Search

Objective: Gallbladder removal is associated with an increased incidence of gastroesophageal reflux, but the mechanism is unclear. Cholecystokinin (CCK) release, which causes gallbladder contraction, is inhibited by bile in the duodenum. This study investigates the effect of cholecystectomy on meal-stimulated CCK secretion., Methods: Three groups of patients were studied. Group 1 (n = 15) were normal controls. Group 2 (n = 27) were patients with symptomatic gallstones. Group 3 (n = 25) were patients who had undergone cholecystectomy. Meal-stimulated CCK levels were measured by radioimmunoassay at defined time points for 60 min after a standard corn oil-based meal., Results: Fasting CCK levels were similar in all three groups. In postcholecystectomy patients, meal-stimulated plasma CCK levels were significantly elevated compared with controls: median (range) integrated CCK values for 60 min were 116 (28-209) in controls, 123 (20-501) in gallstone patients, and 176 (63-502) after cholecystectomy., Conclusions: This study suggests that cholecystectomy causes an exaggerated meal-stimulated CCK response. Because CCK is known to relax the lower esophageal sphincter. these findings may help explain the increased incidence of gastroesophageal reflux seen after cholecystectomy.

Objectives: We aimed to determine whether early trends in the serum pancreatic enzymes and liver tests of patients with gallstone pancreatitis predict persistent common bile duct (CBD) stones and complications., Methods: Medical records of patients with gallstone pancreatitis were reviewed retrospectively. Serial serum pancreatic enzymes and liver tests were recorded until the time of cholangiography. Laboratory trends were analyzed by comparing initial results obtained in the emergency department to subsequent results obtained 8-24 h, 24-48 h, and 48-72 h after presentation., Results: Of 154 patients with gallstone pancreatitis, 28 (18%) had persistent CBD stones at cholangiography. Complications and death were more frequent in patients with persistent CBD stones than in those without CBD stones (29% and 11% vs 12% and 1%, respectively; p < 0.05). Laboratory trends predicted both persistent CBD stones and complications of pancreatitis. When any laboratory value rose between admission and 24-48 h of hospitalization, persistent CBD stones were present in 31% of cases, versus 8% of those in whom all laboratory values remained constant or fell (p = 0.001). Likewise, complications occurred in 21% of those with any rising laboratory value, versus 8% of those in whom all values remained constant or fell (p < 0.05)., Conclusions: Patients with gallstone pancreatitis and rising serum chemistries had a 4-fold risk of persistent CBD stones and a nearly 3-fold risk of complications compared to patients in whom all chemistry values remained constant or fell. This simple prediction rule may identify patients with biliary pancreatitis who are most likely to benefit from early interventions to diagnose and remove persistent CBD stones.

Objective: Gastrectomy might be a risk factor for cholelithiasis and gallbladder stasis might play a major role. We studied fasting and postprandial gallbladder motility with 600 mg oral erythromycin or placebo in gastrectomized patients (with and without gallstones) and controls., Methods: Seventeen patients operated on for gastric cancer (subtotal gastrectomy: n = 10, total gastrectomy: n = 7) were compared with 20 sex- and body-size matched healthy controls. Subjects randomly received erythromycin or placebo 30 min before the ingestion of a standard 200 ml liquid test meal. Gallbladder volume was estimated by ultrasonography until 120 min after test meal. A visual analog scale monitored GI perception of appetite, satiety, nausea, abdominal fullness and epigastric pain., Results: Gastrectomized patients had increased fasting gallbladder volume (35.9 +/- 3.4 ml versus 21.0 +/- 1.4 ml, p = 0.0005) with faster postmeal emptying (T/2 14.8 +/- 1.1 min versus 23.5 +/- 1.5 min, p = 0.00019) than controls. Six patients developed small and asymptomatic gallstones, which did not influence gallbladder motility. In these patients, fasting gallbladder volume increased with time after surgery (r = +0.82, p = 0.047). Perception of satiety, abdominal fullness, and epigastric pain after ingestion of the test meal were all significantly greater in patients than in controls. Erythromycin significantly enhanced gallbladder emptying during fasting (p = 0.001) and postprandially in both patients and controls (0.002 < p < 0.017) and significantly reduced postmeal satiety and epigastric discomfort in gastrectomized patients., Conclusions: Increased fasting volume might be a form of stasis, predisposing patients to gallstone formation. Erythromycin improves fasting and postprandial gallbladder emptying and decreases upper GI symptoms in gastrectomized 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/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., 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 (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)., 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.

