Normal Gallbladder Ejection Fraction Research Articles

HPB P07 HIDA scan utilisation and its influence on the management of patients with Gallbladder Dysmotility Disorders – A Retrospective Multicentre Cohort Study

Abstract Background Hepatobiliary Iminodiacetic Acid (HIDA) - Cholecystokinin (CCK) and fatty meal scan is widely used in the investigation of patients with acalculour biliary-like pain as they present a significant diagnostic and management challenge to the healthcare system. This scan detects functional capacity of gallbladder in the form of gallbladder ejection fraction (GBEF). GBEF of <35% is consistent with biliary dyskinesia and >80% with hyperkinesia, a recently postulated pathology. Laparoscopic cholecystectomy (LC) remains the treatment of choice of for both the entities. We performed audit of utility of HIDA scan and interpretation of its results across three sites. Methods A retrospective cohort study of patents undergoing HIDA scan across three hospitals between January 2015 and December 2022. Patients with biliary pain according to ROME IV criteria of functional GI disorders were included. Electronic case notes were reviewed and demographics, laboratory results of bilirubin and ALP, radiological investigations, endoscopy result and HIDA scan result. Results A total of 225 patients underwent HIDA scan; median age was 42 years (IQR 34-53) and 194 (86.2%) were female. Median time form the onset of symptoms to HIDA scan was 19 months (IQR 6-24). 35 (15.5%) had GBEF <35%, 157 (69.7%) with GBEF 36-79%, and 33 (14.6 %) had GBEF ≥80. 36 patients had LC after HIDA scan: 19 (52.7%) for biliary dyskinesia, 12 (33.3%) for microlithiasis and/or biliary sludge on EUS and 5 (13.8%) had it for symptoms but normal GBEF. Histopathology of 4 patients had normal gallbladder, while 27 had chronic cholecystitis and/or cholesterosis. Conclusions HIDA scan is vital investigation for recurrent biliary-like pain without presence of gallstones and gallbladder dysmotility is not uncommon in this group of patients. HIDA scan should be more liberally utilised to rule out gallbladder dysmotility. Reporting method of HIDA scan should also be standardised to help interpret the results accurately.

Defining Biliary Hyperkinesia and the Role of Cholecystectomy.

Functional gallbladder disorder is most commonly defined by biliary colic and low ejection fraction (EF) on cholescintigraphy. Biliary hyperkinesia is a controversial type of functional gallbladder disorder, and its definition and the role of cholecystectomy in treating functional gallbladder disorder remains unclear. We conducted a retrospective review of patients who underwent cholecystokinin-stimulated cholescintigraphy and cholecystectomy at 3 Mayo Clinic sites between 2007 and 2020. Eligible patients were 18 years or older, presented with symptoms of biliary disease, had an EF greater than 50%, underwent cholecystectomy, and had no evidence of acute cholecystitis or cholelithiasis on imaging. We used receiver operating characteristics curve analysis to identify the optimal cutoff value that predicted symptom resolution within 30 days of cholecystectomy. A total of 2,929 cholecystokinin-stimulated cholescintigraphy scans were performed during the study period; the average EF was 67.5% and the median EF was 77%. Analyzing those with EFs greater than or equal to 50% yielded 1,596 patients with 141 (8.8%) going on to have cholecystectomy. No significant differences were found in age, sex, BMI, final pathology between patients with and without pain resolution. Using a cutoff EF of 81% was significantly associated with pain resolution after cholecystectomy (78.2% for EF greater than or equal to 81% vs 60.0% for EF less than 81%, p = 0.03). Chronic cholecystitis was found in 61.7% of the patients on final pathology. We determined that an EF cutoff of 81% is a reasonable upper limit of normal gallbladder EF. Patients with biliary symptoms and an EF greater than 81% but no evidence of biliary disease on ultrasound or scintigraphy can be classified as having biliary hyperkinesia. Based on our findings, we recommend cholecystectomy for this patient population.

