Residual Gallbladder Volumes Research Articles

Gastrointestinal defects in gallstone and cholecystectomized patients.

Several gallstone patients complain of dyspeptic symptoms, irrespective of the presence of typical colicky pain. Symptoms often persist after a cholecystectomy. Systematic studies on dyspepsia and dynamic gastrointestinal motor function are missing in gallstone patients with preserved gallbladder or after a cholecystectomy. Forty-six gallstone patients (age 55±2years; 15M, 31F) and 24 cholecystectomized patients (age 57±2years; 6M, 18F) (no difference in type and volume of gallstones between the two groups) were compared against a group of 65 healthy controls (age 51±2years; 30M, 35F). Dyspepsia occurring in the prior months was assessed by a questionnaire, gastric and gallbladder emptying by functional ultrasonography and orocecal transit time by a hydrogen breath test using a lactulose-enriched standard liquid meal. Gallstone patients had significantly greater dyspepsia, fasting and residual gallbladder volumes, and slower gallbladder emptying, gastric emptying and small intestinal transit time than controls. In cholecystectomized patients, gastric emptying further delayed, compared to gallstone patients and controls. Gallstone patients with the gallbladder "in situ" or after a cholecystectomy display dyspeptic symptoms. Symptoms are associated with multiple gastrointestinal motility defects involving the gallbladder, stomach and small intestine. After cholecystectomy, gastric emptying worsens.

The cholecystokinin-1 receptor antagonist devazepide increases cholesterol cholelithogenesis in mice.

A defect in gallbladder contraction function plays a key role in the pathogenesis of gallstones. The cholecystokinin-1 receptor (CCK-1R) antagonists have been extensively investigated for their therapeutic effects on gastrointestinal and metabolic diseases in animal studies and clinical trials. However, it is still unknown whether they have a potential effect on gallstone formation. To study whether the CCK-1R antagonists enhance cholelithogenesis, we investigated cholesterol crystallization, gallstone formation, hepatic lipid secretion, gallbladder emptying function and intestinal cholesterol absorption in male C57BL/6J mice treated by gavage with devazepide (4 mg/day/kg) or vehicle (as controls) twice per day and fed the lithogenic diet for 21 days. During 21 days of feeding, oral administration of devazepide significantly accelerated cholesterol crystallization and crystal growth to microlithiasis, with 40% of mice forming gallstones, whereas only agglomerated cholesterol monohydrate crystals were found in mice receiving vehicle. Compared to the vehicle group, fasting and postprandial residual gallbladder volumes in response to the high-fat meal were significantly larger in the devazepide group during cholelithogenesis, showing reduced gallbladder emptying and bile stasis. Moreover, devazepide significantly increased hepatic secretion of biliary cholesterol, but not phospholipids or bile salts. The percentage of intestinal cholesterol absorption was higher in devazepide-treated mice, increasing the bioavailability of chylomicron-derived cholesterol in the liver for biliary hypersecretion into bile. These abnormalities induced supersaturated bile and rapid cholesterol crystallization. The potent CCK-1R antagonist devazepide increases susceptibility to gallstone formation by impairing gallbladder emptying function, disrupting biliary cholesterol metabolism and enhancing intestinal cholesterol absorption in mice.

Ultrasonography analysis of gallbladder motility in patients with functional dyspepsia

BackgroundGallbladder motility has been studied in patients with functional gastrointestinal disorders, such as functional dyspepsia, irritable bowel syndrome and biliary disorders without gallstones and results of these observations are often inconclusive and conflicting. MethodsThe investigation was performed on 180 therapy-naïve newly diagnosed patients with functional dyspepsia (97 females and 83 males), aged 20–79 in which we have investigate ultrasonographically parameters of gallbladder motility. ResultsBonferroni post hoc correction stressed that fasting gallbladder volume and ejection fraction were significantly distorted in individuals with postprandial distress syndrome, although, the residual gallbladder volume was significantly lower in patients with epigastric pain syndrome comparing with other examinees. Ejection fraction of the gallbladder negatively correlated with body mass index. ConclusionThe impaired contractibility of the gall bladder in patients with functional dyspepsia, based on the results of this study, is illustrated by the changes in the ejection fraction, which was more pronounced in patients with the postprandial distress syndrome.

