Abstract: OBJECTIVE: The mechanisms underlying symptoms in gastro-oesophageal reflux disease, particularly in non-erosive reflux disease (NERD), remain to be fully elucidated. Weakly acidic reflux and the presence of gas in the refluxate could be relevant in the pathogenesis of symptoms. METHODS: To assess the relationship between symptoms and weakly acidic, acid and mixed (liquid-gas) reflux, 24 h oesophageal pH-impedance monitoring was performed in 32 NERD and in 20 oesophagitis patients. In 12 NERD patients the study was repeated following 4 weeks treatment with a proton pump inhibitor (PPI). Impedance-pH data were compared with those of 10 asymptomatic controls. Heartburn and acid regurgitation were considered in the analysis of symptoms. RESULTS: 15 NERD patients showed a physiological acid exposure time (pH-negative). Weakly acidic reflux was significantly less frequent in patients (25% (2%), mean (SE)) than in controls (54% (4%), p<0.01). Gas was present in 45-55% of reflux events in patient groups and controls, and decreased following PPI treatment. In NERD pH-negative patients, weakly acidic reflux accounted for 32% (10%) (vs 22% (6%) in NERD pH-positive and 12% (8%) in oesophagitis patients) and mixed reflux for more than two-thirds of all symptom-related refluxes. Multivariate logistic analysis showed that in NERD pH-negative patients, the risk of reflux perception was significantly higher when gas was present in the refluxate (odds ratio, 3.2; 95% CI, 1.2 to 10; p<0.01). CONCLUSIONS: The large majority of symptoms, in all patients, are related to acid reflux. In NERD patients, the presence of gas in the refluxate significantly enhances the probability of reflux perception. These patients are also more sensitive to less acidic reflux than oesophagitis patients.
Abstract: Chronic intestinal pseudo-obstruction represents a cause of persistent functional intestinal failure either "secondary" to specific conditions or "chronic intestinal idiopathic pseudo-obstruction" in origin. The diagnosis is mainly clinical, supported by radiological and/or endoscopic findings excluding any mechanical cause of intestinal obstruction. We reported a case of a 39-year-old woman with chronic intestinal idiopathic pseudo-obstruction, who underwent colectomy with ileorectal anastomosis; histological examination of the surgical specimen did not reveal myogenic or neurogenic defects or other pathological abnormalities indicative of an underlying neuromuscular impairment. Because of the apparent integrity of the gut neuromuscular layer, we tested whether a functional impairment affected colonic single smooth muscle cells. Muscle cells were isolated from the right colon and their contractile response to a receptor-dependent agonist evaluated in comparison to that obtained from controls. The cell contraction induced by acetylcholine in a dose response manner was markedly decreased in the patient affected by chronic intestinal idiopathic pseudo-obstruction compared with cells from controls (percentage of cell shortening with maximal dose of acetylcholine [10(-6)M]: 10.7+/-3% versus 34.2+/-4%, respectively). The present findings indicate a specific defect of colonic smooth muscle cells likely related to an ineffective response to acetylcholine.
Abstract: AIM: To prospectively investigate a new high resolution MRI technique for dynamic evaluation of the enhancement kinetics of bowel parietal layers and to correlate it with CDAI, CRP, endoscopic activity and histologic features. METHODS: About 16 consecutive patients with proven diagnosis of CD underwent ileocolonoscopy with biopsy and serial bowel dynamic contrasted-MRI (D-CE-MRI) evaluated in blind fashion. Quantitative analysis of bowel wall enhancement kinetics was performed basing on signal to noise ratio (SNR) of inner parietal layers (Mucosa-Submucosa, M-SM) and outer parietal layers (Muscular-Serosa, Ms-S). Disease activity was defined by CDAI > 150, serum CRP > 5 mg/dL and histologic results. RESULTS: About 9 patients showed a layered enhancement of bowel wall (8 active, 1 inactive), whereas inactive (7 cases) group presented a homogeneous pattern. In active patients we found a significant difference in parietal layered enhancement curves (M-SM vs. Ms-S, P < 0.03) not observed in inactive disease and controls (intra-group analysis). M-SM and Ms-S enhanced curves in clinically active patients were significantly different respect to those of patients with inactive CD (P < 0.001) (inter-group analysis). Parietal D-CE-MRI pattern well correlated with histologic features (r = 0.8; P < 0.001, Spearman test). CONCLUSIONS: D-CE-MRI can be a useful tool for clinical follow-up and in the treatment strategies in CD patients.