Intestinal transit has a substantial influence on the enterohepatic circulation of bile acids and steroid hormones, on colonic pH, and on short chain fatty acid concentrations in the distal colon. Slow transit is likely to favor disease processes that are related to over-efficient enterohepatic recirculation and to lack of short chain fatty acid in the distal colon. These include gallstones, large bowel cancer, and possibly breast cancer. The best-documented influence of slow colonic transit is on bile acid metabolism. Slowing colonic transit increases deoxycholate and raises cholesterol saturation of bile, making gallstone formation more likely. In this review, we also examine the evidence that slow colonic transit may be important in the etiology of large bowel and breast cancer. There is a lack of data pertaining to the relationship between colonic transit and diseases such as colon and breast cancer. Should slow colonic transit prove to be a significant factor in the etiology of such diseases, then the health of the population might benefit from dietary and lifestyle changes that speed up intestinal transit.

Objective: Extra corporeal shock wave lithotripsy is a promising and effective therapy mode in the nonsurgical therapy of gallstones. This prospective study was conducted to investigate the effects of ESWL on hepatocellular function, using quantitative hepatobiliary scintigraphy, serum aminotransferase, alkaline phosphatase (ALP), amylase (AML), and direct and indirect bilirubin levels., Methods: The study consisted of 22 patients with ultrasonographically documented gallstones. Hepatobiliary scintigraphy was applied to all patients before ESWL and biochemical tests were performed. Scintigraphy and biochemical tests were repeated in 16 patients 24 h, in seven patients 72 h, and in six patients 1 wk after ESWL. The hepatic extraction fraction (HEF) was calculated using deconvolution analysis of scintigraphic data., Results: All patients' pre-ESWL biochemical tests and HEF values were within the normal range. The 24- and 72-h post-ESWL aminotransferase, ALP, and AML levels and HEF values were significantly different from pre-ESWL values (p < 0.05). After 1 wk this difference disappeared. Decreased HEF values were observed in 50% of patients 24 h, in 71.7% of patients 72 h, and in 16.6% of patients 1 wk after ESWL. A direct relationship was also observed between the number of shocks applied and the degree of impairment in HEF values., Conclusion: Transient hepatocellular dysfunction, which usually occurs after ESWL, can be demonstrated and monitored using quantitative hepatobiliary scintigraphy.

Objectives: The sphincter of Oddi (SO) manometry via the transpapillary route is performed usually for a period of several minutes. To investigate whether there is a considerable variation in the manometric measurements of SO over a longer period of time, we have performed long-term manometry of SO via the transpapillary (n = 5) as well as the percutaneous (n = 7) routes., Methods: Transpapillary manometry of SO was carried out by a conventional low-compliant continuously perfused technique. The location of the manometric catheter was maintained at the same level by observing the video monitor. SO manometry and the duodenal migrating motor complex (MMC) was simultaneously measured with a specially designed catheter via the percutaneous route., Results: The mean recording time was 41 min (range 11-72 min). The frequency of phasic contractions of SO varied from 0 to 12/min. Throughout the entire recording period, high-frequency contractions (over 8/min) were noted 14.9% of the time. In the cases of percutaneous transductal SO manometry, the periods of high-frequency contractions coincided with phase III of duodenal MMC. The interval between the first high-frequency contractions and the second was 47 min. The mean duration of high-frequency contractions was 6 min and 42 s. There was no significant change in the amplitude, basal pressure, and contraction sequence among the various periods of frequencies., Conclusions: Long-term continuous recording of SO manometry via the transpapillary and percutaneous routes showed that the contraction frequency of SO was not constant and tachyoddia appeared periodically. In the interpretation of tachyoddia, it is necessary to consider the period of phase III of the duodenal MMC.