Gallbladder and gastric motility in obese newborns, pre‐adolescents and adults

Impaired gallbladder and gastric motility have been associated with obesity in adults. The timing of appearance of this dysfunction, however, is unclear. Lean and obese subjects from three different age groups were studied noninvasively: 50 newborns (1-12 months old, six obese), 18 pre-adolescents (7-8 years old, seven obese), and 99 adults (22-80 years old, 32 obese) classified according to standard normal tables and body mass index. Changes of fasting/postprandial gallbladder and gastric motility were assessed simultaneously by functional ultrasonography in response to milk (newborns and pre-adolescents) and to a liquid test meal (adults). In newborns, fasting and postprandial gallbladder volumes and gastric emptying were similar between obese and lean subjects. In pre-adolescents, obese subjects had a larger fasting gallbladder volume, with slower postprandial gastric emptying than lean subjects. In obese adults, the most evident dysfunction emerged, with larger fasting and postprandial residual gallbladder volume, and slower postprandial gastric emptying than lean subjects. Obese subjects display abnormal gallbladder and gastric motility patterns, which first appear in pre-adolescents and deteriorate in adults. Such abnormalities are absent in obese newborns. Functional ultrasonography can detect altered cholecysto-gastric motility at the earliest stage. Our findings suggest an age-related decline of motility, probably secondary to excessive fat and insulin-resistance.

Gastrobiliary motility is not coordinated in patients with non‐ulcer dyspepsia of normal gastric emptying time: Simultaneous sonographic study

Disorders of the motor function of the upper gastrointestinal tract have been implicated in the pathogenesis of non-ulcer dyspepsia. Approximately 50% of patients with abdominal symptoms (without ulcer) have normal gastric emptying. Apart from gastric emptying, other mechanisms are very important in the etiology of non-ulcer dyspepsia. Gastric emptying and gallbladder motility were simultaneously investigated in 16 patients with non-ulcer dyspepsia and in 15 healthy controls. Fasting blood samples were taken, and pepsinogen levels were assayed. Gastric emptying time, fasting antral diameter, and post-prandial antral diameter were not significantly different between the patients with non-ulcer dyspepsia and the controls. Fasting gallbladder volume, the time required to reach minimal gallbladder residual volume, minimal gallbladder residual volume, and the serum levels of pepsinogen were not significantly different. Simple linear regression was used to summarize the relationship between gastric emptying time and time required to reach minimal gallbladder residual volume. In the controls, the gastric emptying time and time required to reach minimal gallbladder residual volume were linearly related. However, in the patients with non-ulcer dyspepsia, they were not related. These observations suggest that disturbance of coordination between gastric emptying and gallbladder emptying is a cause of the symptoms of non-ulcer dyspepsia.

Impaired gallbladder motility and delayed orocecal transit contribute to pigment gallstone and biliary sludge formation in beta-thalassemia major adults.

Gallbladder and gastrointestinal motility defects exist in gallstones patients and to a lesser extent in pigment gallstone patients. To investigated the role of gallbladder and gastrointestinal motility disorders in pigment gallstone formation in beta-thalassemia major. Twenty-three patients with beta-thalassemia major (16 females; age range 18-37 years) and 70 controls (47 females, age range 18-40 years) were studied for gallbladder and gastric emptying (functional ultrasonography), orocecal transit (OCTT, H(2)-breath test), autonomic dysfunction (sweat-spot, cardiorespiratory reflex tests), bowel habits, gastrointestinal symptoms and quality of life (all with questionnaires). Gallbladder content (ultrasonography) was examined before and during 8-12 mo follow-up. Gallstones and/or biliary sludge were found in 13 (56%) patients. beta-thalassemia major patients had increased fasting (38.0+/-4.8 mL vs 20.3+/-0.7 mL, P = 0.0001) and residual (7.9+/-1.3 mL vs 5.1+/-0.3 mL, P = 0.002) volume and slightly slower emptying (24.9+/-1.7 min vs 20.1+/-0.7 min, P = 0.04) of the gallbladder, together with longer OCTT (132.2+/-7.8 min vs 99.7+/-2.3 min, P = 0.00003) than controls. No differences in gastric emptying and bowel habits were found. Also, patients had higher dyspepsia (score: 6.7+/-1.2 vs 4.9+/-0.2, P = 0.027), greater appetite (P = 0.000004) and lower health perception (P = 0.00002) than controls. Autonomic dysfunction was diagnosed in 52% of patients (positive tests: 76.2% and 66.7% for parasympathetic and sympathetic involvement, respectively). Patients developing sludge during follow-up (38%, 2 with prior stones) had increased fasting and residual gallbladder volume. Adult beta-thalassemia major patients have gallbladder dysmotility associated with delayed small intestinal transit and autonomic dysfunction. These abnormalities apparently contribute together with haemolytic hyperbilirubinemia to the pathogenesis of pigment gallstones/sludge in beta-thalassemia major.