Abstract: Proximal oesophageal acid reflux is increased in gastro-oesophageal reflux disease (GORD) patients with oesophageal and extra-oesophageal symptoms, the latter particularly in presence of oesophagitis. This study was aimed to assess the proximal extent of reflux, both acid and weakly acidic, in GORD patients with and without oesophagitis and to characterize, using an animal model of GORD, the relationship between acute oesophagitis and proximal extent of reflux. Proximal extent of reflux was evaluated during 24-h pH-impedance monitoring in 17 oesophagitis, 27 non-erosive reflux disease (NERD) patients and 10 asymptomatic controls. In five adult cats, reflux events were simulated by intra-oesophageal retrograde injection of a radiopaque solution. Proximal extent of simulated reflux was fluoroscopically assessed before and after inducing acute oesophagitis. The percentage of proximal reflux was 11% in controls, 22% in NERD and 38% in oesophagitis patients (P < 0.05 vs NERD). Weakly acidic reflux showed higher proximal extent in oesophagitis than in NERD patients but it was less proximally propagated than acid reflux. In cats, proximal reflux was significantly increased during acute oesophagitis. Oesophagitis patients show higher proximal extent of reflux, acid and weakly acidic, when compared with NERD patients and controls. In the experimental model, acute oesophagitis favours proximal migration of simulated reflux.
Abstract: OBJECTIVE: To examine the mechanisms of action of ursodeoxycholic acid (UDCA) on gallbladder (GB) muscle cells in patients with symptomatic cholesterol gallstones (GSs) as it reduces the incidence of acute cholecystitis. Design and PATIENTS: A double-blind study was performed on 15 patients, 7 randomised to UDCA and 8 to placebo, treated for 4 weeks before cholecystectomy. Muscle contraction induced by cholecystokinin (CCK)-8, acetylcholine (ACh) and potassium chloride (KCl) was determined in enzymatically isolated GB muscle cells, and cholesterol levels were determined in plasma membranes. H(2)O(2), lipid peroxidation, platelet-activating factor (PAF)-like lipids, prostaglandin E(2) (PGE(2)) and catalase activity were determined as biochemical markers of oxidative stress and inflammation in muscle cells. RESULTS: UDCA significantly increased GB muscle cell contraction induced by all concentrations of CCK-8, ACh and KCl, and reduced the plasma membrane cholesterol (mean (SD) 0.32 (0.16) vs 0.72 (0.5) micromol/mg of protein) compared with placebo. In GB muscle cells, UDCA treatment significantly decreased the levels of H(2)O(2) (4.4 (1.9) vs 13.7 (5.3) micromol/mg of protein), lipid peroxidation (malondialdehyde levels 1.3 (0.4) vs 2.52 (0.7) nmol/100 mg of protein), PAF-like lipids (8.9 (4.9) vs 29.6 (7.1) pg/mg of protein) as well as the production of PGE(2) (142 (47) vs 365 (125) pg/mg of protein) and catalase activity (14.5 (9.4) vs 35.8 (12.7) units/mg of protein) when compared with placebo. CONCLUSION: These studies suggest that UDCA treatment improves GB muscle contractility by decreasing the cholesterol content in the plasma membrane of muscle cells, and the biochemical parameters of oxidative stress, thus explaining its possible therapeutic mechanisms in patients with symptoms of cholesterol GSs.
Abstract: BACKGROUND: Acid exposure of proximal oesophagus and dilated intercellular space diameters of oesophageal epithelium are relevant in the perception of gastro-oesophageal reflux. AIM: To explain the relationship between gastro-oesophageal reflux disease symptoms, acid exposure and intercellular space diameter along the oesophageal epithelium and to assess time-related variability of intercellular space diameter. METHODS: Thirty-three non-erosive reflux disease (NERD), six erosive oesophagitis patients and 12 asymptomatic controls underwent oesophageal manometry and 24-h dual-channel oesophageal pH-monitoring following endoscopy. Biopsies were taken 5 cm above the LES and 10 cm below the UES, at comparable levels, as pH sensors. A total of 100 intercellular space diameters per patient/control were measured blindly at transmission electron microscopy. In 15 patients, the investigation was repeated after 1 year. RESULTS: In all NERD patients, acid exposure was higher at mid-proximal oesophagus (P < 0.01) and mean intercellular space diameters, at distal and mid-proximal oesophagus, was three- and twofold higher (1.5 and 0.82 micro m, respectively) compared with controls. Intra-patient intercellular space diameter values were stable over time, not overlapping with those of controls. CONCLUSIONS: Dilation of intercellular space diameter occurs along the distal and proximal oesophageal epithelium in NERD patients and could be responsible for the enhanced perception of proximal acid reflux. This finding appears to be time-reproducible and to represent a sensitive, histopathological marker of NERD.