Objective: Laparoscopic cholecystectomy (LC) has become the choice of treatment for symptomatic gallbladder stones. The goal of this study was to predict the necessity for ERCP before LC using the noninvasive method of liver function testing (LFT) and sonography., Methods: Before LC, 115 symptomatic gallbladder stone patients, whose diagnoses were confirmed by sonography, were studied by both LFT and ERCP. Patients who were already found to have either tumors or intrahepatic biliary stones on sonogram were excluded. Patients were classified into normal and dilated biliary tree groups by sonographic findings and normal and abnormal LFT (including bilirubin, alkaline phosphatase, gamma glutamyl transferase and amylase) groups., Results: In patients with both normal biliary sonogram and LFT, 97.6% of patients had a negative ERCP study. Biliary tree dilation on sonogram had an 87% positive predictability for ductal pathology on ERCP (40/46). A normal biliary tree on sonogram had a 17.4% incidence of positive ductal pathology on ERCP (12/69). A single abnormal LFT equated to a 68.8% positive predictability for ductal pathology on ERCP., Conclusion: ERCP is not necessary before LC for patients with symptomatic gallbladder stones who have both a normal biliary tree on sonogram and normal LFT. A patient with either a dilated bile duct on sonogram or an abnormal liver function test does require ERCP study.

Octreotide exerts a wide range of biological actions, many of which have important clinical applications, notably in treatment of acromegaly, gastroenteropancreatic endocrine tumors, and secretory diarrhea. In most patients, octreotide is well tolerated. Side effects are primarily gastrointestinal and are usually transient. Short term (< or = 1 month) octreotide therapy appears to pose minimal risk of gallstone formation, but the risk may increase with longer treatment periods. Chronic octreotide administration may increase the incidence of small, cholesterol gallstones that are typically asymptomatic. The mechanism of octreotide-associated gallstone formation is not delineated but may involve inhibition of gallbladder emptying, hepatic bile secretion, and sphincter of Oddi motility, as well as modification of bile composition. Gallbladder stasis may sequentially lead to increased bile concentration, precipitation of cholesterol and calcium salts, retention of biliary precipitates, and maturation of gallstones. Octreotide-associated gallstones are usually asymptomatic and do not require surgical or medical therapy. Some physicians advocate periodic gallbladder ultrasound evaluations, but, in most cases, the results would not influence management of asymptomatic patients. Symptomatic gallstones may require surgery or nonsurgical treatments after an appropriate work-up. Gallstone prevention strategies (e.g., bile acid or nonsteroidal anti-inflammatory drug therapy) during long term octreotide therapy are under investigation. Currently, clinicians may want to consider noninvasive strategies to reduce gallstone incidence, such as timing octreotide injections in relation to meals or periodic cessation of octreotide treatment. Octreotide is a valuable therapeutic option in managing a variety of hypersecretory states associated with high morbidity and mortality (e.g., acromegaly, carcinoid syndrome, and VIP-secreting tumors), so the benefits of long term octreotide therapy (such as increased quality of life) outweigh the risk of asymptomatic gallstone formation in many patients.

Objective: Considerable information is presently available about stone-free rates after extracorporeal shock wave lithotripsy (ESWL) of gallbladder stones. Another important item and one that has been poorly investigated is symptom relief after successful ESWL. The aim of the present trial was to determine the course of biliary and gastrointestinal symptoms after successful ESWL of gallstones., Methods: Ninety patients were followed for an average of 18 months after stone disappearance and discontinuation of oral bile acids. A standardized questionnaire was combined with a clinical and ultrasound examination. Relief of symptoms was correlated to patient characteristics, stone volume, and gallbladder functions., Results: Twelve patients (13%) developed recurrent stones. The probability of stone recurrence was 5.5% (+/- 2.5%) after 1 yr, 12% (+/- 4.5%) after 2 yr, and 30.5% (+/- 9.5%) after 3 yr. Sixty-two of 78 stone-free patients were asymptomatic (80%). Most patients lost their typical biliary symptoms, but statistics also revealed significant differences of nonspecific symptoms and food intolerances pre- and postlithotripsy., Conclusions: This trial has confirmed that patients with symptomatic gallstone disease exhibit a wide spectrum of symptoms, many of which are relieved by ESWL. The fact that at least every fifth patient is not free of symptoms after the gallstone has been removed is in keeping with the findings after cholecystectomy. According to our data, recurrence rate after successful ESWL is higher than previously reported and similar to results after oral litholysis, with no differences between single and multiple stones.