Pediatric Normokinetic Biliary Dyskinesia: Pain with Cholecystokinin on Hepatobiliary Iminodiacetic Acid Scan Predictive of Symptom Resolution After Cholecystectomy.

Introduction: Biliary dyskinesia is typically defined as a gallbladder ejection fraction (EF) <35% on hepatobiliary iminodiacetic acid scan with cholecystokinin stimulation (CCK-HIDA) testing. Cholecystectomy often leads to resolution of associated biliary colic symptoms. Alternatively, there is a subset of symptomatic patients with normal gallbladder EF on CCK-HIDA. It has been proposed that pain with CCK injection is more predictive of symptom resolution after cholecystectomy than low gallbladder EF. We reviewed our experience with pediatric patients with positive CCK provocation testing and a normal gallbladder EF in the absence of gallstones. Materials and Methods: We retrospectively reviewed the records of all pediatric patients with normal hepatobiliary iminodiacetic acid EFs (35%-80%) and pain with CCK injection at a tertiary care center between 2016 and 2020. Age, gender, body mass index (BMI), CCK-HIDA results, and pathology analysis were noted. Short- and long-term resolution of symptoms was determined by patient self-reporting at a mean of 3 weeks and 46 months, respectively. Results: Seventeen patients met inclusion criteria. Average age was 15.1 years (range, 12-17 years) with median BMI 24.9 (± 4.9 kg/m2). Mean CCK-HIDA EF was 56.3% (± 11.4%). In total, 62.5% of patients had evidence of chronic cholecystitis and/or cholesterolosis on pathology analysis. Of patients available for short-term and long-term postoperative follow-up, 80% and 83% reported complete or near complete resolution of symptoms, respectively. Conclusions: Normokinetic biliary dyskinesia is poorly understood but appears to be associated with chronic inflammation and cured by surgical intervention. Laparoscopic cholecystectomy results in resolution of symptoms for a majority of patients and should be considered in those with pain with CCK injection despite normal imaging studies. Clinical Trial Registration Number: 1657640-2.

Sincalide-Stimulated Cholescintigraphy: A Retrospective Study and Proposal of a Modified Workflow.

Current guidelines for sincalide-stimulated cholescintigraphy (SSC) call for a 60-minute sincalide infusion, and a gallbladder ejection fraction (GBEF) ≥38% is considered normal. In this retrospective study, we hypothesize that most patients reach a normal GBEF by 30 minutes. Eligible patients had undergone a 60-minute SSC from January to December 2019. The clinical SSC data were previously processed on a Xeleris workstation (GE Healthcare). In subjects with GBEF ≥38% based on standard SSC, the GBEF at 20 minutes and 30 minutes were retrospectively calculated using manual pixel height measurements. Receiving operating characteristic was analyzed to determine the best GBEF cutoff at 30 minutes. Of 302 subjects, mean age of 46 ± 17 years, 33 (10.9%) showed an abnormal GBEF <38% suggestive of functional gallbladder disorder. In the remaining 269 patients (89.1%) with a normal GBEF, 60.6% and 86.6% reached a normal GBEF at 20 minutes and 30 minutes, respectively. Moreover, a GBEF threshold >29.1% at 30 minutes was associated with a negative predictive value of 99.6%, indicating that a 60-minute SSC was not necessary. The GBEF values were not associated with sex, age, patient symptoms, or type of referral. Manually calculated GBEFs on the time-activity curve showed excellent correlation with the primary values. We propose a modified workflow that splits the 60-minute SSC into two 30-minute image sets to allow for a screening GBEF at 30 minutes. If GBEF is >29.1% at 30 minutes, the second image set may be stopped, and the examination is complete. The majority of patients (77.2%) undergoing the standard 60-minute SSC reach a normal GBEF already by 30 minutes. The proposed workflow shortens the SCC procedure by 30 minutes, while maintaining high diagnostic accuracy and contributing to improved procedure efficiency and reduced patient discomfort as well as symptoms.

Clinical utility of stimulated cholescintigraphy using a standardized Ensure-Plus fatty meal protocol in patients with suspected functional gallbladder disorder: a retrospective study of seven-years clinical experience.