Abstract: AIM: To evaluate the safety and efficacy of a long-term therapy with infliximab in Crohn's disease (CD) and ulcerative colitis (UC) patients retrospectively. METHODS: The medical charts of 50 patients (40 CD and 10 UC), who received after a loading dose of 3 infliximab infusions scheduled re-treatments every 8 wk as a maintenance protocol, were reviewed. RESULTS: Median (range) duration of treatment was 27 (4-64) mo in CD patients and 24.5 (6-46) mo in UC patients. Overall, 32 (80%) CD and 9 (90%) UC patients showed a sustained clinical response or remission throughout the maintenance period. Three CD patients shortened the interval between infusions. Eight (20%) CD patients and 1 UC patient underwent surgery for flare up of disease. Nine out of 29 CD and 4 out of 9 UC patients, who discontinued infliximab scheduled treatment, are still relapse-free after a median of 16 (5-30) and 6.5 (4-16) mo following the last infusion, respectively. Ten CD patients (25%) and 1 UC patient required concomitant steroid therapy during maintenance period, compared to 30 (75%) and 9 (90%) patients at enrollment. Of the 50 patients, 16 (32%) experienced at least 1 adverse event and 3 patients (6%) were diagnosed with cancer during maintenance treatment. CONCLUSION: Scheduled infliximab strategy is effective in maintaining long-term clinical remission both in CD and UC and determines a marked steroid sparing effect. Long-lasting remission was observed following infliximab withdrawal.
Abstract: BACKGROUND: Proximal acid reflux is common in gastro-oesophageal reflux disease and is a determinant of symptoms. Patients with hiatal hernia complain of more symptoms than those without and are less responsive to proton-pump inhibitors. AIM: To evaluate the role of hiatal hernia on spatiotemporal characteristics of acid reflux. METHODS: Thirty seven consecutive gastro-oesophageal reflux disease patients underwent endoscopy, videofluoroscopy, manometry and multichannel 24-h pH test. Data were compared with those of 15 asymptomatic controls. Multivariate linear regression was used for statistical analysis. RESULTS: At videofluoroscopy, hiatal hernia was found in 16 of 37 patients. The mean size of hiatal hernia was 3.4 cm. Patients showed significantly prolonged acid clearance time, both at proximal and distal oesophagus, compared with controls. Hiatal hernia patients showed a significantly delayed acid clearance, along the oesophageal body, compared with non-hiatal hernia patients. The prolonged acid exposure was maintained during upright and supine position. The presence of hiatal hernia significantly predicted acid clearance delay in the distal and proximal oesophagus [at 10 cm below upper oesophageal sphincter: Delta + 2.5 min (95% confidence interval: 0.4-4.5); P < 0.02]. CONCLUSIONS: The presence of hiatal hernia is a strong predictor of more prolonged proximal oesophageal acid exposure and clearance. Hiatal hernia is likely to play a role in the pathophysiology of gastro-oesophageal reflux disease symptoms, and should be taken into greater consideration in the treatment strategies of the disease.
Abstract: Control of the G1/S-phase transition as well as angiogenic switch are two of the most studied mechanisms in cancer. The current study examined the correlation between the immunohistochemical expression of pRb2/p130, VEGF, EZH2, p53, p16, p21waf-1, p27, and PCNA in Barrett's esophagus (BE). Overall, p53 showed a much higher expression in BE patients (up to 50%) than in controls (1-10%) (P < 0.005). Also p21 showed a downregulation in BE when compared to normal esophagus (70% of cells vs. 65%), but the difference did not show any statistical significance (P = 0.45). pRb2/p130 was detected in 80% of cells in normal controls, but showed positive in only 20% of cells in BE biopsies. Additionally, Rb2/p130 expression was inversely correlated to that of VEGF, EZH2, and PCNA (P < 0.0001, P = 0.0032, P < 0.001, respectively). p27 stained more intensely and in a widespread manner (70%) cells in normal esophageal tissues but about only 30% in BE samples (P < 0.001). Lastly, in accordance with other reports, we also found p16 expressed by immunohistochemistry at high levels in normal controls and at low levels in BE (P < 0.001). In conclusion, p16, p21, p27, and p53 staining confirmed previously published data. Interestingly, pRb2/p130 expression was found significantly decreased in metaplastic epithelium compared to normal controls and showed significant inverse correlation with the expression of other markers, such as VEGF, EZH2, and PCNA. These data, taken together, indicate that these molecular events occurring in Barrett's metaplasia (BM) may represent one of the many steps taking place during esophageal malignant progression such as impairment of cell-cycle control, altered differentiation, and unbalanced angiogenesis.
