sincalide and Cholecystitis

Since the early 1980s interventions have been used in conjunction with (99m)Tc-iminodiacetic acid (IDA) radiopharmaceuticals in many different clinical situations, eg, to prepare the patient for the study, to reduce the time of a study, to improve its diagnostic accuracy, and to make diagnoses not otherwise possible. Interventions all have underlying physiological rationales. Some of these interventions are as simple as having the patient fast before the study or eat a meal with high fat content. However, most are pharmacologic interventions, eg, morphine sulfate, cholecystokinin, and phenobarbital. Although these are probably the most common interventions used today, numerous other interventions have been used during the years and likely will be in the future. Interventions have aided in the diagnosis of acute cholecystitis, chronic cholecystitis, biliary obstruction, and sphincter of Oddi dysfunction. This review will discuss in detail the interventions commonly is use today and in somewhat less detail many that have been successfully used on an investigational basis and may have some larger role in the future.

Topics: Biliary Tract Diseases; Cholecystitis; Cholecystitis, Acute; Cholecystokinin; Chronic Disease; Gallbladder Emptying; Humans; Morphine; Radionuclide Imaging; Radiopharmaceuticals; Sincalide; Technetium Tc 99m Diethyl-iminodiacetic Acid

Diagnosis and identification of patients with acalculous biliary pain, who would benefit from surgery, remains a significant clinical problem. The cholecystokinin (CCK) provocation test helps diagnosis, but lack of consistency limits its usefulness.. To characterize the response of gallbladder muscle strips, from patients with acalculous biliary pain, to hormonal and muscarinic stimulation and to compare these with strips from gallstone patients and normal controls.. Eleven patients with acalculous biliary pain were studied, 5 had a positive CCK test. Eight gallbladders from gallstone patients and 6 from partial hepatectomies were used for comparison.. Muscle strips from the body and neck of the gallbladder were suspended in organ baths and dose-response curves were constructed for CCK-8 and carbachol.. In the acalculous group the strips from the body were less sensitive to carbachol than those of the neck.. Since we found no differences in the CCK responses for the groups, it casts doubt over the effectiveness of the CCK test to diagnose acalculous biliary pain. Since carbachol sensitivity was different, it might be that a similar test using muscarinic stimulation would help in the diagnosis of this difficult group of patients.

Topics: Adult; Aged; Carbachol; Cholecystitis; Cholelithiasis; Dose-Response Relationship, Drug; Female; Gallbladder; Humans; In Vitro Techniques; Male; Middle Aged; Muscle Contraction; Muscle, Smooth; Pain; Reference Values; Sensitivity and Specificity; Sincalide; Statistics, Nonparametric

Gallbladder motility was studied by ultrasound in 100 healthy adult volunteers and 150 gallstone patients, in a subgroup of whom gallstone burden, type and number, gallbladder histology and tensiometric responses of gallbladder strips to cholecystokinin octapeptide were evaluated. Patients were divided into contractors (n = 108) and hypocontractors (n = 42), according to their gallbladder motility pattern in vivo. Contractors showed slower gallbladder emptying and increased fasting and postprandial residual volumes, although the ejected amount of bile was greater than that of controls (20.2 +/- SEM 1.1 vs 16.0 +/- 0.7 ml; p < 0.001). In contrast, hypocontractors exhibited slower and less complete gallbladder emptying than controls with a reduction in the absolute amount of ejected bile. Although gallbladder wall inflammation was mild and comparable in specimens from both groups of patients, the thickness of the muscular layer was greater in hypocontractors than in contractors (1073 +/- 76 vs 745 +/- 75 microns, p < 0.01) and related inversely to postprandial ejected volume (r = -0.42; p < 0.03; n = 32) but positively to gallstone volume (r = 0.40; p < 0.03; n = 32). Compared to contractors, gall-bladder muscle strips of hypocontractors exhibited a decrease in frequency and amplitude of spontaneous contraction and in maximal stress and receptor sensitivity to cholecystokinin octapeptide (0.1 nM-1 microM). Postprandial gallbladder evaculation was unaffected by stone number, and by the presence or absence of stone calcification. Gallstone volume was larger in hypocontractors (19.4 +/- 3.0 ml vs 9.6 +/- 0.9 ml, p < 0.001) than contractors. The comparison of in vitro contractility patterns between cholesterol, mixed and pigment stone patients showed a more severe defect in patients with cholesterol and mixed stones than in those with pigment calculi. In conclusion, in gallstone patients: (i) gallbladder motor dysfunction manifests mainly with increased fasting and postprandial residual volumes in contractors and with markedly increased postprandial residual volumes and decreased gallbladder emptying in hypocontractors; (ii) gallbladder kinetics seem to be influenced by stone volume and cholesterol content of calculi but not stone number, calcification or mild chronic cholecystitis; (iii) a form of hypertrophic leiomyopathy is observed in gallstone patients with the most impaired gallbladder motor function.

