Cholecystokinin Cholescintigraphy Research Articles

Kinetics of Gallbladder Emptying During Cholecystokinin Cholescintigraphy as an Indicator of In Vivo Hormonal Sensitivity.

Cholecystokinin cholescintigraphy is used clinically to quantify gallbladder ejection fraction as an indicator of functional gallbladder disorder. It can also provide the opportunity to quantify an individual's responsiveness to the physiologic stimulant of gallbladder contraction, cholecystokinin, which is a major regulator of appetite and postprandial satiety. Methods: In the current work, we use cholecystokinin cholescintigraphy to quantify the kinetics of gallbladder emptying, including average and peak rates, in response to a standard cholecystokinin infusion. Results: We demonstrated that patients with no gallstones or biliary obstruction who empty their gallbladders completely in response to cholecystokinin, having an ejection fraction greater than 80%, exhibit a broad range of sensitivity to this hormone. Three distinct kinetic profiles were observed, with those most sensitive to cholecystokinin achieving the earliest peak and the fastest rate of gallbladder emptying, whereas those least sensitive to cholecystokinin have the latest peak and the slowest rate of emptying. Conclusion: Patients can have abnormal cholecystokinin stimulus-activity coupling as an effect of endogenous negative allosteric modulation by membrane cholesterol. This was predicted in ex vivo studies but has not, to our knowledge, previously been demonstrated in vivo. This type of kinetic analysis provides a tool to quantify cholecystokinin responsiveness in patients and identify patients who might benefit from a drug that would positively modulate cholecystokinin action to improve their appetite regulation and to better control their weight.

Current Standard Technique for Cholecystokinin Cholescintigraphy

Current Standard Technique for Cholecystokinin CholescintigraphyMark Tulchinsky, Harvey A. Ziessman and Alan H. MaurerAudio Available | Share

T1625 Is Pain Provocation With Cholecystokinin Administration on Cholescintigraphy Predictive of Relief of Symptoms for Biliary Dyskinesia Following Cholecystectomy?

Introduction Biliary dyskinesia, also referred to as chronic acalculous gallbladder disease (CAGD), falls within the spectrum of diseases associated with gallbladder dysmotility. Cholecystokinin cholescintigraphy (CCK-CS) has been used to evaluate for CAGD, with a gallbladder ejection fraction (GBEF) of <35% being indicative of gallbladder dysfunction. The reproduction of biliary colic upon administration of CCK has been cited as indicative of CAGD. Our purpose was to determine if reproduction of pain during CCK-CS is a predictor of surgical outcomes or as a correlate to pathology. Methods A retrospective review of patients was performed to evaluate adults with a diagnosis of CAGD who underwent CCK-CS prior to surgical intervention. CPT and ICD-9 coding queries were used to identify the patient population. Patients with cholelithiasis were excluded. This study was approved by the institutional Human Assurances Committee. Results 64 patients met inclusion criteria. Two patients were lost to follow up and were excluded. During CCK administration, 41 patients (66.13%) reported symptoms similar to their presenting complaint. 21 patients reported no symptoms with CCK administration. Pathology review demonstrated either normal histology (n=4), cholesterolosis (n=4), chronic cholecystitis (n=47), both cholesterolosis and chronic cholecystitis (n=6), or autolysis (n=1). There was no significant relationship between pathology and either GBEF or reproduction of symptoms with CCK administration. 81% of patients (n=50) had relief of symptoms following cholecystectomy (mean EF of 19.55% ± 12.16%). 33 of these patients (66.00%) had reproduction of symptoms with CCK-CS. Twelve patients had recurrence of symptoms (mean EF of 17.18% ± 7.59%) despite surgery. Eight of these patients (66.67%) had symptom reproduction with CCK administration. There was no significant correlation with either the EF or reproduction of symptoms following CCK administration as a predictor of postoperative outcome on assessment by unpaired Student's t-test. Conclusion Provocation of pain CCK-CS is an unreliable indicator of postoperative relief of symptoms than GBEF.