Abstract: BACKGROUND: Increasing evidence shows that inflammation plays a major role in the aetiology of catabolism and wasting observed in inflammatory bowel disease via growth hormone resistance. AIM: To evaluate the effect of infliximab treatment on the growth hormone/insulin-like growth factor-1 axis. METHODS: Fourteen adults with active Crohn's disease or ulcerative colitis underwent three infliximab infusions at a dose of 5 mg/kg for induction of remission, plus two maintenance infusions 8 weeks apart. Blood samples were collected for the analysis of serum growth hormone, insulin-like growth factor-1, insulin-like growth factor-binding protein-3 and acid labile subunit. RESULTS: Serum insulin-like growth factor-1 and insulin-like growth factor-binding protein-3 concentrations, which were significantly lower in inflammatory bowel disease patients before treatment compared with controls (P < 0.01), significantly increased during the induction phase (+58% and +29%, respectively, after the second infusion, P < 0.01), and dropped to baseline levels during maintenance therapy. Both insulin-like growth factor-1 and insulin-like growth factor-binding protein-3 showed significant negative correlations with C-reactive protein (rho = -0.37, P = 0.002; rho = -0.35, P = 0.01, respectively). Growth hormone and acid labile subunit levels were not statistically different between controls and inflammatory bowel disease patients either at baseline or during treatment. CONCLUSIONS: Infliximab induction treatment reverses growth hormone resistance observed in active inflammatory bowel disease through the suppression of systemic inflammation. The restored growth hormone/insulin-like growth factor-1 axis is impaired again following the prolonged interval between maintenance infusions, possibly because of the subclinical reactivation of the inflammatory process.
Abstract: Ursodeoxycholic acid (UDCA) prevents in vitro gallbladder (GB) muscle damage caused by acute cholecystitis and reduces risk of biliary pain and complications in gallstone (GS) patients. These effects could be partially explained by the improved GB bile turnover. OBJECTIVES: To assess the effect of short-term UDCA treatment on GB motility and bile turnover. METHODS: Ultrasonographic (US) assessment of GB volumes was performed in 16 GS patients, in the postprandial phase, for 90 min with a time sampling of 1 min, before and after 30 days of UDCA (10 mg kg(-1) die(-1)) or placebo, randomly assigned. US data were analysed with statistical tools and with computer fluido-dynamic (CFD) software Fluent(TM) to simulate GB bile flow. RESULTS: After therapy, fasting volume (FV) increased from 21.6 +/- 9 to 28.2 +/- 12 mL (p < 0.001) while the ejection fraction (EF) remained unchanged (44.5 +/- 17% vs 45.1 +/- 20%; p: ns). Volumes before and after treatment were poorly correlated (0.02 < r < 0.35), unlike those in placebo patients (r > 0.6). The average GB volume was increased in 7 out of 10 patients following UDCA (range 7-67%). CFD analysis supports the finding of improved bile flow after treatment. CONCLUSIONS: Unlike results of conventional US parameters of GB motility, CFD analysis shows that UDCA improves GB bile turnover in GS patients.
Abstract: OBJECTIVES: It has been demonstrated that dilation of intercellular spaces of esophageal epithelium is a marker of tissue injury in GERD patients with a pathological esophageal acid exposure time. To evaluate the relationship among ultrastructural changes, acid esophageal exposure, and GERD symptoms, intercellular space diameters have been assessed in nonerosive reflux disease (NERD) patients with/without abnormal acid exposure time. METHODS: Following a pharmacological wash-out, 20 NERD patients underwent upper endoscopy, esophageal manometry, and 24-h pH monitoring. Biopsies were taken at 5 cm above the lower esophageal sphincter and intercellular space diameters were measured on transmission electron microscopy photomicrographs. Seven asymptomatic controls underwent the same protocol. RESULTS: Acid exposure time was in the normal range in all controls and in 11 patients (NERD pH-negative); it was abnormal in 9 patients (NERD pH-positive). Mean intercellular space diameter in NERD pH-negative and in NERD pH-positive patients was three times greater than in controls (1.45 and 1.49 microm vs 0.45, p < 0.001). Mean values of maximum intercellular spaces in all NERD patients were greater, two-fold or more, than those in controls (p < 0.001). No difference in mean and maximal space diameters was observed between NERD pH-positive and pH-negative patients. CONCLUSIONS: Dilation of intercellular spaces is a feature of NERD patients, irrespective of esophageal acid exposure, and can be considered an objective, structural marker of GERD symptoms. Impaired esophageal mucosal resistance, even to small amounts of acid refluxate, plays a key role in the pathophysiology of NERD.