Topics: Adult; Aged; Cholecystitis; Cholelithiasis; Cholesterol; Female; Gallbladder; Humans; Male; Middle Aged; Muscle Contraction; Muscle, Smooth; Sincalide; Ultrasonography

The pathogenesis of acute cholecystitis (AC) is controversial. Bile acids may be involved in the pathogenesis of AC because the hydrophobic chenodeoxycholic acid (CDCA) reproduced in vitro the muscle dysfunction observed in AC and was prevented by the hydrophilic ursodeoxycholic acid (UDCA). The present study examined the in vivo effects of UDCA or CDCA on gallbladder muscle dysfunction caused by AC. Guinea pigs were treated with placebo, UDCA, or CDCA for 2 weeks before sham operation or induction of AC by bile duct ligation (BDL) for 3 days. Pretreatment with oral UDCA prevented the defective contraction in response to agonists (acetylcholine [ACh], cholecystokinin 8 [CCK-8], and KCl) that occurs after BDL. Prostaglandin (PG) E(2)-induced contraction remained normal in the placebo and UDCA-treated groups but was impaired in the CDCA-treated group. Treatment with UDCA also prevented the expected increase in the levels of H(2)O(2), lipid peroxidation, and PGE(2) content in the placebo-treated AC group, whereas CDCA caused further increases in these oxidative stress markers. The binding capacity of PGE(2) to its receptors and the activity of catalase were reduced after treatment with CDCA. Treatment with UDCA enriched gallbladder bile acids with its conjugates and reduced the percentage of CDCA conjugates. In contrast, treatment with CDCA significantly decreased the percentage of UDCA in bile. In conclusion, oral treatment with UDCA prevents gallbladder muscle damage caused by BDL, whereas oral treatment with CDCA worsens the defective muscle contractility and the oxidative stress.

Topics: Acetylcholine; Acute Disease; Animals; Bile; Bile Acids and Salts; Bile Ducts; Biomarkers; Catalase; Chenodeoxycholic Acid; Cholecystitis; Dinoprostone; Gallbladder; Guinea Pigs; Hydrogen Peroxide; Ligation; Lipid Peroxides; Muscle Contraction; Muscle, Smooth; Oxidative Stress; Receptors, Prostaglandin E; Sincalide; Ursodeoxycholic Acid

Muscle strips from experimental acute cholecystitis (AC) exhibit a defective contraction. The mechanisms responsible for this impaired contraction are not known. The present studies investigated the nature of these abnormalities. AC was induced by ligating the common bile duct of guinea pigs for 3 days. Contraction was studied in enzymatic dissociated muscle cells. Cholecystokinin (CCK) and prostaglandin E2 (PGE2) receptor binding studies were performed by radioreceptor assay. The levels of lipid peroxidation, cholesterol, phospholipid, and H2O2 as well as the catalase and superoxide dismutase (SOD) activities were determined. PGE2 content was measured by radioimmunoassay. Muscle contraction induced by CCK, ACh, or KCl was significantly reduced in AC, but PGE2-induced contraction remained normal. GTPgammaS, diacyglycerol (DAG), and 1,4,5-trisphosphate (IP3), which bypass the plasma membrane, caused a normal contraction in AC. The number of functional receptors for CCK was significantly decreased, whereas those for PGE2 remained unchanged in AC. There was a reduction in the phospholipid content and increase in the level of lipid peroxidation as well as H2O2 content in the plasma membrane in AC. The PGE2 content and the activities of catalase and SOD were also elevated. These data suggest that AC cause damage to the constituents of the plasma membrane of muscle cells. The preservation of the PGE2 receptors may be the result of muscle cytoprotection.