Long-Term Evaluation of Biliary Dyskinesia in Pediatrics

Purpose: Biliary dyskinesia, a motility disorder of the gallbladder, causes poor emptying and pain. Quantitative cholecystokinin cholescintigraphy (QCC) identifies patients with abnormal gallbladder emptying. Ten patients (8 female, 2 male, mean age 13.8 y) with chronic right upper quadrant pain were evaluated for biliary dyskinesia using QCC. Abdominal complaints were present for a mean of 13.6 months. Epigastric pain, nausea and vomiting, food intolerance and diarrhea and/or constipation were also reported. Methods: Abdominal ultrasound, upper GI series and abdominal CT scan were done. Abnormal gallbladder ejection fractions after cholecystokinin were defined as less than 35% excretion. Results: Nine patients had normal endoscopies with one showing histological evidence of esophagitis. All patients had normal liver function. None of the patients had Helicobacter pylori. The average gallbladder ejection fraction in this group of patients was 16.97%. All 10 patients had a laparoscopic cholecystectomy and histology showed mild chronic cholycystitis in 8 of 10 patients; two had normal gallbladders. Gallstones were found surgically in 2 patients that had normal imaging studies. The mean follow up period following surgery was 23.8 months. The four patients with significant right upper quadrant pain before surgery had complete resolution of their abdominal symptoms following cholecystectomy with no other significant gastrointestinal complaints. The six patients who had continuing abdominal complaints following surgery reported right upper quadrant pain in addition to a combination of epigastric pain, vomiting and or constipation/diarrhea before surgery. Conclusions: (1) Cholecystectomy may not relieve all abdominal complaints in documented cases of biliary dyskinesia. (2) Cases of biliary dyskinesia with abdominal complaints confined to the right upper quadrant are more likely to respond to cholecystectomy. (3) Cases of biliary dyskinesia with multifocal abdominal complaints are less likely to respond completely to cholecystectomy. (4) Biliary dyskinesia may be part of a more global motility disturbance.

Functional Gallbladder and Sphincter of Oddi Disorders

The functional disorder of the gallbladder (GB) is a motility disorder caused initially either by metabolic abnormalities or by a primary motility alteration. The functional disorders of the sphincter of Oddi (SO) encompass motor abnormalities of either the biliary or the pancreatic SO. Dysfunction of the GB and/or biliary SO produce similar patterns of pain. The pain caused by a dysfunction of the pancreatic SO can be similar to that of acute pancreatitis. The symptom-based diagnostic criteria of motility dysfunction of the GB and biliary SO are episodes of moderate to severe steady pain located in the epigastrium and right upper abdominal quadrant that last at least 30 minutes. GB motility disorder is suspected after gallstones and other structural abnormalities have been excluded. This diagnosis should then be confirmed by a decreased GB ejection fraction induced by cholecystokinin at cholescintigraphy and after disappearance of the recurrent biliary pain after cholecystectomy. Symptoms of biliary SO dysfunction may be accompanied by features of transient biliary obstruction, and those of pancreatic SO dysfunction are associated with elevation of pancreatic enzymes and even pancreatitis. Biliary-type SO dysfunction is more frequently recognized in postcholecystectomy patients. SO manometry is valuable to select patients with sphincter dysfunction; however, because of the high incidence of complications, these patients should be referred to an expert unit for such assessment. Thus invasive tests should be performed only in the presence of compelling clinical evidence and after noninvasive testing has yielded negative findings. The committee recommends that division of the biliary or pancreatic sphincters only be considered when the patient has severe symptoms, meets the required criteria, and other diagnoses are excluded.

Controversies Concerning Pathophysiology and Management of Acalculous Biliary-Type Abdominal Pain

Acalculous biliary-type abdominal pain is a commonly encountered clinical problem whose pathophysiology is unclear and evaluation and management are controversial. Cholecystokinin cholescintigraphy to measure the gallbladder ejection fraction (GEF) has been advocated as a criterion for cholecystectomy. However, there is no consensus regarding the dose and rate of infusion of cholecystokinin, both of which can alter the GEF, and the definition of an abnormal ejection fraction varies among studies. Many but not all studies have concluded that a low GEF predicts good outcomes after cholecystectomy, but most studies suffer from poor methodology and there is only one prospective randomized controlled trial. Also, some patients with a normal GEF have responded to cholecystectomy. Another controversial area has been the role of sphincter of Oddi dysfunction (SOD) in patients with biliary-type pain and gallbladder in situ. Some reports suggest an overlap between SOD and low GEF, although a causal relationship has not been established. Yet another subject of interest is the role of visceral hyperalgesia in patients with acalculous biliary-type pain. We have reviewed the relevant literature relating to these issues and have highlighted the controversial aspects. In the absence of high-quality studies, an evidence-based treatment algorithm is difficult to design but will be proposed. More prospective controlled trials are warranted to better define the appropriate evaluation and management of patients with this syndrome.