The clinical utility of fatty meal stimulated cholescintigraphy particularly using a standardized formulation in patients with suspected functional gallbladder disorder has not been extensively studied. We present our seven-year clinical experience using an Ensure plus protocol. A retrospective study was performed on patients undergoing stimulated cholescintigraphy using Ensure Plus for evaluation of suspected functional gallbladder disorder. A gallbladder ejection fraction (GBEF) of <33% was considered abnormal. Of the 173 patients evaluated, 57 (33%) had an abnormal GBEF, 112 (65%) had a normal GBEF and 4 (2%) had no gallbladder visualization. Of the 57 patients with an abnormal GBEF, symptom improvement occurred in 30/31 (97%) who underwent cholecystectomy and in 17/26 (65%) who were managed conservatively (p= 0.003). Of the 112 patients with a normal GBEF, symptom improvement occurred in 8/10 (80%) who underwent cholecystectomy and 74/102 (73%) who were managed conservatively (p= 1.000). In the subgroup of 102 patients with a normal GBEF managed conservatively, those without symptomatic improvement had lower GBEFs compared to those with symptomatic improvement (median GBEF 46% versus 57%, p= 0.019). Our retrospective results support a clinical role for stimulated cholescintigraphy using Ensure Plus in the evaluation of patients with suspected functional gallbladder disorder. While an abnormal GBEF predicts good surgical outcome, our results suggest that using an absolute GBEF cut off value of <33% may not apply to all patients and hence GBEF results should only be used as an adjunct in the surgical decision-making process.

Gallbladder motility in children with celiac disease before and after gluten-free diet.

BackgroundGallbladder (GB) hypomotility has been reported in adults with celiac disease (CD), but there is no literature on GB dysfunction in children with CD. We aimed to study GB motility in children with CD, before and after a gluten-free diet (GFD), using ultrasonography (USG) and technetium-99 labeled mebrofenin hepatobiliary scintigraphy (HBS).MethodsChildren with newly diagnosed CD were enrolled and evaluated for GB ejection fraction (GBEF) using HBS and USG. Those with reduced GBEF on initial HBS were again evaluated after 6 months of strict GFD and the results were compared.ResultsOf the 50 children with CD (mean age 9±2.1 years, 54% boys), 16% (n=8) had a low GBEF at baseline (19±13%). These children had a significantly greater delay in diagnosis compared to those with normal GBEF (6.5±2.0 vs. 2.3±1.2 years, P<0.001). A significant improvement in GBEF was noted on HBS post GFD (74±12%1 vs. 9±13%, P<0.001). GBEF also improved significantly as assessed by USG parameters after GFD (P<0.001). The fasting GB volume decreased (5.7±1.4 vs. 10.2±2.6, P=0.002), with a significant improvement in percentage postprandial GB volume change (52±10.5% vs. 24±16.5%, P=0.007) compared to baseline pre-GFD values. Orocecal transit time was also increased in children with reduced GBEF.ConclusionsGB function is impaired in at least 16% of children with CD at diagnosis and is reversible with GFD. GB dysfunction is significantly associated with a delayed diagnosis and may be a part of general gastrointestinal dysmotility.

Relations between Hepatobiliary Scintigraphy Findings and Histopathological Factors in Patients with Recurrent Biliary Colic