Topics: Acetylcholine; Acute Disease; Animals; Catalase; Cells, Cultured; Cholecystitis; Cholesterol; Dinoprostone; Gallbladder; Guinea Pigs; Lipid Peroxidation; Muscle Contraction; Muscle, Smooth; Phospholipids; Potassium Chloride; Sincalide; Superoxide Dismutase

Morphine sulfate causes spasm of the sphincter of Oddi. Conversely, the cholecystagogue sincalide produces relaxation of the sphincter and contraction of the gallbladder. This prospective study evaluated whether sincalide could produce normal gallbladder emptying after low-dose morphine sulfate (0.04 mg/kg).. Thirty to 120 minutes (mean, 51 minutes) after morphine sulfate-augmented gallbladder visualization, 25 gallbladder ejection fractions in 24 patients were measured. One patient was studied twice, 2 weeks apart. Gallbladder ejection fractions were calculated after controlled 30-minute infusions of sincalide (0.02 microg/kg).. Fourteen gallbladder ejection fractions were normal (mean, 63%; range, 45% to 80%) and 11 gallbladder ejection fractions were abnormal (mean, 12%; range, 5% to 19%; P < 0.001).. Normal gallbladder ejection fractions can be obtained as early as 30 minutes after administration of low-dose morphine sulfate. Potential applications of post-morphine sulfate sincalide challenge would include, for example, to support true-negative morphine sulfate-augmented gallbladder visualization in a patient with a high clinically indicated potential of having acute cholecystitis.

Topics: Adult; Cholecystitis; Female; Gallbladder; Gallbladder Emptying; Gastrointestinal Agents; Humans; Male; Middle Aged; Morphine; Prospective Studies; Radionuclide Imaging; Sincalide; Time Factors

Numerous publications have reported that a low gallbladder ejection fraction (GBEF) determined by cholecystokinin (CCK) cholescintigraphy has a high positive predictive value for the diagnosis of chronic acalculous cholecystitis (CAC). Clinicians and surgeons have found this test to be clinically useful as an objective method to confirm their clinical diagnosis. However, an abnormally low GBEF is not specific for CAC. For example, numerous other diseases have been associated with a low GBEF, and various therapeutic drugs can cause poor gallbladder contraction. Importantly, improper CCK infusion methodology can result in an erroneously low GBEF. More than one third of healthy subjects and patients who receive sincalide, 0.02 microg/kg infused over 1-3 min, will have an erroneously low GBEF but will have a normal GBEF with a slower infusion (30-60 min) of the same total dose. Because of enthusiastic acceptance of CCK cholescintigraphy by clinicians, the types of patients referred for this test have changed over time. Patients investigated in publications confirming the usefulness of CCK cholescintigraphy had a high pretest likelihood of disease. They underwent extensive workup to rule out other diseases and were followed up for months or years before CCK cholescintigraphy was performed, allowing other diseases to become manifest or symptoms to resolve. However, CCK cholescintigraphy is now being used by clinicians to shorten the workup and follow-up time based on the rationale that CCK cholescintigraphy can quickly confirm or exclude the diagnosis. This new group of referral patients has a lower likelihood of the disease. Many will ultimately be diagnosed with diseases other than CAC. The positive predictive value of this test will likely be lower and the false-positive rate will likely be higher. Nuclear medicine physicians must work to minimize false-positive studies to maintain the confidence of referring clinicians. First, we can educate referring physicians as to the proper use of this study. Next, we must perform CCK cholescintigraphy using optimal methodology that will result in the lowest possible false-positive rate. And finally, we must interpret CCK cholescintigraphy in light of the patient's history, prior workup and clinical setting.