Objective: To evaluate whether a low dose of oral cholestyramine improves gallbladder emptying in gallstone patients., Methods: Gallbladder volumes were assessed by sonography in 36 patients with cholesterol gallstones and 18 healthy controls. On three different days subjects ingested: 1) test meal alone, 2) test meal plus cholestyramine (4 g), and 3) cholestyramine alone (4 g)., Results: Fasting gallbladder volume (mean +/- SE, 25.9 +/- 1.8 ml and 19.2 +/- 1.3 ml for patients and controls, respectively, p < 0.05) and postprandial gallbladder residual volume (48.7 +/- 3.9% and 21.6 +/- 2.8% of fasting volume in patients and controls, respectively, p < 0.001) were larger in patients than controls, indicating impaired gallbladder emptying. Gallstone patients were divided into 19 "contractors" and 17 "hypocontractors" (residual gallbladder volume smaller or greater than mean +/- 2 SD of controls). Compared with the test meal alone, the addition of cholestyramine induced a further decrease of residual volume in contractors (from 30.4 +/- 2.1% to 19.8 +/- 1.9%, p < 0.001), hypocontractors (from 69.3 +/- 3.9% to 56.7 +/- 7.4%, p < 0.05), and controls (from 21.6 +/- 2.8% to 5.0 +/- 1.0%, p < 0.0004). Two hours after test meal plus cholestyramine gallbladder volume was still markedly reduced in both patients and controls. Fasting gallbladder volume 24 h after test meal plus cholestyramine was decreased in patients and in controls. The ingestion of cholestyramine alone initiated gallbladder evacuation comparable to that of test meal in both contractors and hypocontractors., Conclusions: A low dose of cholestyramine in combination with test meal induces a considerable decrement of gallbladder volume compared with test meal alone in gallstone patients. Cholestyramine alone causes a decrease of gallbladder volume which is comparable to that observed in response to test meal alone.

Objectives: The present study investigated endogenous postprandial release of cholecystokinin (CCK) and pancreatic polypeptide (PP) in relation to gallbladder dynamics in healthy subjects and patients with gallstones., Methods: Gallbladder volume (by ultrasonography) and plasma concentrations of CCK and PP (by radioimmunoassay) were evaluated in 18 patients with gallstones and 14 healthy controls before and after administration of a semi-liquid test meal (250 ml, 1450 kJ). Gallbladder contractility was previously assessed on a separate day by intravenous infusion of ceruletide (2.5 ng/kg/min)., Results: Basal gallbladder volume was not different in patients (32 +/- 5.9 cm3) and controls (26 +/- 2.7 cm3). Postprandial gallbladder contractility was impaired in gallstone patients, who showed a reduced integrated response (-3718 +/- 349 vs. -5251 +/- 376 cm3/2 h, p < 0.01) and a delayed time to maximal gallbladder contraction (67 +/- 7.4 min vs. 37 +/- 2.4 min, p < 0.002). Maximal gallbladder contraction after ceruletide infusion was also reduced (44.1 +/- 5.0% vs. 72.5 +/- 3.2%, p < 0.001), but not delayed (15.8 +/- 2.4 vs. 15.7 +/- 1.4 min) in gallstone patients. Basal CCK and PP plasma levels were similar in both groups. Postprandial CCK release was impaired in gallstone patients, predominantly due to a decreased response over the first 30 min (3.8 +/- 1.8 vs. 20.0 +/- 4.9 pmol/L/30 min, p < 0.005). Postprandial PP release was not different between groups. A direct linear correlation between postprandial release of CCK and PP was found in healthy controls but not in patients with gallstones. Postprandial gallbladder volume at any moment was inversely correlated with CCK plasma levels in healthy subjects, but not in gallstone patients. No correlation between postprandial PP response and gallbladder dynamics was observed., Conclusions: Based on a multivariate logistic approach, a reduced and delayed postprandial gallbladder contractility and an impaired CCK release in the early postprandial phase are significantly associated with gallstone disease. Our data provide further evidence for the predominant role of endogenous postprandial CCK release in gallbladder contraction. A role for PP in modulating postprandial gallbladder dynamics is not supported.