Abstract: BACKGROUND AND AIMS: Improvements in symptoms following endoscopic procedures for gastro-oesophageal reflux disease (GORD) are seldom supported by normalisation of acid exposure time at the distal oesophagus. However, the distribution of gastric acid within the proximal oesophagus is a main determinant of symptom generation in GORD patients. In this study, our aim was to assess the effect of endoscopic insertion of hydrogel expandable prostheses into the oesophageal submucosa on spatiotemporal characteristics of gastro-oesophageal reflux. METHODS: Oesophageal manometry and multichannel ambulatory 24 hour pH monitoring were carried out in nine patients before and six months after the endoscopic procedure. Dynamic characteristics of gastro-oesophageal reflux in patients were also compared with those in 13 asymptomatic controls. RESULTS: Acid exposure time (AET) at the distal oesophagus decreased from 11.7% (95% confidence interval 6.1-21.8) at baseline to 7.7% (3.7-11.6) at follow up (NS). Of the nine patients, distal AET normalised in three. AET at the middle (7.6% (2.9-12.3)) and proximal (2.4% (0.1-4.8)) oesophagus decreased significantly in all patients (2.4% (0.3-4.5), p <0.01; 1.2% (0.2-2.2), p<0.05 respectively). Proximal extent of acid events significantly decreased in all patients at follow up (37.3% v 9.5%), reaching values observed in asymptomatic controls. Median GORD health related quality of life scores significantly improved from 35.5 at baseline to 9.4. CONCLUSIONS: Despite the lack of a significant improvement in traditional pH variables, endoscopic implant of hydrogel prostheses above the lower oesophageal sphincter significantly decreases proximal spread of acid reflux into oesophageal body. This effect would explain the improvement in symptoms in patients six months after therapy.
Abstract: BACKGROUND: The majority of patients with gastro-oesophageal reflux disease do not present with erosive oesophagitis and make up a heterogeneous group. Patients with non-erosive gastro-oesophageal reflux disease are less responsive than patients with oesophagitis to acid-suppressive therapy. AIM: To assess the role of acid reflux in gastro-oesophageal reflux disease symptoms. METHODS: The spatio-temporal characteristics of reflux events were analysed and related to reflux perception in 45 patients with non-erosive gastro-oesophageal reflux disease and 20 patients with erosive oesophagitis. RESULTS: Compared with healthy controls, all patients showed a higher intra-oesophageal proximal spread of acid, which was prominent in patients with non-erosive gastro-oesophageal reflux disease (> 50% of events lasting for 1-2 min). Irrespective of mucosal injury, the risk of reflux perception was very high when acid reached proximal sensors (odds ratio, 7.6; 95% confidence interval, 4.6-12.5), being maximal in patients with non-erosive gastro-oesophageal reflux disease with normal acid exposure time (odds ratio, 11; 95% confidence interval, 5.2-22.3). CONCLUSIONS: Patients with non-erosive gastro-oesophageal reflux disease are characterized by a significantly higher proportion of proximal acid refluxes and a higher sensitivity to short-lasting refluxes when compared with patients with oesophagitis. The highest proximal acid exposure and highest perception occurred in patients with non-erosive gastro-oesophageal reflux disease presenting with a normal pH-metric profile. The assessment of acid distribution and its perception in the oesophageal body can better identify reflux patients who should benefit from acid-suppressive treatment.
Abstract: BACKGROUND: GERD is the most frequent disorder of the esophagus. Endoscopic minimally invasive treatment is desirable. However, the results of injection techniques have been disappointing. METHODS: A pilot study was conducted in patients with GERD, who required continuous therapy with a proton pump inhibitor, in which ethylene-vinyl-alcohol was injected into the muscle of the gastric cardia. Primary endpoints were the safety of the procedure, the effect on lower esophageal sphincter pressure and the stability of the injected material. A secondary endpoint was the effect on heartburn score after discontinuation of treatment with a proton pump inhibitor. RESULTS: Ethylene-vinyl-alcohol injection into the cardia resulted in circular diffusion of the product in 10 of 15 cases, suggesting that implantation into the muscle is feasible. Lower esophageal sphincter pressure was increased in 13 of 15 cases at 1 month and was sustained at a median follow-up of 6 months (range 4-12 months). Mean plus minus SEM of lower esophageal sphincter pressures (15 patients) were 12.2 plus minus 0.9, 18.7 plus minus 1.5 (p = 0.001 at baseline), and 16.7 plus minus 1.3 mm Hg (p = 0.038 from baseline) at, respectively, baseline, 1 month follow-up, and final follow-up. There was also a sustained reduction in heartburn score (off proton pump inhibitor) (3.40 plus minus 0.13 vs. 1.53 plus minus 0.24 and 1.87 plus minus 0.26 at baseline vs. 1 month and final follow-up, respectively; p < 0.01). Nine of the 15 patients had more than 50% of the injected material in place at second follow-up (at 6 months for 8 patients; at 12 months for 1 patient). In only 2 patients was there loss of more than 75% of injected ethylene-vinyl-alcohol. Persistence of greater than 50% of the material was associated with achievement of a circular injection. Only 4 patients had to resume therapy with a proton pump inhibitor. Mild retrosternal discomfort was observed in 8 patients; this disappeared in all cases after a maximum of 3 days. CONCLUSIONS: Ethylene-vinyl-alcohol implantation in the muscle of the cardia is feasible and safe. It leads to a sustained increase in resting lower esophageal sphincter pressure. This is associated with a sustained improvement in heartburn score for patients who previously required continuous therapy with a proton pump inhibitor.