Sonographic evaluation of gallbladder volume and ejection fraction in obese women without gallstones.

Obese people have an increased incidence of gallstones. Although the exact pathogenic mechanisms of gallstone development are unknown, impaired gallbladder emptying has been suggested as a possible underlying mechanism. Our aim was to investigate this possibility by evaluating gallbladder motility and related factors in obese and nonobese women without gallstones. This study included 79 obese women and 25 nonobese healthy women. Using real-time sonography, we evaluated fasting and postprandial (15th-, 30th-, 45th-, 60th-, 75th-, 90th-, 120th-, and 150th-minute) gallbladder volumes and ejection fractions. The smallest postprandial volume was considered the residual volume. Mean (+/- standard deviation) fasting and residual gallbladder volumes were 43.2 +/- 18.3 cm(3) and 21.4 +/- 11.2 cm(3), respectively, in the obese women and 28.1 +/- 12.3 cm(3) and 7.9 +/- 3.4 cm(3), respectively, in the nonobese women. Maximal ejection fraction was 49 +/- 19% in obese women and 63 +/- 29% in nonobese women (p = 0.001). The fasting and residual volumes and the postprandial volumes at all time points were higher in obese women than in nonobese women (p < 0.001). In addition, 15th-, 30th-, 45th-, 60th-, 75th-, and 90th-minute postprandial ejection fractions were lower in obese women than in nonobese women (p < 0.001). Positive correlations were found between fasting gallbladder volume and body mass index and body fat weight and between residual volume and body mass index, waist circumference, body fat percentage, and body fat weight (p < 0.05 for all comparisons). Our results show that fasting and postprandial gallbladder volumes are higher and that postprandial gallbladder motility is lower in obese than in nonobese women. There are positive correlations between fasting gallbladder volume and body weight, body mass index, and body fat weight.

Gallbladder contractility in patients with cirrhotic versus malignant ascites.

The aim of this study was to evaluate differences in gallbladder contractility by measuring gallbladder wall thickness, fasting and residual gallbladder volume, and gallbladder ejection fraction in patients with cirrhotic and malignant ascites. Twenty-four patients (16 women and 8 men) with malignant ascites (2 cervical, 2 colon, 2 stomach, 6 pancreatic, and 12 ovarian carcinomas), aged 59 +/- 12 years, and 26 patients (14 women and 12 men) with cirrhotic ascites, aged 57 +/- 16 years, were included in the study. After patients fasted overnight for 8 hours, gallbladder wall thickness, fasting gallbladder volume, and gallbladder volume and ejection fraction were measured sonographically at 10, 20, 30, 40, 50, 60, 70, 80, and 90 minutes after ingestion of a standard liquid test meal. The mean gallbladder wall thickness was higher in patients with cirrhotic ascites than in those with malignant ascites (5.5 +/- 1.5 mm [standard deviation] versus 3.1 +/- 0.6 mm, respectively; p < 0.001). The mean fasting gallbladder volume was also higher in patients with cirrhotic ascites than in those with malignant ascites (27.3 +/- 11.5 cm(3) versus 17.6 +/- 8.9 cm(3); p < 0.05). Patients with cirrhotic ascites had significantly higher mean postprandial gallbladder volumes and ejection fractions than did those with malignant ascites at all times except 10 minutes after the meal (p < 0.05). Our findings suggest that gallbladder contractility is greater in patients with cirrhotic ascites than in patients with malignant ascites.

Cisapride improves gallbladder emptying in patients with type 2 diabetes mellitus.