Topics: Cholecystitis; Cholecystokinin; Chronic Disease; False Positive Reactions; Female; Gallbladder; Gallbladder Emptying; Humans; Male; Radionuclide Imaging; Sincalide

Topics: Adult; Cholecystectomy; Cholecystitis; Female; Follow-Up Studies; Gallbladder; Gastrointestinal Agents; Humans; Male; Sensitivity and Specificity; Sincalide; Ultrasonography

Recent data and reanalysis of the literature suggest that nonvisualization of the gallbladder on the delayed images of cholescintigraphy is a nonspecific finding. Morphine augmentation has a reasonably good, though imperfect, specificity and positive predictive value, that are significantly better than for delayed imaging, in addition to its logistical advantage (shortening the imaging time). The technique is recommended, therefore, for routine clinical use in patients with nonvisualization of the gallbladder at 1 hr. Further study seems to be necessary to assess the effect of variable or no visible effect of low-dose morphine among patients on the efficacy of morphine-augmented cholescintigraphy. Sincalide pretreatment, when administered at the physiologic rate, is helpful in conditions in which functional resistance to tracer flow into the gallbladder are present. The results from the series by Chen et al. and by Kim et al. suggest that morphine augmentation can further improve the efficacy of the test even after CCK pretreatment. A comparison between the efficacy of delayed imaging and that of imaging for 60-90 min after CCK pretreatment is not available. Therefore, the latter does not obviate the need for delayed imaging when the morphine augmentation technique is not used. Finally, the nuclear medicine physician should use the most optimal technique for the pharmacologic intervention, in other words, the dose and the rate of administration. Certain conditions and medications may affect gallbladder contraction. It is also important to be aware of the various physiologic and pharmacologic effects on imaging findings, not only those findings that are normal but also the undesirable variants. Failure to recognize such effects can lead to incorrect interpretations.

Topics: Acute Disease; Cholecystitis; Cholecystokinin; Cystic Duct; Gallbladder Emptying; Humans; Morphine; Radionuclide Imaging; Sincalide

To evaluate the measurement with ultrasonography (US) of the gallbladder ejection fraction after slow-infusion cholecystokinin stimulation in patients with biliary symptoms and in individuals without symptoms.. Gallbladder volumes were calculated in 60 healthy volunteers after a 30-minute infusion of sincalide. The time to maximum response, the gallbladder ejection fraction, and the rate of initial contraction were obtained at US. A total of 100 symptomatic patients were evaluated with this technique. Reference standards included surgical outcome or results of clinical follow-up of at least 1 year.. The average ejection fraction +/- 2 standard deviations was 80% +/- 30. A fraction greater than 60% was considered to be a normal response to cholecystokinin stimulation. There was no statistically significant sex difference. Slow infusion did not produce any side effects. A sensitivity of 75% and a specificity of 100% for determination of gallbladder ejection fraction at US were obtained in patients with surgical and histopathologic proof of disease.. The slow-infusion method is reliable, safe, and reproducible in evaluating gallbladder contraction. The cholecystokinin-stimulated gallbladder ejection fraction test may be useful in determining which patients could benefit from surgery.

Topics: Adult; Aged; Aged, 80 and over; Case-Control Studies; Cholecystitis; Cholelithiasis; Female; Follow-Up Studies; Gallbladder Emptying; Humans; Infusions, Intravenous; Male; Middle Aged; Reproducibility of Results; Sensitivity and Specificity; Sincalide; Ultrasonography

We retrospectively reviewed the medical records of 107 patients in two community hospitals who had undergone cholecystokinin-stimulated cholescintigraphy with ejection fraction to determine whether this test is reliable in identifying patients whose symptoms will improve following cholecystectomy. Patients with cholelithiasis or incomplete medical records and patients who could not be interviewed were excluded from the study. Forty-two of 58 study patients (72%) had an abnormal ejection fraction (defined as 35% or less); 27 of 42 patients (64%) underwent cholecystectomy. Twenty-six of 27 (96%) reported lessening of or resolution of symptoms following cholecystectomy. Sixty-seven per cent of the surgical specimens from the 27 patients demonstrated chronic cholecystitis. Fifteen of 42 patients (36%) with abnormal ejection fractions did not undergo cholecystectomy; 12 of 15 (80%) also reported lessening or resolution of symptoms. Of the 16 of 58 patients with a normal ejection fraction, 2 underwent cholecystectomy and reported resolution of symptoms. Five of 14 (36%) with normal ejection fractions who did not undergo cholecystectomy reported improvement. In this series, most patients with an abnormal ejection fraction had lessening of symptoms regardless of whether they underwent cholecystectomy.