Abstract: BACKGROUND: Sphincter of Oddi dysfunction is diagnosed at manometry and, after cholecystectomy, non-invasively at quantitative choledochoscintigraphy. Patients may benefit from endoscopic sphincterotomy. AIMS: The aim of this study was to assess the usefulness of choledochoscintigraphy compared with manometry in predicting outcome of sphincterotomy in post cholecystectomy patients with sphincter of Oddi dysfunction. PATIENTS AND METHODS: Thirty patients with biliary-type pain complying with the Rome diagnostic criteria of sphincter of Oddi dysfunction and belonging to biliary group I and II were subjected to clinical evaluation, choledochoscintigraphic assessment of the hepatic hilum-duodenum transit time, endoscopic retrograde cholangiopancreatography, and perendoscopic manometry. Twenty two biliary group I and II patients with prolonged hepatic hilum-duodenum transit times were invited to undergo sphincterotomy. Fourteen patients underwent sphincterotomy; eight refused. Clinical and scintigraphic assessments were performed at follow up. RESULTS: Hepatic hilum-duodenum transit time was delayed in all patients with manometric evidence of sphincter of Oddi dysfunction, in all biliary group I patients and in 64% of biliary group II patients. At follow up, all patients who underwent sphincterotomy were symptom free and hepatic hilum-duodenum transit time had either normalised or significantly improved. A favourable post sphincterotomy outcome was predicted in 93% of cases at choledochoscintigraphy and in 57% at manometry. CONCLUSIONS: Quantitative choledochoscintigraphy is a useful and non-invasive test to diagnose sphincter of Oddi dysfunction as well as a reliable predictor of sphincterotomy outcome in post cholecystectomy biliary group I and II patients, irrespective of clinical classification and manometric findings.
Abstract: Impaired gallbladder motility may contribute to gallstone pathogenesis by providing time for nucleation and aggregation of cholesterol crystals. Simultaneous scintigraphic-ultrasonographic techniques have been proposed to assess alternating phases of gallbladder emptying and filling. To evaluate patterns of gallbladder motility and of postprandial bile flow by means of a single ultrasonographic technique, 12 healthy volunteers and 20 gallstone patients underwent minute-by-minute gallbladder ultrasonography for 3 h postprandially. Mathematical analysis of volume measurements was used to estimate hepatic and cholecystic bile flux through the gallbladder. Compared to controls, gallstone patients showed greater amounts of unexchanged cholecystic-to-hepatic bile (11% vs. 1%, p <.001) and most of them showed impaired gallbladder washout efficacy. Utrasonographic values of bile exchanges were similar to those derived from scintigraphic-sonographic studies in comparable groups of subjects. This study provides new ultrasonographic variables, which better express gallbladder bile retention in gallstone patients and strongly discriminate gallstone patients from controls.
Abstract: BACKGROUND AND AIMS: Even if the motor activity of the gall bladder and sphincter of Oddi (SO) are integrated, it is not known if the presence of stones in the gall bladder affects SO function. The aim of the study was to compare SO motor activity in patients with and without gall stones. PATIENTS AND METHODS: In a series of 155 patients consecutively submitted to endoscopic retrograde cholangiopancreatography and SO manometry for suspected biliary or pancreatic disease, 23 gall stone patients had recurrent episodes of biliary or pancreatic pain (colicky group); 52 patients had non-biliary/pancreatic-type abdominal pain/discomfort, and of these, 15 had gall stones (non-colicky group), 25 were free of stones (controls), and 12 had undergone cholecystectomy. RESULTS: SO basal pressure in gall stone patients in the colicky or non-colicky group was significantly higher than in controls (p<0.001). SO basal pressure recorded in postcholecystectomy patients did not differ from controls. SO phasic activity did not differ between the patient groups. SO dysfunction was detected in more than 40% of gall stone patients irrespective of associated biliary/pancreatic pain but in none of the control subjects (p<0.001). CONCLUSIONS: Gall stones are frequently associated with increased SO tone which may obstruct bile flow thus acting to facilitate gall bladder stasis, and may play a role as a cofactor in biliary/pancreatic pain.