Gallbladder motor function is impaired in many patients with diabetes, and may be related to cholinergic nerve damage. Cisapride is a prokinetic drug of the gastrointestinal tract and acts by releasing acetylcholine from cholinergic nerve endings. The aim of this study was to determine the effect of cisapride on gallbladder emptying in patients with type 2 diabetes mellitus (DM). Gallbladder emptying and tests for autonomic neuropathy (AN) were performed in 27 patients with type 2 DM and in 10 healthy subjects. Gallbladder emptying was studied by using real-time ultrasonography after an overnight fast, and after the subjects received a breakfast that contained 2500 J. Gallbladder emptying was repeated after the treatment with cisapride (10 mg t.i.d.) for 1 week in all subjects. Abnormal gallbladder emptying was present in 14 (51.9%) patients. The residual gallbladder volume (mean +/- SEM) was higher (9.3 +/- 1.0 vs 4.6 +/- 0.6; P = 0.002), and ejection fraction was lower (57.4 +/- 4.0 vs 74.2 +/- 2.4; P = 0.015) in diabetic patients than it was in healthy subjects. Cisapride produced a reduction in fasting and residual volumes (24.6 +/- 2.4 vs 20.0 +/- 1.4; P = 0.034 and 9.3 +/- 1.0 vs 5.9 +/- 1.1; P = 0.00003, respectively), and an improvement in ejection fraction (57.4 +/- 4.0 vs 72.6 +/- 3.8; P = 0.000007). The improvement in gallbladder emptying after cisapride therapy was confined to the patients with AN (n = 13) (57.3 +/- 5.4 vs 80.4 +/- 2.9; P = 0.0017), suggesting denervation supersensitivity with an upregulation of cholinergic receptors. There was no significant change in the ejection fraction in patients without AN (57.5 +/- 6.1 vs 65.4 +/- 6.5; P = NS). Sex, duration of diabetes, peripheral neuropathy, diabetic retinopathy and serum cholesterol level did not influence gallbladder emptying. Impaired gallbladder emptying is common in patients with type 2 DM. Cisapride significantly improves gallbladder emptying in patients with autonomic neuropathy.

Sluggish small bowel motility is involved in determining increased biliary deoxycholic acid in cholesterol gallstone patients.

Our aim was to establish whether small intestine transit time is defective in subjects with cholesterol gallstones. We enrolled 10 patients (eight women, two men; mean age, 48.7 yr; mean body mass index [BMI], 22.4 Kg/m2) with recently diagnosed cholelithiasis, with no liver pathology, who were not taking any drugs, and 11 comparable healthy volunteers (eight women, three men; mean age, 46.2 yr; mean BMI, 22.7 Kg/m2), who served as controls. All subjects underwent orocecal (by starch breath test technique and serum assays of salazopyrin), oroileal (by serum assays of tauroursodeoxycholic acid), and duodenoileal (by serum assays of taurocholic acid) transit times; cholesterol saturation index; and bile acid composition and gallbladder motility studies (by ultrasound). For serum assays, blood samples were collected over a period of 7 h. Gallbladder motility and orocecal transit time were evaluated simultaneously. All four means of assessing transit time gave longer times in cholesterol gallstone patients than in controls: orocecal transit time (salazopyrin) = 366 +/- 13 vs 258 +/- 16 min, p < 0.0005; orocecal transit time (starch breath test) = 415 +/- 139 vs 290 +/- 15 min, p < 0.01; duodenoileal transit time: 272 +/- 23 vs 205 +/- 23 min, p < 0.03; and oroileal transit time: 308 +/- 18 vs 230 +/- 19 min, p < 0.009. Cholesterol gallstone patients showed an increase in percent molar biliary deoxycholic acid (30% +/- 4.5% vs 16% +/- 1.3%, p < 0.02) and a decrease in percent molar cholic acid 32% +/- 2.2% vs 40% +/- 1.3%, p < 0.03) and chenodeoxycholic acid (34% +/- 3% vs 41% +/- 1.8%, p < 0.03), compared with controls; patients also had greater percent molar biliary cholesterol. A linear relationship (r2 = 0.6324, p = 0.0012) between biliary deoxycholic acid and small bowel transit time was found. Residual gallbladder volumes were larger in cholesterol gallstone patients (11.38 +/- 1.27 vs 7.55 +/- 0.39 ml, p < 0.04), whereas basal gallbladder volumes, although higher, did not reach statistical significance (24.25 +/- 2.41 vs 19.98 +/- 1.63 ml; p = ns). This study confirms that patients with cholesterol gallstones have delayed small bowel transit, defective gallbladder motor function, and increased biliary deoxycholic acid. Delayed small bowel transit may contribute to supersaturation of bile with cholesterol by increasing deoxycholic acid production.