Topics: Adult; Aniline Compounds; Case-Control Studies; Cholecystectomy; Cholecystitis; Chronic Disease; Female; Gallbladder; Gallbladder Emptying; Glycine; Humans; Imino Acids; Logistic Models; Male; Middle Aged; Organotechnetium Compounds; Predictive Value of Tests; Radionuclide Imaging; Radiopharmaceuticals; Retrospective Studies; Sincalide

It is becoming increasingly evident from a number of studies that endoscopic ultrasound (EUS) is much more sensitive in the diagnosis of cholecystitis than transabdominal ultrasound (TUS). The present study was undertaken to further evaluate this relative sensitivity.. Sixty-six patients with biliary-type pain and a negative transabdominal ultrasound examination underwent combined endoscopic ultrasound and stimulated biliary drainage (EUS/SBD). Stimulated biliary drainage was obtained following intraduodenal infusion of magnesium sulfate or intravenous sincalide, a CCK analogue. EUS was considered positive if sludge or small stones were seen in the gallbladder. Stimulated biliary drainage was considered positive if calcium bilirubinate granules or cholesterol crystals were seen on microscopic examination of aspirated bile.. At operation, 61 of the patients had cholecystitis documented histologically. Fifty-eight of the patients had gallbladder sludge or small stones on EUS. One patient had a negative EUS, but had calcium bilirubinate granules in the bile. Twenty-one patients were followed post-operatively for a period of seven to 17 months, with an average of 10.5 months. Nineteen patients (90.5%) remain free of biliary pain.. Combined endoscopic ultrasound and stimulated biliary drainage (EUS/SBD) had a high sensitivity of 92.4% and a positive predictive value of 100% in the diagnosis of cholecystitis when transabdominal ultrasound was negative. A significant majority (90.5%) of patients with positive EUS/SBD who underwent cholecystectomy had resolution of their biliary pain.

Topics: Cathartics; Cholecystectomy; Cholecystitis; Cholelithiasis; Diagnosis, Differential; Duodenoscopy; Follow-Up Studies; Gallbladder Emptying; Gastrointestinal Agents; Humans; Magnesium Sulfate; Sensitivity and Specificity; Sincalide; Treatment Outcome; Ultrasonography

Strips from human gallbladder removed at surgery were exposed to cholecystokinin octopeptide CCK-OP 15 nM and were subjected to electrical field stimulation (EFS) in vitro using parameters for selective stimulation of nerves (5- to 10-sec trains of 0.3-msec pulses at 10 Hz). An adjacent strip from the same specimen was processed for histological examination. These preparations were given a numerical score for inflammatory change. The strength of contraction in response to CCK-OP was inversely related to the severity of inflammation. Gallbladders with no response to EFS had a higher inflammation score (median 11, range 5-16) than those with a response (median 7, range 3-12). We conclude that inflammatory changes in human gallbladder impair responses to neural and hormonal stimulation, but we are unable to determine unequivocally in this study whether this is a result of damage to nerves or muscle cells. However, the observation that some strips were able to contract in response to CCK-OP but not to neural stimulation suggests the possibility of neural damage in gallbladder inflammation.

Topics: Cholecystitis; Electric Stimulation; Gallbladder; Gallbladder Emptying; Humans; In Vitro Techniques; Muscle Contraction; Muscle, Smooth; Sincalide