Abstract: OBJECTIVE: The present study aimed to evaluate the patterns of antral contractility and pylorus opening and closure in relation to transpyloric flow of a nutrient liquid meal. METHODS: Ultrasound images of the antro-pyloro-duodenal tract were continuously tape-recorded in healthy volunteers for 1 h postprandially and were reviewed twice later by independent observers. Episodes and patterns of pylorus opening and closure, antral-wall contractions, and transpyloric flow were assessed separately and their time relations were identified. RESULTS: Transpyloric flow (forward, 56%+/-13%; retrograde, 19%+/-11%; and to and fro, 25%+/-14%) occurred essentially during episodes of prolonged pylorus opening not associated with occlusive antral or duodenal proximal contraction, which represented the antro-pyloro-duodenal common chamber. The antro-pyloro-duodenal common chamber lasted on average 36+/-12 s and represented 41%+/-12% of the total observation period. Different patterns of antral contractions were identified according to whether they reached or occluded the terminal antrum and pylorus. Preterminal antral contractions (46%+/-12%) did not propagate beyond the proximal two thirds of the antrum. Terminal antral contractions (54%+/-12%) propagated along the entire antrum and could either occlude (20%+/-9%) or not occlude (42%+/-17%) the lumen. Pyloric opening independent of antral contractions and related to nonocclusive antral contractions could occur equally at the onset of the antro-pyloro-duodenal common chamber. Pyloric closure independent of antral contractions put an end to transpyloric flow in 73%+/-6% of the antro-pyloro-duodenal common chamber. CONCLUSIONS: The final passage of contents from the stomach to the duodenum after the ingestion of a caloric liquid meal is the result of one or more episodes of uni- or bi-directional transpyloric flow, which are regulated by several motor events. The contractile states of the antrum and pylorus show specific features that variably interrelate to provide mixing and to regulate the transpyloric flow of ingesta. A crucial regulator of transpyloric flow appears to be the spatio-temporal relation between antral contractions and pyloric closure rather than the contractile events per se. An equal number of pyloric openings related, and unrelated, to antral contractions appears to determine the onset of the antro-pyloro-duodenal common chamber and, thus, of transpyloric flow. Pyloric closure unrelated to antral contractions appears to be the main mechanism that interrupts transpyloric flow. In conclusion, it appears that the antro-pyloro-duodenal tract acts as a functional unit in the digestion of a liquid caloric meal.
Abstract: The postprandial release of cholecystokinin (CCK) regulates gallbladder (GB) contraction but little is known about the role, if any, of the still-elevated CCK blood levels on subsequent GB refilling. To assess the role of CCK in GB refilling, a CCK-receptor antagonist, loxiglumide, or saline were infused intravenously in a random double-blind fashion after the ingestion of a liquid test meal in 16 healthy subjects. An identical study protocol was performed in 10 GB "contractor" patient with radiolucent stones to ascertain whether the reported reduced CCK effect on GB emptying also affects GB refilling. GB volumes were assessed ultrasonographically in the fasting state and for 150 min at 15-min intervals after meal ingestion. GB volumes during postprandial refilling were significantly greater during loxiglumide than placebo infusion (P < 0.01), but they did not differ between gallstone and control subjects. In conclusion, postprandial endogenous CCK has a relevant role in delaying GB refilling, and this effect is not altered in patients with radiolucent gallstones.
Abstract: BACKGROUND: Impaired gallbladder emptying is a pathogenetic factor in gallstone formation. To test whether gallbladder motility can be improved by high-dose cholecystokinin (CCK), gallbladder emptying was measured sonographically in 21 patients with cholesterol gallstone disease and 6 healthy controls. METHODS: The effects of CCK infusions of 0.06 IDU/kg.min (group A, n = 11) and 0.12 IDU/kg.min (group B, n = 10) were compared with the response to a standard CCK infusion (0.02 IDU/kg.min). Controls received CCK at all infusion rates. RESULTS: The ejection fraction was smaller after CCK infusion of 0.06 IDU/kg.min than after the standard stimulus (group A, 52 +/- 10 versus 64 +/- 10%, p < 0.05; controls, 66 +/- 10 versus 91 +/- 3%, p < 0.05). After infusion of 0.12 IDU/kg.min CCK ejection fractions decreased even more (group B, 44 +/- 16 versus 65 +/- 12%, p < 0.05; controls, 54 +/- 12 versus 91 +/- 3%, p < 0.05). High-dose CCK infusions shortened the ejection period markedly, whereas the ejection rate remained unaltered. CONCLUSIONS: High-dose CCK does not improve gallbladder motility but blocks the ejection process early, leading to reduced gallbladder emptying in gallstone patients and healthy subjects.
Abstract: The hepatic hilum-duodenum transit time (HHDT) was evaluated in cholecystectomized subjects to assess its relationship with the motor function of the sphincter of Oddi (SO) and its diagnostic accuracy in the detection of SO dysfunction. The study was performed in asymptomatic controls and symptomatic patients with SO dysfunction before and after sphincterotomy. HHDT showed a direct correlation with manometric SO maximal basal pressure (r = 0.77; P < 0.001) but not with SO phasic activity. In sphincterotomized subjects HHDT did not differ from that of the asymptomatic subjects, and HHDT, which was prolonged before sphincterotomy, normalized after sphincterotomy. HHDT had a 100% specificity and an 83% sensitivity in diagnosing SO dysfunction when compared to SO manometry. In conclusion, the cholescintigraphic HHDT is mainly related to the SO maximal basal pressure, presenting an elevated specificity and a satisfactory sensitivity in the diagnosis of SO dysfunction in cholecystectomized subjects.