Sluggish small bowel motility is involved in determining increased biliary deoxycholic acid in cholesterol gallstone patients

OBJECTIVE: Our aim was to establish whether small intestine transit time is defective in subjects with cholesterol gallstones. METHODS: We enrolled 10 patients (eight women, two men; mean age, 48.7 yr; mean body mass index [BMI], 22.4 Kg/m 2) with recently diagnosed cholelithiasis, with no liver pathology, who were not taking any drugs, and 11 comparable healthy volunteers (eight women, three men; mean age, 46.2 yr; mean BMI, 22.7 Kg/m 2), who served as controls. All subjects underwent orocecal (by starch breath test technique and serum assays of salazopyrin), oroileal (by serum assays of tauroursodeoxycholic acid), and duodenoileal (by serum assays of taurocholic acid) transit times; cholesterol saturation index; and bile acid composition and gallbladder motility studies (by ultrasound). For serum assays, blood samples were collected over a period of 7 h. Gallbladder motility and orocecal transit time were evaluated simultaneously. RESULTS: All four means of assessing transit time gave longer times in cholesterol gallstone patients than in controls: orocecal transit time (salazopyrin) = 366 ± 13 vs 258 ± 16 min, p < 0.0005; orocecal transit time (starch breath test) = 415 ± 139 vs 290 ± 15 min, p < 0.01; duodenoileal transit time: 272 ± 23 vs 205 ± 23 min, p < 0.03; and oroileal transit time: 308 ± 18 vs 230 ± 19 min, p < 0.009. Cholesterol gallstone patients showed an increase in percent molar biliary deoxycholic acid (30% ± 4.5% vs 16% ± 1.3%, p < 0.02) and a decrease in percent molar cholic acid 32% ± 2.2% vs 40% ± 1.3%, p < 0.03) and chenodeoxycholic acid (34% ± 3% vs 41% ± 1.8%, p < 0.03), compared with controls; patients also had greater percent molar biliary cholesterol. A linear relationship (r 2 = 0.6324, p = 0.0012) between biliary deoxycholic acid and small bowel transit time was found. Residual gallbladder volumes were larger in cholesterol gallstone patients (11.38 ± 1.27 vs 7.55 ± 0.39 ml, p < 0.04), whereas basal gallbladder volumes, although higher, did not reach statistical significance (24.25 ± 2.41 vs 19.98 ± 1.63 ml; p = ns). CONCLUSIONS: This study confirms that patients with cholesterol gallstones have delayed small bowel transit, defective gallbladder motor function, and increased biliary deoxycholic acid. Delayed small bowel transit may contribute to supersaturation of bile with cholesterol by increasing deoxycholic acid production.

Gall bladder motility after endoscopic sphincterotomy

Editor,—We read with interest the article by Sugiyama and Atomi ( Gut 1996; 39 :856–9) on the effect of endoscopic sphincterotomy (ES) on gall bladder motility. These authors have proved conclusively that ES causes a significant improvement in gall bladder motility in humans. We have assessed gall bladder motility in patients who underwent ES for common bile duct (CBD) stones and compared these with patients with gall bladder calculi but without CBD stones. We found significantly lower fasting and residual gall bladder volumes in the patients who had undergone ES, indicating reduced filling after ES.1 However, the ejection fraction and the rate constant of gall bladder emptying in these patients was increased significantly, suggesting increased gall bladder emptying. In another study2 we found a significant decrease in fasting volume (mean (SD) 18.3 (8.5) v 13.9 (7.3) ml), residual volume (12.0 (8.0) v 4.4 (3.2) ml) and an increase in the ejection fraction (54.3 (9.8) v 83.5 (5.4)) after ES, suggesting decreased stasis and increased gall bladder emptying. In Sugiyama and Atomi’s this study, all patients in whom gall bladder motility was assessed before ES had CBD stones; all stones were extracted before … Dr Sugiyama.

Impaired gallbladder and gastric motility and pathological gastro-oesophageal reflux in gallstone patients.