Cholecystokinin hepatobiliary (CCK-HIDA) scintigraphy is used to triage patients with chronic abdominal pain and suspected gall-bladder dysfunction. This study evaluates the predictive value of CCK-HIDA for clinical outcome after surgical and medical therapy. Fifty-six patients (45 females), mean age 43 +/- 9 years, with otherwise normal investigations, including normal ultrasound, fasted for more than 8h and then had 70MBq technetium-99m-EHIDA injected. One and a half hours later 15 ng/kg CCK was infused over 45 min. Seventy minutes dynamic imaging commenced 5 min prior to infusion. An abnormal gall-bladder ejection fraction (GBEF) was defined as < 50%. Patients were treated medically, or by cholecystectomy, depending on the surgeon's overall assessment, including results of the CCK-HIDA study. Patient status was then obtained in 51/56 patients at least 3 months after the scan or at least 1 month after surgery. All surgical specimens were reviewed independently for pathological changes of chronic acalculous cholecystitis. Of the 11 patients with an abnormal gall-bladder ejection fraction, nine (82%) underwent cholecystectomy, all of whom achieved total symptomatic cure, while two patients underwent other therapy, both of whom remained symptomatically unchanged. Of the 40 patients whose gall-bladder ejection fraction was normal, only five (12.5%) underwent cholecystectomy, of whom four were cured and one partially improved at follow up. Of the 35 patients with a normal gall-bladder ejection fraction and who underwent forms of therapy other than cholecystectomy, nine were cured symptomatically, 13 improved, 10 remained unchanged and three were symptomatically worse at follow up.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Cholecystectomy; Cholecystitis; Female; Follow-Up Studies; Gallbladder; Gallbladder Emptying; Humans; Imino Acids; Male; Organotechnetium Compounds; Predictive Value of Tests; Radionuclide Imaging; Sensitivity and Specificity; Sincalide; Technetium Tc 99m Diethyl-iminodiacetic Acid

Thirty patients with chronic upper abdominal pain and no evidence of cholelithiasis were entered into this study. All had negative ultrasonography of the gallbladder, and most had a host of other negative investigations. These patients were referred to a surgeon to evaluate the possibility of atypical biliary colic associated with chronic acalculous cholecystitis. All patients underwent cholecystokinin-stimulated cholescintigraphy and were offered cholecystectomy if the ejection fraction was less than 35 per cent. Of the 30 patients, 27 (90%) had pathologically abnormal gallbladders. Follow-up averaged over 1 year (13.2 mo), and relief of symptoms occurred in 28 (94%). The authors conclude that in appropriately selected patients with symptoms of biliary colic (typical or atypical) and no evidence of cholelithiasis, a cholecystokinin-stimulated cholescintigram is a significant help in predicting not only which patients have gallbladder disease, but also how likely cholecystectomy is to result in an improvement in their symptoms.

Topics: Adolescent; Adult; Cholecystectomy; Cholecystitis; Cholecystography; Cholelithiasis; Chronic Disease; Diagnosis, Differential; Female; Humans; Male; Middle Aged; Pain; Radionuclide Imaging; Sincalide

It has been postulated that cholecystokinin sonography may be useful in the diagnosis of acute acalculous cholecystitis in the hospitalized patient. To evaluate this hypothesis, sincalide, a cholecystokinin derivative, was administered to 15 fasting trauma patients who had undergone laparotomy. No biliary or gallbladder disease was found in any patient. Sincalide was slowly administered intravenously, and the gallbladder was examined with ultrasound every 5 minutes for 60 minutes. The average decreases in length, height, and width of the gallbladder were 15%, 23%, and 21%, respectively. In only four of the 15 patients was there a decrease by more than 50% in any of these dimensions. The average decrease in gallbladder volume was 33% (range, 0%-97%), with no change in gallbladder volume in four patients. There is considerable variability in gallbladder response to administration of sincalide in the fasting hospitalized patient. Lack of contraction of the gallbladder after injection of cholecystokinin should not be considered a major criterion in the diagnosis of acute acalculous cholecystitis.

Topics: Acute Disease; Adolescent; Adult; Cholecystitis; Cholelithiasis; Female; Gallbladder; Humans; Male; Middle Aged; Sincalide; Ultrasonography

Biliary scintigraphy and ultrasound imaging were performed in 52 patients with suspected biliary tract pathology. Results were correlated with the findings of direct cholangiography. Several new innovations in scintigraphic technique were used. The combination of ultrasound imaging and scintigraphy correctly identified biliary tract obstruction in 17 of 19 patients, 12 of whom had dilated bile ducts on ultrasonography. Intrahepatic cholestasis was correctly diagnosed in 11 of 13 patients. Accurate discrimination between intrahepatic and extrahepatic cholestasis was achieved in 28 of 32 patients (88%) with the combined studies. Scintigraphy also provided a correct diagnosis of acute cholecystitis in all 9 patients with surgically confirmed disease. Eleven additional patients with gallbladder or pancreatic disease had normal bile ducts at scintigraphy, which was confirmed with cholangiography. When combined with ultrasound imaging, modern biliary scintigraphy can (a) provide excellent discrimination between intrahepatic and extrahepatic cholestasis and (b) help determine the need for subsequent invasive diagnostic studies in selected patients.