Background: The histopathological factors of gallbladder that affect the findings of hepatobiliary scintigraphy is not fully known. The aim of the present study is to investigate the relationship between hepatobiliary scintigraphy findings and histopathological results in patients with recurrent biliary colic. Methods: A total of 107 patients who underwent hepatobiliary scintigraphy for recurrent biliary colic and subsequent cholecystectomy were retrospectively enrolled. According to the hepatobiliary scintigraphy findings, patients were categorized into three groups; patients with non-visualization of gallbladder activity (non-visualized GB group), gallbladder ejection fraction (GBEF) of < 35% (low GBEF group), and GBEF of ≥ 35% (normal GBEF group). Results: Of all patients, 31 patients were classified as non-visualized GB group, 33 were low GBEF group, and 43 were normal GBEF group. Non-visualized group showed higher rates of patients with severe neutrophil, lymphoplasma cell, and eosinophil infiltrations and empyema and showed more increased cystic duct wall thickness than other groups (p< 0.05). Low GBEF group showed higher muscle-to-total wall thickness ratio and muscle-to-fibrosis thickness ratio than those with normal GBEF group (p< 0.05). On multivariate logistic regression analysis, Severe degrees of lymphoplasma cell infiltration (p=0.027) and eosinophil infiltration (p< 0.001) were independent predictors for non-visualization gallbladder activity, and muscle-to-fibrosis thickness ratio (p=0.030) was an independent predictor for low GBEF. Conclusions: In patients with recurrent biliary colic, non-visualization of gallbladder activity on hepatobiliary scintigraphy was related with the degree of inflammation in the gallbladder, while GBEF was related with muscular hypertrophy of the gallbladder.

Cholescintigraphy may have a role in selecting patients with biliary dyskinesia for cholecystectomy: a systematic review.

Patients with typical biliary pain, no gallstones on ultrasound and low gallbladder ejection fraction (GBEF) on cholescintigraphy (gallbladder dyskinesia) may be considered for a laparoscopic cholecystectomy. However, some studies have suggested that symptoms alone are an adequate indication for laparoscopic cholecystectomy. The aim was to determine the role of cholescintigraphy in predicting outcomes of cholecystectomy in patients with typical and atypical biliary symptoms and normal biliary ultrasound. Meta-analysis using Preferred Items for Systematic reviews and Meta-Analysis (PRISMA) guidelines of published literature using several electronic databases. Twenty-four articles were selected with a total of 1710 patients. The majority (n = 1633, 94.4%) of patients had typical biliary symptoms. A total of 1047 patients with typical symptoms and a reduced GBEF had a cholecystectomy with 852 (81.4%) having complete resolution of symptoms. A total of 148 with typical symptoms and normal GBEF had a cholecystectomy with 103 (69.5%) having complete resolution, which was significantly less than those with a reduced GBEF (odds ratio 1.65, confidence interval 1.08-2.05, P = 0.01). Forty-five patients with atypical symptoms and a reduced GBEF had a cholecystectomy with 31 (68.9%) having complete resolution of symptoms, which is significantly lower than those with typical symptoms (odds ratio 1.97, confidence interval 0.95-3.90, P = 0.05). Cholescintigraphy improved the predication of outcome of cholecystectomy in biliary dyskinesia by 10%. However, the presence of typical symptoms does predict an effective response in 70% of patients. Atypical symptoms predict a poorer response.

Relations between hepatobiliary scintigraphy findings and histopathological factors in patients with recurrent biliary colic.

The aim of the present study was to investigate the relationship between hepatobiliary scintigraphy findings and histopathological results in patients with recurrent biliary colic. We retrospectively enrolled 107 patients who underwent hepatobiliary scintigraphy for recurrent biliary colic and subsequent cholecystectomy. According to the hepatobiliary scintigraphy findings, patients were categorized into a nonvisualization of gallbladder activity (nonvisualized GB) group, low gallbladder ejection fraction (GBEF) group, and normal GBEF group. Differences in histopathologic factors between the three groups were evaluated and multivariate logistic regression analyses were performed to identify histopathological predictors for hepatobiliary scintigraphy findings. The nonvisualized group had a higher frequency of patients with empyema and severe infiltration by neutrophils, lymphoplasma cells, and eosinophils. The low GBEF group had a higher muscle-to-total wall thickness ratio and muscle-to-fibrosis thickness ratio of the gallbladder wall than those in the normal GBEF group. On multivariate logistic regression analyses, severe degrees of lymphoplasma cell infiltration and eosinophil infiltration were independent predictors for nonvisualization of gallbladder activity, and a higher muscle-to-fibrosis thickness ratio was an independent predictor for low GBEF. In patients with recurrent biliary colic, nonvisualization of gallbladder activity on hepatobiliary scintigraphy was related to the degree of inflammation in the gallbladder, while low GBEF was related to muscular hypertrophy of the gallbladder.