Impaired gallbladder motility is common in gallstone patients and might be associated with other gastrointestinal defects. Twenty patients with small stones in an opacified gallbladder at oral cholecystography and 20 healthy subjects homogeneous for sex, age and body size were studied by ultrasonography to assess gallbladder and gastric emptying simultaneously in response to a standard liquid meal (120 kcal, 11 g fat, 200 mL). The same subjects underwent ambulatory 24-h gastro-oesophageal pH monitoring. Dyspeptic symptoms were specifically investigated using a questionnaire. Gallstone patients had a significantly larger fasting (P < 0.05) and residual (P < 0.005) gallbladder volume with slower (P < 0.05) and less complete (ANOVA, 0.001 < P < 0.05) gastric emptying than healthy control subjects. The speed of antral emptying was significantly correlated with the speed of gallbladder emptying (n = 40, r = +0.31, P < 0.05). Pathological gastro-oesophageal reflux was present in 75% and 15% of patients and control subjects respectively (P < 0.05). Overall, 95% of gallstone patients had abnormal pH profiles resulting from pathological gastro-oesophageal reflux and/or prolonged gastric alkalinization. The speed of post-prandial antral emptying was significantly correlated with the duration of the longest gastro-oesophageal reflux episode (r = +0.30, P < 0.03) and duodeno-gastric reflux episode (r = +0.80, P < 0.02). Best predictors for gastric alkalinization were the following indices of gallbladder function: large fasting volume (P = 0.03), large ejection volume (P = 0.009) and slower emptying (P = 0.032). Gallbladder and gastric motility were similar in patients with (n = 12) and without (n = 8) dyspeptic symptoms. Pathological gastro-oesophageal reflux was found in 83% of dyspeptic patients and in 25% of patients without dyspepsia (P < 0.01). When reflux was present, it was significantly less in asymptomatic than in dyspeptic patients [time at pH < 4, median (range): 6.4% (3.2-22.6%) vs. 47.8% (2.1-87%), P < 0.05]. This study shows that a subgroup of gallstone patients with small-mainly asymptomatic-stones have impaired gallbladder and gastric motility as well as abnormal gastro-oesophageal pH-profiles. These findings point to the existence of multiple functional defects of the upper gastrointestinal tract in gallstone disease.

Gallbladder motility and lithogenicity of bile in patients with choledocholithiasis after endoscopic sphincterotomy

Background/Aims: Ablation of the sphincter of Oddi has been shown to inhibit gallstone formation in the prairie dog model, probably by allevaiting gallbladder bile stasis. The effect of endoscopic sphincterotomy (ES) on gallbladder emptying and lithogenicity of bile has not been studied adequately in humans. We, therefore, studied the changes in gallbladder emptying and lithogenicity of bile following ES in patients with choledocholithiasis and gallbladder in situ. Methods: Thirteen patients with choledocholithiasis with intact gallbladder underwent ES and common bile duct clearance. Eight patients had concomitant gallstones. Gallbladder emptying was studied by real time ultrasonography after stimulation by ceruletid infusion. Fasting gallbladder bile was collected during endoscopic retrograde cholangiography by placing a 7F or 8F catheter in the common bile duct and after ceruletid stimulation of gallbladder for bile microscopy and cholesterol nucleation time determination. Gallbladder emptying, nucleation time and bile microscopy were performed before ES and again between 4 and 8 weeks after ES after cholangiographic confirmation of clearance of common bile duct stones. Results: Fasting and residual gallbladder volumes decreased and ejection fraction increased significantly following ES, suggesting decreased stasis and improved emptying of gallbladder. Nucleation time was prolonged and cholesterol crystal index in bile decreased after ES, suggesting decreased lithogenicity. The decrease in gallbladder volumes and increase in ejection fraction after ES were observed in both groups of patients, with or without concomitant gallstones. Conclusions: ES decreases the stasis of gallbladder bile, improves gallbladder emptying and decreases the lithogenicity of bile in patients with gallstone disease as reflected by prolongation in nucleation time. ES may find a role as an adjunct to oral bile acid therapy and extracorporeal shock wave lithotripsy in addition to a prophylactic role of preventing gallstone formation in high risk groups.

Gallbladder hypokinesia in Crohn's disease.

For the purpose of shedding some light upon the possible mechanisms involved in gallstone formation in patients with Crohn's disease, we have investigated gallbladder emptying by means of ultrasonography in two groups of subjects: controls (n = 40) and Crohn's disease (n = 30). Diminished gallbladder emptying after a liquid fatty-meal stimulus was observed in patients with Crohn's disease when compared with controls (p < 0.001). Also, the values for the residual gallbladder volume (RGV) and maximal decrease in gallbladder volume (MDGV), both in milliliters and percentage were, respectively, increased (RGV = 9.6 ml) and diminished (MDGV = 14.8 ml; MDGV = 60.9%) in patients with Crohn's disease when compared with controls (RGV = 5.9 ml, p < 0.001; MDGV = 19.9 ml, p = 0.003; MDGV = 77.8%, p < 0.001). Hence, reduced gallbladder emptying with consequent stasis might be a contributory factor to the increased prevalence of gallstones in Crohn's disease.

Effect of endoscopic sphincterotomy on gallbladder motility.

