sincalide and Sphincter-of-Oddi-Dysfunction

Chronic acalculous gallbladder and chronic acalculous biliary disease are considered functional hepatobiliary diseases. Cholescintigraphy provides physiologic imaging of biliary drainage, making it ideally suited for their noninvasive diagnosis. For chronic acalculous gallbladder disease, calculation of a gallbladder ejection fraction during sincalide cholescintigraphy can confirm the clinical diagnosis and has become a common routine procedure in many nuclear medicine clinics. Published data generally confirm a high overall accuracy for predicting relief of symptoms with cholecystectomy. However, data also exist suggesting it is not useful. The discrepant results probably are caused by the various different methodologies that have been used for sincalide infusion. Proper methodology of sincalide infusion is critical for providing accurate reproducible results, minimizing false positive studies, and preventing adverse side effects. The most common causes for the postcholecystectomy pain syndrome are partial biliary obstruction secondary to stones or tumor and sphincter of Oddi dysfunction. The latter is a partial biliary obstruction at the level of the sphincter. This has long been considered a functional hepatobiliary disease because of the lack of anatomical abnormalities. Sphincterotomy is the present treatment; however, diagnosis requires invasive procedures, such as endoscopic retrograde cholangiopancreatography and sphincter of Oddi manometry, which has a high complication rate and is not widely available. The unique ability of cholescintigraphy to image biliary drainage allows noninvasive diagnosis. Different methodologies have been reported, many with good overall accuracy. Various pharmacologic interventions and quantitative methodologies have been used in conjunction with cholescintigraphy to enhance its diagnostic capability. Further investigations are needed determine the optimal methodology; however, cholescintigraphic methods have already a clinical role in the diagnosis of sphincter of Oddi dysfunction and will be used increasingly in the future.

Topics: Biliary Tract; Biliary Tract Diseases; Chronic Disease; Gallbladder; Gallbladder Diseases; Humans; Radionuclide Imaging; Sincalide; Sphincter of Oddi Dysfunction

To investigate the mechanisms and effects of sphincter of Oddi (SO) motility on cholesterol gallbladder stone formation in guinea pigs.. Thirty-four adult male Hartley guinea pigs were divided randomly into two groups, the control group (n = 10) and the cholesterol gallstone group (n = 24), which was sequentially divided into four subgroups with six guinea pigs each according to time of sacrifice. The guinea pigs in the cholesterol gallstone group were fed a cholesterol lithogenic diet and sacrificed after 3, 6, 9, and 12 wk. SO manometry and recording of myoelectric activity were obtained by a multifunctional physiograph at each stage. Cholecystokinin-A receptor (CCKAR) expression levels in SO smooth muscle were detected by quantitative real-time PCR (qRT-PCR) and serum vasoactive intestinal peptide (VIP), gastrin, and cholecystokinin octapeptide (CCK-8) were detected by enzyme-linked immunosorbent assay at each stage in the process of cholesterol gallstone formation.. The gallstone formation rate was 0%, 0%, 16.7%, and 83.3% in the 3, 6, 9, and 12 wk groups, respectively. The frequency of myoelectric activity in the 9 wk group, the amplitude of myoelectric activity in the 9 and 12 wk groups, and the amplitude and the frequency of SO in the 9 wk group were all significantly decreased compared to the control group. The SO basal pressure and common bile duct pressure increased markedly in the 12 wk group, and the CCKAR expression levels increased in the 6 and 12 wk groups compared to the control group. Serum VIP was elevated significantly in the 9 and 12 wk groups and gastrin decreased significantly in the 3 and 9 wk groups. There was no difference in serum CCK-8 between the groups.. A cholesterol gallstone-causing diet can induce SO dysfunction. The increasing tension of the SO along with its decreasing activity may play an important role in cholesterol gallstone formation. Expression changes of CCKAR in SO smooth muscle and serum VIP and CCK-8 may be important causes of SO dysfunction.

Topics: Animals; Cholesterol; Disease Models, Animal; Electromyography; Enzyme-Linked Immunosorbent Assay; Gallstones; Gastrins; Guinea Pigs; Manometry; Muscle, Smooth; Real-Time Polymerase Chain Reaction; Receptor, Cholecystokinin A; Sincalide; Sphincter of Oddi; Sphincter of Oddi Dysfunction; Vasoactive Intestinal Peptide

The mechanisms that trigger gallbladder evacuation dysfunction, the key risk factor for gallstone formation, have not yet been fully elucidated. The sphincter of Oddi (SO) plays important roles in the regulation of gallbladder evacuation and maintenance of normal hydraulic pressure of the biliary tract. The aim of our study was to investigate the effects of hypercholesterolemia on the motility function of SO and the underlying mechanisms of SO dysfunction (SOD).. Forty New Zealand white rabbits were divided randomly into the control group fed with standard chow and the experimental (Ch) group fed with a high-cholesterol diet for 8 weeks. Changes in the maximal gallbladder emptying rate, gallbladder evacuation with cholecystokinin-octapeptide (CCK-8) stimulation and SO functions of both groups were measured in vivo; B ultrasound examination was used for dynamic observation of peristaltic movements in vivo; SO pressure was measured using manometry; morphological characteristics were observed by electronic microscope; laser scanning confocal fluorescence microscopy was used to identify changes in [Ca]i and Ca oscillation in primary SO smooth muscle cells (SMCs).. Gallbladder cholestasis was observed during early stages of gallstone formation in Ch rabbits. CCK-8 could not improve the gallbladder cholestatic state in Ch group. Passive dilation of SO significantly improved the cholestatic state in Ch rabbits (P<0.05), although the maximal gallbladder emptying rate was still lower than that of the control group. Manometry data indicted a significant increase in the base pressure of the SO low-pressure ampulla segment and high-pressure segment (P<0.05) in Ch group. laser scanning confocal fluorescence microscopy assay data indicated that [Ca]i in SO cells of Ch group significantly increased and were in a state of overload (P<0.05); Ca oscillation signals in SO cells of Ch group were also abnormal.. Hypercholesterolemia initially induced SOD, leading to increased gallbladder evacuation resistance and cholestasis. We suggested that [Ca]i overload and/or Ca oscillation abnormality potentially play important roles in the pathogenesis of SOD.

Topics: Animals; Bile; Calcium Signaling; Cholecystography; Cholestasis; Cholesterol; Cholesterol, Dietary; Disease Models, Animal; Female; Gallbladder Emptying; Hypercholesterolemia; Male; Microscopy, Confocal; Peristalsis; Rabbits; Sincalide; Sphincter of Oddi; Sphincter of Oddi Dysfunction