Systematic review with meta-analysis: cholecystectomy for biliary dyskinesia-what can the gallbladder ejection fraction tell us?

Gallbladder dyskinesia (gallbladder spasm, biliary dyskinesia or chronic acalculous cholecystitis) is a poorly defined entity which presents as biliary-type pain without any identifiable organic pathology. Abnormal gallbladder ejection fraction (GBEF) is used by some to select those likely to benefit from cholecystectomy. The validity of this approach has been questioned. To systematically review the literature and summarise the evidence surrounding the practice of cholecystectomy based on GBEF for gallbladder dyskinesia. We conducted a systematic search of PubMed/MEDLINE and SCOPUS from 1980 to 2016 to identify the relevant literature. Twenty-nine studies including 2891 patients were included in the final analysis. In comparing cholecystectomy with medical management, patients with a normal GBEF did not benefit from cholecystectomy; whereas those with low GBEF had a higher chance (RR, relative risk=2.37) of symptomatic improvement following surgery. When those classified as "low" and "normal" GBEF were compared in terms of outcome following cholecystectomy, the rate of improvement following surgery was similar in the two groups (RR 1.09) which suggests a placebo effect of surgery. While a low GBEF may provide some guidance in identifying those with gallbladder dyskinesia who may benefit from cholecystectomy, the available data are inconsistent and based on studies of poor quality which are often subject to bias and the impact of confounding factors. For these reasons, we conclude that the role of scintigraphy and cholecystectomy in the definition and management of this disorder remain unclear pending definitive study.

Scintigraphic Findings Beyond Ejection Fraction on Hepatobiliary Scintigraphy: Are They Correlated With Chronic Gallbladder Disease?

To determine if classically reported findings associated with chronic cholecystitis on hepatobiliary scintigraphy (HBS), such as delayed small bowel (SB) transit, slow gallbladder (GB) filling, and reversal of the normal GB and SB transit, are associated with a depressed GB ejection fraction (GBEF). The secondary objectives were to determine whether GBEF is correlated with the time of GB filling, time of SB transit, or reversal of normal GB/SB filling sequence. We hypothesize that an association between a depressed GBEF and these classical HBS findings could validate them as surrogate markers for chronic GB disease. We reviewed all HBS exams over a retrospective 16-month period. Data from 221 patients (mean age, 45.3 ± 15.2 years; 152 female and 69 male subjects) who underwent HBS with GBEF determination for evaluation of chronic symptoms concerning for biliary etiology met inclusion criteria. Classically reported findings for cholecystitis were recorded for each patient. Comparisons were made using t test and Fisher test analysis. Comparing exams with normal and abnormal GBEF values, there were no significant differences based on age, sex, GB fill time, normal versus delayed SB transit, and reversal of normal GB/SB filling sequence. Additionally, we did not see a correlation between the measured GBEF and GB fill time, SB transit time, or reversal of normal GB/SB filling sequence. Delayed SB transit, slow GB filling time, and reversal of the normal GB and SB filling sequence on HBS imaging are not associated with the measured GBEF and not predictive of chronic GB disease.

Poor Reproducibility of Gallbladder Ejection Fraction by Biliary Scintigraphy for Diagnosis of Biliary Dyskinesia