In experimental animals, sphincterotomy facilitates passage of solids from the gallbladder and inhibits gallstone formation apparently by improvement in gallbladder emptying. In humans, however, gallbladder emptying has not been studied following endoscopic sphincterotomy (ES) in patients with gallstones. We therefore prospectively studied resting and cerulin-stimulated gallbladder volumes by real time ultrasonography in 15 patients of choledocholithiasis with gallbladder in situ (eight with and seven without gallbladder calculi) before and after (after bile duct clearance) ES. ES significantly lowered resting gallbladder volume (21.2 +/- 10.6 vs 11.1 +/- 5.0; P < 0.0001) and cerulin-stimulated residual gallbladder volume (10.8 +/- 5.6 vs 4.4 +/- 2.1; P < 0.0001). ES also significantly increased the gallbladder ejection fraction (47.3 +/- 12.1% vs 58.8 +/- 11.1%; P < 0.0001). The rate constant for gallbladder emptying after cerulin infusion also increased significantly after ES (-0.022/min vs -0.031/ min; P < 0.0001). Significant improvement in gallbladder motility was observed in both groups of patients with and without gallbladder calculi. ES significantly improves gallbladder motility in humans.

Apolipoprotein E4 genotype and gallbladder motility influence speed of gallstone clearance and risk of recurrence after extracorporeal shock-wave lithotripsy.

Extracorporeal shock-wave lithotripsy (ESWL) is an effective treatment in selected gallstone patients, but stone recurrence is a major drawback. Factors potentially influencing gallstone clearance and recurrence were studied in 84 patients in whom stone dissolution was diagnosed after ESWL plus bile salt therapy for initial solitary (n = 55) or multiple (n = 29) radiolucent stones. Apolipoprotein E (apoE) genotyping and gallbladder motility (sonography) were studied in a representative subgroup of patients (n = 50). The median follow-up after ESWL was 36 months (range, 4.5-67 months). Gallstone clearance was achieved after 8.7 months (range, 0.2-30 months). Independent factors significantly enhancing gallstone clearance were the presence of E4 allele; small initial gallstone size and number; effectiveness of fragmentation; and good gallbladder emptying (P = .002). Gallstone recurrence was seen in 30 patients after 18.6 months (range, 1.0-50 months). Cumulative gallstone recurrence rate (life-table analysis) was 15% within 1 year, increasing to 60% within 5.5 years. Although the probability of gallstone recurrence tended to be smaller in patients with initial solitary stones than in those with multiple stones during early follow-up, differences disappeared after long-term follow-up. Effective gallbladder emptying (residual volume < or = 6 mL) and apolipoprotein E4 (apoE4) independently influenced gallstone recurrence. Recurrence rate was higher (log rank test, P = .037) in those patients who were homozygous and heterozygous for the E4 allele compared with the individuals who were not expressing the apoE4 allele. Accordingly, there was an overrepresentation of the allele frequency for E4 in the group with gallstone recurrence (P =.03). Patients with small postprandial residual gallbladder volumes (</= 6 mL) had a lower probability of stone recurrence than those with large residual gallbladder volumes (log rank test, P = .0215). Biliary pain was more frequent with recurrence (55% vs. 13%, P = .001). The present study indicates that apoE4 genotype is associated with increased speed of gallstone clearance as well as a high risk of recurrence after ESWL. This finding points to a possible role for genetic factors in the pathogenesis of cholesterol gallstones. Effective gallbladder emptying is important for speed of clearance and prevention of recurrence. Patients with initial solitary stones have a decreased early- but not long-term gallstone recurrence rate.

Apolipoprotein E4 genotype and gallbladder motility influence speed of gallstone clearance and risk of recurrence after extracorporeal shock-wave lithotripsy