Abstract: To evaluate whether the extent of postprandial gall bladder emptying is correlated with gall bladder fasting volume, gall bladder motility was studied in 56 patients with cholesterol gall stone and 19 control patients. Gall bladder volumes were determined sonographically, while cholecystokinin plasma values were measured radioimmunologically. Twenty three per cent of gall stone patients were classified as pathological contractors (residual fraction > mean +2SD of controls) and 77% as normal contractors. Normal but not pathological contractor patients exhibited larger gall bladder fasting volumes (mean (SEM)) (24.7 (1.7) ml) than controls (15.3 (1.2) ml, p < 0.001). In normal contractor patients and controls fasting volume was closely related with ejection volume (r = 0.97, p < 0.001) and residual volume (r = 0.80, p < 0.001). Although ejection volume was enlarged in normal contractor patients it did not compensate the increase in fasting volume. Thus, residual volumes were considerably increased not only in pathological contractors (12.7 (2.5) ml, p < 0.001) but also in normal contractor patients (7.0 (0.5) v 4.6 (0.6) ml, p < 0.001). Postprandial cholecystokinin secretion did not differ between patients and controls. It is concluded, that in normal contractor patients gall bladder fasting volume is closely correlated with ejection and residual volume. Thus, fasting volume may be an essential factor affecting postprandial gall bladder emptying. Large fasting volumes in cholesterol gall stone disease could thereby contribute to bile retention, which facilitates gall stone growth.
Abstract: Quantitative cholescintigraphy has been proposed as a noninvasive method to assess function of the sphincter of Oddi in cholecystectomized subjects. The present study evaluated several quantitative cholescintigraphic variables to assess their time-related variability as well as their capability to detect delay of choledochoduodenal bile flow. Cholescintigraphy with 2,6-diethylphenylcarbahoylmethyl diacetic acid 99mTc was performed in 24 cholecystectomized patients with recurrent biliary-like pain, laboratory evidence of bile stasis, normal hepatocellular function tests, and no evidence of choledocholithiasis. The study was also performed in 26 asymptomatic cholecystectomized subjects and repeated at 2-week intervals during identical experimental conditions in 10 of them. Of the following quantitative cholescintigraphic variables investigated, (a) hepatic T peak, (b) 50% hepatic retention (T peak, 1/2), (c) percent hepatic retention at 30 minutes, (d) percent hepatic retention at 40 minutes, (e) vein-hepatic hilum transit time, (f) vein-duodenum transit time, and (g) hepatic hilum-duodenum transit time, only the hepatic hilum-duodenum transit time showed a statistically significant correlation between the duplicate studies. Only vein-duodenum transit time and hepatic hilum-duodenum transit time discriminated the symptomatic from the asymptomatic patients; of the two variables, however, hepatic hilum-duodenum transit time showed less intrasubject variability and no overlap between the two groups of patients. Hepatic hilum-duodenum transit time showed a positive linear correlation with the maximum diameter of the choledochus. It is concluded that in cholecystectomized patients, the hepatic hilum-duodenum transit time appears to detect a delay of bile flow into the intestine better than any other cholescintigraphic variable. However, in patients with a dilated common bile duct, this variable cannot discriminate bile flow delay due to increased choledochal capacity and/or obstruction of the sphincter of Oddi.
Abstract: Bile is secreted continuously, although at various rates, from the liver into the biliary tree; whether bile is then diverted into the gallbladder or the duodenum depends on the relative resistance to flow mainly determined by the contractile state of the gallbladder and the choledochoduodenal junction. The resistance of the sphincter of Oddi is considered the principal factor in the regulation of the intracholedochal pressure and, therefore, of the common bile duct-gallbladder pressure gradient; however, filling of the gallbladder may also take place after total sphincterotomy. During late phase II of the interdigestive period intragallbladder pressure increments favour flow of a small amount of bile into the bile duct and, through the sphincter of Oddi, into the duodenum. During phase III of the interdigestive period maximal frequency of sphincter of Oddi phasic contractions blocks bile flow into the duodenum. After a meal tonic active contraction of the gallbladder causes an increase of the intraluminal pressure followed shortly by volume reduction of the viscus and outflow of bile accompanied by an intracholedochal pressure increment. Gallbladder hypotonia is a relevant factor in the pathogenesis of gallbladder stones. The gallbladder acts as a reservoir, since intracholedochal pressure is higher after than before cholecystectomy, and this may explain post-cholecystectomy choledochal dilatation and biliary pain by obstructed bile flow due to either stenosis or dyskinesia of the sphincter of Oddi.
