responseto distension between unselected NUD patients andcontrols.

Ratios of Different Serum Pancreatic Enzymes in the Diagnosis and Staging of Chronic Pancreatitis

The aim of this study was to define an optimum serum enzyme ratio for the diagnosis of chronic pancreatitis (CP) and for the evaluation of the stage of the disease. With this goal in mind, a simultaneous and interrelated analysis of different serum pancreatic enzymes was performed in 296 consecutive patients with clinically suspected CP. A total of 167 patients were finally diagnosed with CP and 129 with other digestive diseases (used as controls). Serum values of pancreatic amylase, lipase, immunoreactive trypsin, and their ratios were determined in every patient before final diagnosis was established. Stepwise logistic regression analysis was performed. As expected, abnormally low values of individual serum pancreatic enzymes in the diagnosis of CP were highly specific (92-98%) but very insensitive (20-32%). Their diagnostic usefulness was neither improved by calculation of their ratios nor by the use of multivariate logistic regression analysis. A low pancreatic amylase/lipase ratio correlated with advanced CP (p < 0.01), and had a high degree of accuracy (80.5%) in the evaluation of the stage of the disease (assessed by endoscopic retrograde pancreatography). In conclusion, while serum pancreatic enzymes have limited usefulness in the diagnosis of CP, the pancreatic amylase/lipase ratio could be a simple method for staging the disease.

Omeprazole-based dual and triple therapy for the treatment of Helicobacter pylori infection in peptic ulcer disease: a randomized trial.

It was our goal to evaluate the efficacy and safety and patient compliance with omeprazole‐based dual and triple therapy for eradication of Helicobacter pylori in peptic ulcer disease.

Gallbladder dynamics in chronic pancreatitis : relationship to exocrine pancreatic function, CCK, and PP release

Gallbladder dynamics, cholecystokinin (CCK), and pancreatic polypeptide (PP) release were studied in 14 patients with chronic pancreatitis (CP) (2 females, 12 males; age range 24–56 years) and 12 control subjects (4 females, 8 males, 21–50 years). On day 1, gallbladder contractility was investigated after ceruletide intravenous infusion (2.5 ng/kg/min for 10 min). On day 2, a mixed standard test meal (1450 kJ) was administered orally. Gallbladder volume was assessed at three time intervals before (−30, −15, 0 min) and at 5, 10, 20, 30, 40, 50, 60, 80, 100 and 120 min after stimulation by means of ultrasonography. CCK and PP plasma levels were determined at each time interval.Exocrine pancreatic function was assessed using the pancreolauryl serum test (PLT). Six patients with CP had severe exocrine pancreatic insufficiency (EPI) (PLT<1.8 μg/ml) with steatorrhea, eight patients had mild-moderate EPI. Fasting gallbladder volume was increased in CP (32.3±3.1 cm3) as compared to controls (20.5±1.2 cm3) (P<0.01). Peak gallbladder contraction (percent of initial volume) in CP ranged from 5 to 55% (controls: 8–46%) following ceruletide and from 17 to 86% (controls: 27–80%) following the test meal (NS). There was no correlation between the degree of EPI according to PLT and peak gallbladder contraction. Gallbladder emptying in CP patients was not different from controls, although the postprandial CCK response was significantly impaired (P<0.01). Postprandial PP response in CP was correlated with the PLT result (r=0.78;P<0.01) but not with gallbladder emptying or refilling time. We conclude that gallbladder emptying and refilling following the oral administration of a test meal or the stimulation with a pharmacological dose of ceruletide is normal in patients with chronic pancreatitis. Postprandial gallbladder emptying is not influenced by the degree of exocrine pancreatic insufficiency.

Relationship of Sliding Hiatus Hernia to Gastroesophageal Reflux Disease: A Possible Role for Helicobacter pylori Infection?

Sliding hiatal hernia is a common endoscopic finding with a prevalence that increases with the age of patients. Although nearly all patients with GERD have HH, only a minority of patients with hernia reports reflux symptoms. Our hypothesis is that H. pylori infection may be responsible for the high number of asymptomatic hernias. After exclusion of patients with peptic ulcer, 507 patients with an endoscopic diagnosis of hernia were considered. Patients were divided into three groups: A, ≤45 years, 141 patients; B, 46–60 years, 144 patients; and C, ≥61 years, 222 patients. Presence of reflux symptoms (questionnaire) and esophagitis, H. pylori status, and gastric histology were recorded. The prevalence of hernia in the total series was 11% in group A, 23% in B, and 38% in C. Aging was associated with a significant increase in H. pylori prevalence and corpus gastritis scores, and a parallel decrease of GERD symptom prevalence, which was 66.6% in group A, 52.1% in B, and 46.8% in C (P < 0.01). Taking the three groups together, prevalence of H. pylori infection was higher in patients without GERD than with GERD (66.4 vs 57.3%, P < 0.05), and higher in patients with nonerosive GERD than erosive GERD (62.8 vs 48.6%, P = 0.02); corpus gastritis scores were significantly higher in patients without GERD than those with GERD and in those with nonerosive than erosive GERD. In conclusion, H. pylori infection protects against development of GERD in subjects with hiatus hernia. This effect is significantly more evident in the elderly where, in spite of the high prevalence of hernia, only a small number of individuals develop GERD. The development of a corpus-predominant gastritis is probably responsible for this effect.

Impaired interdigestive pancreatic polypeptide release. Early hormonal disorder in chronic pancreatitis

The purpose of this study was to investigate interdigestive cycling and postprandial release of pancreatic polypeptide (PP) in relation to exocrine pancreatic function in chronic pancreatitis (CP). We investigated nine patients with mild-moderate CP (MCP), eight patients with severe CP and steathorrea (SCP), and 17 healthy subjects as controls. Interdigestive antroduodenal motility was monitored by means of manometry. Following two consecutive motility cycles, a standard test meal was administered. Plasma samples were drawn for PP determinations every 15 min throughout the entire study, which concluded 2 hr after ingestion of the meal. Mean interdigestive PP plasma concentrations during phase III motor activity were lower in MCP (146±46 pg/ml) than in controls (270±42 pg/ml) and lower still in SCP (55±8 pg/ml). Accordingly, the percent increase in PP concentrations during phase III over those in phase I was progressively decreased from controls (112%) to MCP (62%) to SCP (19%). Mean interdigestive PP concentrations were also lower during phase I and II in SCP than in controls or MCP. None of the postprandial parameters for PP release was affected in the early stage of disease, while mean, peak, and integrated postprandial values were significantly lower in SCP than in controls or MCP. Thus, we observed a progressive diminution of both interdigestive and postprandial PP release with increasing severity of disease. Interdigestive release parameters, in particular, were tightly correlated with exocrine function. CP appears to alter interdigestive PP release to a greater extent than postprandial PP release; this effect is already apparent in early stages of the disease. Impaired release of PP during phase III motor activity may represent an early hormonal disorder in CP.