Systematic review and meta-analysis: does gall-bladder ejection fraction on cholecystokinin cholescintigraphy predict outcome after cholecystectomy in suspected functional biliary pain?

Patients with suspected functional biliary pain often undergo cholecystectomy if a decreased gall-bladder ejection fraction (GBEF <35%) is demonstrated by cholecystokinin cholescintigraphy. However, the validity of GBEF in predicting which patients will have symptomatic relief following cholecystectomy is unclear. To determine whether patients with suspected functional biliary pain with decreased GBEF have a better symptomatic outcome after cholecystectomy than those with normal GBEF. Systematic review and meta-analysis of the published literature through MEDLINE and EMBASE databases. We included nine studies with a total of 974 patients with suspected functional biliary pain; 362 patients underwent cholecystectomy. Most studies assessed outcome by direct patient interview. Mean ages across the studies ranged from 35 to 47 years; 78% of all patients were female. Mean duration of follow-up after surgery ranged from 1 to 2.5 years. After cholecystectomy, 94% of the patients with reduced GBEF had a positive outcome compared to 85% among those with normal GBEF. The pooled Mantel-Haenszel odds ratio for positive outcome was 1.37 (95% confidence interval 0.56-3.34), P=0.56. These data do not support the use of GBEF to select patients with suspected functional biliary pain for cholecystectomy. Prospective randomized trials are required if this practice is to be evidence-based.

Chronic Acalculous Biliary Disease: Cholecystokinin Cholescintigraphy is Useful in Formulating Treatment Strategy and Predicting Success after Cholecystectomy

Patients with symptoms consistent with biliary colic who do not demonstrate calculi on routine sonography present a diagnostic dilemma for clinicians. For those patients in whom other disease entities have been excluded and in whom the history and physical examination exemplify classic signs and symptoms of biliary disease we show in this study that cholecystokinin cholescintigraphy with calculation of gallbladder ejection fraction is a predictor of pathology as well as subsequent symptom relief after cholecystectomy. The spectrum of pathology that makes up chronic acalculous biliary disease lacks a distinct definition, yet this review shows that cholecystokinin cholescintigraphy offers the surgeon the means to better counsel his or her patient with regard to surgical indications, options, and benefits. We reviewed 26 patients who had no gallstones detectable, had gallbladder ejection fraction <35 per cent, and were status postlaparoscopic cholecystectomy for suspected chronic acalculous biliary disease. Our results show histopathologic evidence of chronic cholecystitis in 100 per cent, and 92 per cent of the patients had improvement of symptoms and satisfaction with the operation to the point that they would undergo the surgery again without reservation.

Endosonography/bile drainage combination for difficult-to-diagnose gallbladder disease.

The diagnosis of cholecystitis and cholelithiasis is often straightforward, particularly when transabdominal ultrasound (TUS) reveals gallstones or other abnormalities of the gallbladder. There remain many patients, however, with typical biliary pain and normal findings on TUS. This latter group of patients, in which women constitute a large majority, often undergo considerable suffering. Their medical care can also be quite costly. Cholecystokinin cholescintigraphy and stimulated biliary drainage (SBD) have been proposed for difficult-to-diagnose gallbladder disease, but they both have limitations. Cholecystokinin cholescintigraphy may not predict postoperative outcomes with a high degree of reliability. The processing and interpretation of bile drainage specimens is not standardized, and the sensitivity of SBD is less than that of endoscopic ultrasound (EUS). Combined endoscopic ultrasound and stimulated biliary drainage (EUS/SBD) offers a high degree of sensitivity in the diagnosis of cholecystitis and microlithiasis. Positive EUS/SBD is also highly correlated with long-term symptom resolution or relief following cholecystectomy.

Ampulla of Vater/duodenal wall spasm diagnosed by antroduodenal manometry.