Twenty percent of cholecystectomies in the US are performed for a diagnosis of biliary dyskinesia. Diagnosis is made by measuring gallbladder ejection fraction (GbEF) using hepatobiliary scintigraphy. Our purpose was to evaluate the reproducibility of GbEF measurements. This is a retrospective review of patients referred for cholecystectomy, from 2010 to 2016, with a diagnosis of biliary dyskinesia based on a GbEF test, who then underwent a repeat GbEF test. Thirty consecutive patients were identified by hospital records. Re-testing of GbEF was performed at least 6 weeks after the initial test using Tc-99m and slow injection of sincalide at 0.02 mcg/kg. On re-testing, 16 of 30 patients (53%) patients had a normal GbEF of >35%, ie the initial test result was not reproducible in them. Age, sex, days between testing, and initial GbEF did not differ between groups. The 14 patients who re-tested positive for biliary dyskinesia with reduced GbEF were significantly more likely to have episodic pain than steady pain. Re-testing frequently resulted in change in management in that most patients who re-tested in the normal range were not offered cholecystectomy. Hepatobiliary scintigraphy with GbEF is a poorly reproducible test. Re-testing resulted in a change in management in many patients who then avoided cholecystectomy. Strong consideration should be given to repeating hepatobiliary scintigraphy with GbEF before cholecystectomy in patients with an initial positive test.

Utility of HIDA Scan in Predicting Outcome of Cholecystectomy in Patients With Chronic Acalculous Gallbladder Disease? A Systematic Review

Introduction: HIDA scan with gallbladder ejection fraction (GBEF) is used to evaluate chronic acalculous gallbladder disease (CAGBD), in which abdominal pain is attributable to biliary dyskinesia or chronic acalculous cholecystitis. In current practice, cholecystectomy is recommended when the GBEF is abnormal. We conducted a systematic review to evaluate the value of HIDA to predict patient response after cholecystectomy. Methods: In consultation with librarian, a literature search was done in PubMed for studies from January 1st 1990 - October 31st, 2016 to identify manuscripts with patients with abdominal pain without gallstones who underwent HIDA followed by cholecystectomy, and where follow-up data on pain resolution following surgery was reported. After pooling data, summary statistics were calculated for positive predictive value (PPV), negative predictive value (NPV), sensitivity and specificity of HIDA with abnormal GBEF in detecting patients whose symptoms resolve after cholecystectomy. Results: Initial literature search identified 74 articles. 15 studies met the inclusion criteria. Only 1 randomized controlled trial was identified (Yap et al.), which was small and low quality. 722 patients underwent cholecystectomy in the abnormal GBEF group, out of which 658 reported improvement (PPV = 91.1%). In the normal GBEF group, 132 patients underwent cholecystectomy and 107 patients reported improvement (NPV = 18.9%). Overall the sensitivity of HIDA EF was fairly high at 86.0% but the specificity was low (28.1%), corresponding to a false positive rate of 71.9%. The overall positive likelihood ratio (LR) is 1.20 and negative LR is 0.50. Conclusion: While the sensitivity and PPV of HIDA for detecting patients who have cholecystectomy responsive CAGBD is fairly high, the specificity is alarmingly low. This means that the majority of patients who don't improve following cholecystectomy have abnormal HIDA scans preoperatively. Also, a relatively high proportion of patients with normal HIDA scans report improvement in symptoms following surgery, which undermines the value of test. These findings indicate that HIDA scans may be less valuable in selecting patients for cholecystectomy, as a test with a high specificity would be better for this purpose. We suggest that physicians perform comprehensive evaluations to rule out other causes of abdominal pain before proceeding to HIDA, and to interpret findings of HIDA with caution, as well as educate patients regarding the limitations.Figure: Test characteristics of HIDA scan.Table. 2x2: table with summary data for all patients with preoperative HIDA scans undergoing cholecystectomy.Table: Studies included in review.

Oral Cholecystagogue Cholescintigraphy: A Systematic Review of Fatty Meal Options.