In a prospective study of 63 patients, we purposed to determine whether gallbladder contractility or gallbladder volume before biliary lithotripsy are predictors of fragment disappearance. Percentage gallbladder contraction was calculated from the fractional difference in the sonographically measured gallbladder volume after a standard fatty meal. Statistical analysis showed no significant differences in gallbladder contractility between the fragment-free group and the residual-fragment group before (77.2 +/- 12.7% vs. 71.9 +/- 19.3%; p = 0.1044) biliary lithotripsy and after the termination of adjuvant cholelitholysis therapy (76.4 +/- 12.9% vs. 72.2 +/- 17.1%; p = 0.1341). Before treatment, there was no significant difference in fasting gallbladder volume in either group (29.9 +/- 15.4 ml vs. 36.6 +/- 18.8; p = 0.0682), but postprandial gallbladder volume was greater in nonresponders (10.4 +/- 9.4 ml vs. 6.5 +/- 3.8; p = 0.0164). After termination of the therapy, both the fasting gallbladder volume (41.2 +/- 24.2 ml vs. 29.8 +/- 10.3 ml; p = 0.0093) and the postprandial gallbladder volume (11.9 +/- 11.7 ml vs. 7.3 +/- 5.3 ml; p = 0.0267) were greater in the residual-fragment group. The increase of the fasting gallbladder volume in the residual-fragment group was statistically not significant. Our results indicate that the increased residual volume is a significant cause of therapeutic failure in nonresponders.

The prevalence of cholelithiasis (gallstones or previous cholecystectomy) was evaluated in a series of 500 cirrhotic patients from Northern Italy (329 males and 171 females, mean age 58 +/- 11 (SD) yr and 61 +/- 10 yr, respectively). Cirrhosis was related to chronic alcohol abuse in 180 cases, non-A non-B (NANB) hepatitis in 160, hepatitis B virus (HBV) in 94 (including 38 with concomitant alcohol abuse), idiopathic hemochromatosis in 44, and miscellaneous causes in the remaining 22 (including 15 with primary biliary cirrhosis). One hundred and sixteen patients (23.2%) had gallstones, and 31 others (6.2%) had previously undergone cholecystectomy, with an overall prevalence of cholelithiasis of 29.4%. The frequency was similar in both sexes (91/329 males, 27.7% vs. 56/171 females, 32.7%; p = NS), showed a slight increase with age, and differed significantly according to etiology (p less than 0.05), with the highest prevalence in the miscellaneous group and the alcoholics (36.4% and 33.3%, respectively). No significant difference was found in the prevalence of cholelithiasis according to Child's A, B, or C class.

Gallstones are a major health problem in the United States. More than 20 million Americans have gallstones, and a million new cases are discovered each year. A resurgence of interest in this field has been stimulated by advances in understanding the pathogenesis of cholesterol gallstones and in nonsurgical treatments. The purpose of this symposium is to update these advances.

We endoscopically measured pressures of the pancreatic duct (PP) and the sphincter of Oddi (SO) in patients with alcoholic (ALCP, n = 10), gallstone-associated (GSCP, n = 7), and idiopathic chronic pancreatitis (ICP, n = 21), and in 20 controls. The PP was significantly higher in the patients with ALCP (55.7 +/- 28.9 mm Hg), GSCP (33.6 +/- 16.2 mm Hg), or ICP (44.5 +/- 25.8 mm Hg) than in the controls (16.2 +/- 8.7 mm Hg), but there was no significant difference between ALCP, GSCP, and ICP. There was no significant difference between control subjects and ICP in the motility of SO. In ICP, there was no correlation between the PP and the motility of SO. In ALCP and GSCP, the frequencies of the papillary sphincter waves were significantly higher than in normal subjects, and there were correlations between the PP and the motility of SO. These data suggest that increased pancreatic ductal pressure in GSCP with papillitis or ALCP may be due in part to papillary dysfunction, but not in ICP.

All patients with gallstone ileus admitted to our institutions between 1938 and 1982 were retrospectively analyzed by grouping the patients into 10-year periods. Forty-five patients were studied, of whom 39 required operation. When hospital statistics for admissions, length of stay, and mortality rates from the Mount Sinai Hospital were compared to the gallstone ileus data, it was found that there has been no significant change in the admission rate for these patients. The mortality rate and length of stay of gallstone ileus patients has also remained constant over the past 25 years despite the general hospital decrease in both of these numbers. There has been no change in the complication rate, duration of symptoms prior to admission, or the preoperative diagnostic rate of gallstone ileus during the duration of this study.