Topics: Adult; Aged; Biliary Tract; Cholangiography; Cholecystitis; Cholestasis, Extrahepatic; Cholestasis, Intrahepatic; Common Bile Duct Diseases; Female; Gallbladder Diseases; Humans; Imino Acids; Male; Middle Aged; Pancreatic Diseases; Prospective Studies; Radionuclide Imaging; Sincalide; Technetium; Technetium Tc 99m Disofenin; Ultrasonography

To determine the sites and mechanisms of action of cholecystokinin-octapeptide (CCK-OP) on the human gallbladder, effects of atropine sulfate on CCK-OP-evoked contractions were studied in both in vivo and in vitro experiments. In vivo studies performed by means of real time ultrasonography in six healthy volunteers showed remarkable contractions of the gallbladder after intramuscular injection of CCK-OP (0.07 microgram/kg), which was nearly abolished by premedication of atropine sulfate (0.015 mg/kg). Atropine sulfate (10(-6) M) slightly but significantly reduced CCK-OP (10(-11) M-3 X 10(-7) M) induced contractions and the dose-response curve for CCK-OP was shifted to the right of the muscle strips of the human gallbladders. It is suggested that CCK-OP acts mainly on cholinergic neurons in vivo. On the contrary, the most sensitive sites of action of CCK-OP might be smooth muscles rather than cholinergic neurons in vitro.

Topics: Adult; Atropine; Ceruletide; Cholecystitis; Dose-Response Relationship, Drug; Egg Yolk; Gallbladder; Humans; In Vitro Techniques; Male; Muscle Contraction; Sincalide; Ultrasonography

Hepatobiliary studies were performed over a three-year period on 139 patients suspected of having cystic duct obstruction. Each patient was infused intravenously with sincalide, a C-terminal octapeptide of CCK, 15 minutes prior to the administration of the hepatobiliary imaging agent Tc-99m paraisopropyl iminodiacetic acid (PIPIDA). Analysis of the results demonstrated significant advantages in pretreating patients with sincalide in hepatobiliary studies in a small facility with a relatively large patient load. Most of our studies were completed within 2 hours without jeopardizing the sensitivity (97%) or accuracy (96%) of the test. The specificity (88%) was comparable to percentages reported by others. Most investigators have reported that chronic cholecystitis contributed to the majority of false-positive cases. In addition, inconsistency in the documentation of criteria for the determination of acute cholecystitis (surgical, radiologic, or histologic also could be a cause for such a discrepancy. Knowledge of some important variables may help improve the specificity of the test: an awareness of the following factors during scan interpretation: 1) the effectiveness of the sincalide pretreatment dose, 2) the patient's pretest status (fasting or nonfasting, postanalgesic medication or no analgesics), and 3) time limit for gallbladder visualization. With these variables in mind, the hepatobiliary imaging using pretreatment with sincalide is proven to be a practical procedure protocol with good sensitivity and accuracy as well as specificity.

Topics: Bile Duct Diseases; Cholecystitis; Cystic Duct; Humans; Imino Acids; Organotechnetium Compounds; Premedication; Radionuclide Imaging; Sincalide; Technetium; Time Factors

A retrospective review was made of all radionuclide hepatobiliary studies performed in a major trauma center over a 27-month period and correlated with the patients' clinical course. In a population of 42 patients (27 of whom were on total parenteral nutrition [TPN]) who had severe intercurrent illness (primarily trauma), and an additional 18 patients who had hepatocellular dysfunction, hepatobiliary imaging confirmed a patent cystic duct in 43 of 60 patients (72%). Fourteen of these 43 patients (33%) had gallbladder visualization at later than one hour after radiotracer administration, and seven of these 14 required imaging from four to 24 hours. Of 17 patients who had nonvisualization of the gallbladder, four had surgically proved acute cholecystitis. Images of nine of the remaining 13 patients with gallbladder nonvisualization were not obtained for 24 hours. The presence of gallstones, wall thickening, or sludge on sonograms did not correlate with cystic duct patency, and was not specific for acute cholecystitis. Though gallbladder function is compromised in the population with severe intercurrent disease, radionuclide hepatobiliary imaging is still valuable; it can confirm a patent cystic duct in at least 72% of patients if routine imaging is continued for up to 24 hours.