Extracorporeal shock-wave lithotripsy (ESWL) is an effective treatment in selected gallstone patients, but stone recurrence is a major drawback. Factors potentially influencing gallstone clearance and recurrence were studied in 84 patients in whom stone dissolution was diagnosed after ESWL plus bile salt therapy for initial solitary (n = 55) or multiple (n = 29) radiolucent stones. Apolipoprotein E (apoE) genotyping and gallbladder motility (sonography) were studied in a representative subgroup of patients (n = 50). The median follow-up after ESWL was 36 months (range, 4.5-67 months). Gallstone clearance was achieved after 8.7 months (range, 0.2-30 months). Independent factors significantly enhancing gallstone clearance were the presence of E4 allele; small initial gallstone size and number; effectiveness of fragmentation; and good gallbladder emptying (P = .002). Gallstone recurrence was seen in 30 patients after 18.6 months (range, 1.0-50 months). Cumulative gallstone recurrence rate (life-table analysis) was 15% within 1 year, increasing to 60% within 5.5 years. Although the probability of gallstone recurrence tended to be smaller in patients with initial solitary stones than in those with multiple stones during early follow-up, differences disappeared after long-term follow-up. Effective gallbladder emptying (residual volume < or = 6 mL) and apolipoprotein E4 (apoE4) independently influenced gallstone recurrence. Recurrence rate was higher (log rank test, P = .037) in those patients who were homozygous and heterozygous for the E4 allele compared with the individuals who were not expressing the apoE4 allele. Accordingly, there was an overrepresentation of the allele frequency for E4 in the group with gallstone recurrence (P =.03). Patients with small postprandial residual gallbladder volumes (≤ 6 mL) had a lower probability of stone recurrence than those with large residual gallbladder volumes (log rank test, P = .0215). Biliary pain was more frequent with recurrence (55% vs. 13%, P = .001). The present study indicates that apoE4 genotype is associated with increased speed of gallstone clearance as well as a high risk of recurrence after ESWL. This finding points to a possible role for genetic factors in the pathogenesis of cholesterol gallstones. Effective gallbladder emptying is important for speed of clearance and prevention of recurrence. Patients with initial solitary stones have a decreased early- but not long-term gallstone recurrence rate. (Hepatology 1996 Sep;24(3):580-7)

Effect of extracorporeal shock-wave lithotripsy on gallbladder emptying in patients with solitary and multiple gallbladder stones

In a prospective study, we investigated the effect of extracorporeal shock-wave lithotripsy (ESWL) on gallbladder contractility and on fasting and residual gallbladder volume in patients with solitary and multiple gallbladder stones with stone densities < 100 Hounsfield units (HU) and adequate gallbladder function. Twenty-five patients (seven males and 18 females, mean age 48.5 +/- 11.7 years) treated with ESWL were assigned to either group I, consisting of 13 patients with solitary stones < 20 mm diameter, or group II, including patients with two to three stones and maximum stone diameter of 30 mm. ESWL was performed with the MPL 9000 lithotripter. Gallbladder ejection fraction was determined using the method of Dodds after a 12-hr fast and following application of a standard stimulative meal. Gallbladder volume was measured by ultrasound over 90 min at 10-min intervals before ESWL, then at 1, 30, 120, and 210 days after ESWL. At 24 hr after ESWL, residual gallbladder volume increased in group I from 7.4 ml to 13.9 ml (P = 0.0567) and in group II from 6.5 ml to 20.2 ml (P = 0.0076). Thereafter, residual volumes returned to pre-ESWL levels. In group II, post-ESWL fasting volumes were significantly increased over initial values at all time intervals. Correspondingly, only at 24 hr after ESWL, ejection fractions decreased from 73.1% to 64.9% in group I and from 76.5% to 62.7% in group II. No statistically significant differences in gallbladder contractility between the two groups were observed at any point of the follow-up period.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of oral erythromycin on gallbladder motility in normal subjects and subjects with gallstones

The action of the motilin receptor agonist erythromycin on human gallbladder contraction, measured by ultrasound, both in normal subjects and those with gallstone disease was studied. In 17 normal subjects, oral erythromycin administration (500 mg; vs. placebo) reduced fasting gallbladder volume at 2 hours (26.2 vs. 19.0 mL; P < 0.001), and postprandial residual gallbladder volume (9.0 vs. 4.4 mL; P < 0.001) and the rate constant of gallbladder emptying following the meal was significantly increased. Erythromycin also reduced fasting and residual gallbladder volumes in 13 patients with gallstone disease: in 6 who underwent cholecystolithotomy, fasting volume was 29.5 vs. 22.3 mL (P < 0.05) and residual volume was 17.7 vs. 6.5 mL (P < 0.05), and in 7 with gallstones in situ, fasting volume was 23.8 vs. 14.3 mL (P < 0.05) and residual volume was 17.2 vs. 5.0 mL (P < 0.05). In 7 of 8 subjects with gallstones and impaired gallbladder emptying, the gallbladder emptied normally following administration of erythromycin, and in 3 of the other 5 gallstone subjects gallbladder emptying was increased. In 6 normal subjects given erythromycin three times weekly for 1 month, the effect was maintained (fasting volume, 18.8 mL, P < 0.001; residual volume, 3.7 mL, P < 0.001). Oral erythromycin significantly reduces fasting and postprandial residual gallbladder volumes in both normal subjects and subjects with gallstones and reverses the gallbladder motility defect found in a proportion of subjects with gallstones. This effect is maintained for a month in normal subjects.