Patients with chronic epigastric to right upper quadrant pain are often considered to have gallbladder of sphincter of Oddi dysfunction, but standard tests are nondiagnostic. In 62 consecutive patients with this compliant undergoing antroduodenal manometry, we correlated a change on duodenal motility with spasm of the ampulla of Vater/duodenal wall. This distinctive motility pattern occurred and was analyzed in 35% of patients. It is characterized by increased duodenal wall tone with phasic contractions of 19-22 or 41-44 contractions/min or by phasic activity alone. The subjects with spasm also underwent cholecystokinin cholescintigraphy, and 50% showed either significantly delayed gallbladder emptying of hilum to small intestine emptying, or both. The disorder appears to be secondary to a loss of neural inhibitory control and a dysfunctional small-bowel pacemaker. Antroduodenal manometry is an essential diagnostic procedure that complements sphincter of Oddi manometry in evaluation of unexplained right upper quadrant pain.

Correlation of abnormal cholecystokinin cholescintigraphy with patient outcome: [formula omitted], A.A. Starpoli, J.G. Robilotti, and N.N. Gualtieri. St. Vincent's Hospital and Medical Center of New York, Dept. of Medicine, Section of Gastroenterology, New York, New York

Correlation of abnormal cholecystokinin cholescintigraphy with patient outcome: [formula omitted], A.A. Starpoli, J.G. Robilotti, and N.N. Gualtieri. St. Vincent's Hospital and Medical Center of New York, Dept. of Medicine, Section of Gastroenterology, New York, New York

Abnormal gallbladder nuclear ejection fraction predicts success of cholecystectomy in patients with biliary dyskinesia

The management of patients with symptoms consistent with biliary tract disease who do not have gallstones is difficult. We retrospectively reviewed the charts of 18 patients who underwent cholecystokinin cholescintigraphy at our institution to determine if this procedure was reliable in identifying patients who would benefit from cholecystectomy. All patients underwent biliary screening, and a gallbladder ejection fraction of less than or equal to 35% was considered abnormal. None of the patients had evidence of gallstones by ultrasound. There were 11 patients with abnormal ejection fractions. All 11 patients (100%) had "classic" biliary colic and underwent cholecystectomy. The pathologic diagnosis was chronic cholecystitis in every patient. All patients had complete relief of their symptoms postoperatively with a mean follow-up of 10 months. There were six patients with normal ejection fractions. Only one patient in this group had "classic" biliary colic. This patient had a gallbladder ejection fraction of 38% and endoscopic evidence of gastritis. This patient remains symptomatic despite H2 blockade. The remaining five patients had nonspecific right upper quadrant or epigastric pain. These patients had endoscopic evidence of gastritis, and symptoms were relieved with H2 blockade. The remaining patient had an indeterminate scan due to radioactivity in the duodenum overlying the gallbladder and was excluded from this analysis. Cholecystokinin cholescintigraphy is a useful test in identifying those patients with biliary dyskinesia or acalculous cholecystitis who will benefit from cholecystectomy.

Chronic biliary-type pain in the absence of gallstones: the value of cholecystokinin cholescintigraphy.

Radiologic criteria for the diagnosis of gallbladder disease largely rest on the detection of calculi. Surgeons are reluctant to do a cholecystectomy in patients with symptoms of gallbladder disease if the results of sonography or cholecystography are normal. Consequently these patients are often left with no satisfactory treatment. Such patients may have chronic acalculous cholecystitis, partial obstruction of the cystic duct, or gallbladder dyskinesia. Increasing evidence indicates that at least some of these patients have decreased gallbladder emptying in response to a stimulus such as a test meal or cholecystokinin. Impaired emptying shown by cholecystokinin cholescintigraphy may be useful for predicting which patients with typical biliary-type pain but no evidence of calculi will be cured by cholecystectomy.

Cholescintigraphy in acalculous biliary pain: if abnormal, should cholecystectomy follow?