Topics: Acute Disease; Cholecystitis; Diagnosis, Differential; Diagnostic Tests, Routine; Gallbladder; Hepatitis, Alcoholic; Hepatitis, Chronic; Humans; Imino Acids; Intestine, Small; Liver; Organotechnetium Compounds; Parenteral Nutrition, Total; Radionuclide Imaging; Respiratory Distress Syndrome; Retrospective Studies; Sincalide; Technetium; Technetium Tc 99m Disofenin; Time Factors; Ultrasonography; Wounds and Injuries

A review of gallbladder scintigraphy in patients with potentially compromised hepatobiliary function revealed two groups in whom cholecystitis might be mistakenly diagnosed. In 200 consecutive hospitalized patients studied with technetium-99m-PIPIDA for acute cholecystitis or cholestasis, there were 41 alcoholics and 17 patients on total parenteral nutrition. In 60% of the alcoholics and 92% of those on parenteral nutrition, absent or delayed visualization of the gallbladder occurred without physical or clinical evidence of cholecystitis. A cholecystagogue, sincalide, did not prevent the false-positive features which presumably are due to altered bile flow kinetics related to alcoholism and parenteral nutrition. Four patients on parenteral nutrition undergoing cholecystectomy for suspected cholecystitis had normal gallbladders filled with jellylike viscous thick bile. A positive (nonvisualized or delayed visualized) gallbladder PIPIDA scintigram in these two populations should not be interpreted as indicating a need for cholecystectomy.

Topics: Alcoholism; Bile; Cholecystitis; Cholecystokinin; Cholestasis; False Positive Reactions; Gallbladder; Humans; Imino Acids; Organotechnetium Compounds; Parenteral Nutrition; Parenteral Nutrition, Total; Peptide Fragments; Radionuclide Imaging; Sincalide; Technetium

Cholecystokinin (CCK) and its C-terminal octapeptide analog, Sincalide, have been utilized in two separate roles for the evaluation of gallbladder disease. These are: (1) prior to cholescintigraphy to evacuate the gallbladder and optimized subsequent filling with radiotracers, and (2) to study contractile function of visualizing gallbladders on cholecystography and cholescintigraphy. As a preparation for 99mTc-IDA studies, it clearly facilitates earlier gallbladder filling in patients with chronic cholecystitis, thereby ruling out complete cystic duct obstruction. The problem lies in the fact that the use of CCK as a premedication markedly decreases the sensitivity of the study to detect chronic cholecystitis, since the findings become indistinguishable from patients with normal gallbladders. For this reason, the authors prefer to obtain delayed images, since chronic cholecystitis is frequently associated with gallbladder filling beyond the first hour. The role of CCK in detecting abnormal gallbladder function in the normally visualizing gallbladder also is controversial. Other studies as well as the author's experience suggests that as much as one-forth of positive cases may be associated with normal gallbladders at surgery and often even on microscopic examination. However, most importantly, the great majority of these patients are relieved of their symptoms following surgery. It appears reasonable that CCK or Sincalide cholecystography or cholescintigraphy may be detecting functional abnormalities before anatomic changes occur and can, therefore, serve as a useful examination in selecting symptomatic patients who may benefit from cholecystectomy.

Topics: Acute Disease; Cholecystectomy; Cholecystitis; Cholecystography; Cholecystokinin; Common Bile Duct; Gallbladder; Humans; Imino Acids; Injections, Intravenous; Muscle Contraction; Muscle, Smooth; Peptide Fragments; Radionuclide Imaging; Sincalide; Technetium; Technetium Tc 99m Diethyl-iminodiacetic Acid