A 45-minute infusion of an octapeptide of cholecystokinin (Kinevac; Squibb Diagnostics, New Brunswick, NJ) was used to measure the gallbladder ejection fraction during cholescintigraphy in 40 normal volunteers. Cholecystokinin cholescintigraphy was shown to be a reproducible test. The maximum mean gallbladder ejection fraction occurred 15 minutes after cholecystokinin infusion and was 74.5% ± 1.9% (mean ± SEM). A gallbladder ejection fraction >40% (mean – 3SD) was arbitrarily defined to be normal. The gallbladder ejection fraction test was then used to identify patients with acalculous biliary symptoms who may respond to cholecystectomy. A total of 103 patients was tested; 21 had abnormal gallbladder ejection fractions and were randomized into two groups, cholecystectomy or no operation. These patients were followed up symptomatically at 3-month intervals for 13–54 months (mean, 34 months). Of the 11 patients who underwent cholecystectomy, 10 (91%) lost their symptoms and 1 improved. Of the 10 patients in the group that did not undergo surgery, all continued to be symptomatic, 2 of whom requested cholecystectomy after 13 and 24 months, respectively. Of the 13 gallbladders obtained from surgery, 12 showed evidence of chronic cholecystitis, muscle hypertrophy, and/or narrowed cystic duct. A normal gallbladder ejection fraction was recorded in 82 patients, and further treatment was left to the discretion of their referring clinician. On follow-up, 50 patients were asymptomatic and 10 were symptomatic without specific treatment of the biliary tract; 14 underwent cholecystectomy, 8 of whom were asymptomatic. Pathological abnormalities were recorded in 6 of the removed gallbladders. It is concluded that the gallbladder ejection fraction obtained after a 45-minute infusion of cholecystokinin during cholescintigraphy is a reproducible measure of gallbladder emptying, and that cholecystectomy alleviates the biliary-type pain of patients with a reduced gallbladder ejection fraction.

Acalculous biliary pain: Cholecystectomy alleviates symptoms in patients with abnormal cholescintigraphy

A 45-minute infusion of an octapeptide of cholecystokinin (Kinevac; Squibb Diagnostics, New Brunswick, NJ) was used to measure the gallbladder ejection fraction during cholescintigraphy in 40 normal volunteers. Cholecystokinin cholescintigraphy was shown to be a reproducible test. The maximum mean gallbladder ejection fraction occurred 15 minutes after cholecystokinin infusion and was 74.5% ± 1.9% (mean ± SEM). A gallbladder ejection fraction > 40% (mean − 3SD) was arbitrarily defined to be normal. The gallbladder ejection fraction test was then used to identify patients with acalculous biliary symptoms who may respond to cholecystectomy. A total of 103 patients was tested; 21 had abnormal gallbladder ejection fractions and were randomized into two groups, cholecystectomy or no operation. These patients were followed up symptomatically at 3-month intervals for 13–54 months (mean, 34 months). Of the 11 patients who underwent cholecystectomy, 10 (91%) lost their symptoms and 1 improved. Of the 10 patients in the group that did not undergo surgery, all continued to be symptomatic, 2 of whom requested cholecystectomy after 13 and 24 months, respectively. Of the 13 gallbladders obtained from surgery, 12 showed evidence of chronic cholecystitis, muscle hypertrophy, and/or narrowed cystic duct. A normal gallbladder ejection fraction was recorded in 82 patients, and further treatment was left to the discretion of their referring clinician. On follow-up, 50 patients were asymptomatic and 10 were symptomatic without specific treatment of the biliary tract; 14 underwent cholecystectomy, 8 of whom were asymptomatic. Pathological abnormalities were recorded in 6 of the removed gallbladders. It is concluded that the gallbladder ejection fraction obtained after a 45-minute infusion of cholecystokinin during cholescintigraphy is a reproducible measure of gallbladder emptying, and that cholecystectomy alleviates the biliary-type pain of patients with a reduced gallbladder ejection fraction.

Use of CCK Cholescintigraphy to Differentiate Choledochal Cyst from Gallbladder

A 17-year-old girl presented with right upper quadrant pain and was found to have a subhepatic cyst by ultrasound and CT. A DISIDA scan showed prompt filling of both the gallbladder and a very dilated common bile duct consistent with a choledochal cyst. Following intravenous administration of cholecystokinin, there was immediate emptying of the gallbladder into the cyst. Quantitative cholecystokinin cholescintigraphy may be a useful adjunct in the differentiation of choledochal cyst from gallbladder activity.