Intermittent unavailability of sincalide for determination of gallbladder ejection fraction (GBEF) prompted increased usage of fatty meal cholecystagogues (FMCs). The aim of this systematic review was to identify the state of current FMC options in cholescintigraphy, focusing on the quality of corresponding normal GBEF values. We performed an extensive literature search of the MEDLINE, Cochrane, and CINAHL databases without date or language restrictions with a broad spectrum of search terms. Selection criteria required both that the study use a FMC as part of a stimulated GBEF examination to gather data on normal volunteers or patients without evidence of gastrointestinal disease and that the meal used be described sufficiently for emulation. A cumulative point system was used to grade the quality of normal GBEF values: 1 point for screening ultrasound, 1 point for detailed screening questionnaire, 1 point for 20 or greater number of participants in a study, 1 additional point for 60 or greater number of participants in a study, 0.5 points for cursory screening questions, and 0 points when no screening process was mentioned. The meal was expressed in grams of fat per volume, when available. Twelve studies met inclusion criteria out of 15 studies claiming to report normal values. Two studies (17%) achieved a score of 3, 5 studies (42%) at 2 to 2.5, 3 studies (25%) at 1 to 1.5, and the remaining 2 studies (17%) at 0 to 0.5. Total number of participants examined ranged from 6 to 100. Meal composition varied widely. In 1 study, sham feeding was used. Most meals had components that could present problems to patients with relatively common dietary restrictions (ie, lactose intolerance, egg protein allergy, etc). Results for proposed normal values varied widely (from 16.3% to 85.6%). The commercial fatty meal products of Humana Infant Formula 1 and Ensure Plus offered the highest-quality normal values. There is a need to establish high-quality normal GBEF range for a ubiquitous fatty meal (ie, a meal that would be widely available, easy to prepare, inexpensive, and free of sensitivity-provoking ingredients). A corn oil emulsion, has immense potential as an ideal FMC, limited currently only by its lack of established normal values. Currently, the highest-quality normal GBEF values available for FMC exist for 2 commercial products, Humana Infant Formula 1 and Ensure Plus. However, these products may not be readily available at some institutions, and neither one is free from dietary restrictions.

Clinical Predictors of Gallbladder Dyskinesia

Introduction: Gallbladder dyskinesia (GD) is defined as biliary pain in the absence of gallstones. The diagnosis relies on cholecystokinin-stimulated cholescintigraphy (HIDA) to show decreased gallbladder ejection fraction (GBEF). There are no well-defined clinical parameters for predicting gallbladder dyskinesia in patients presenting with abdominal pain suspicious of gallbladder dysmotility. The aim of this study is to assess the clinical predictors of gallbladder dyskinesia in a cohort of patients with abdominal pain and no evidence of gallstone undergoing HIDA study. Methods: A prospective study of patients with the chief complaint of abdominal pain and negative abdominal ultrasound for gallstone disease who were referred by their physicians for HIDA scan from January 2013 to May 2014. Patient demographics, medical and surgical history, drug use (affecting GI motility), proton pump inhibitor use, and other diagnostic tests were collected. All patients answered validated PAGI-SYM and PAC-SYM questionnaires. Following an overnight fast, all patients underwent a standardized CCK-stimulated HIDA study. Calculated GBEF of less than 35% was considered abnormal. A univariate and multivariate logistic regressions model was used to identify independent predictors for gallbladder dyskinesia and p<0.05 was considered significant. Results: From 169 patients who had been referred for HIDA study between January 2013 to May 2014, 67 agreed to participate in the study. Participants recruited to the study had a mean age of 43 years, 67% females, 73% Caucasians, average BMI 29 kg/m2, 28% smokers, and 32% alcohol users. Overall symptom frequency was as following: upper abdominal pain 100%, nausea 70%, constipation 45%, bloating 34%, vomiting 5%. Among participants, 34 (51%) patients had gallbladder dyskinesia on HIDA study. Constipation and narcotic medication use were significant predictors for delayed GBEF on HIDA study on univariate analysis. Patients with gallbladder dyskinesia were more likely to take narcotic pain medications compared to patients with normal gallbladder ejection fraction. Constipation symptom score (PAC-SYM total score) of 3.1±0.6 was associated with low GBEF, compared to score of 1.2±0.7 in patients with normal GBEF (p<0.05). Severe constipation was the only predictor of gallbladder dyskinesia on multivariate analysis. Conclusion: In a cohort of patients presenting with biliary pain and negative sonographic findings of gallstones, severe constipation could predict gastroparesis. Larger pool of data is needed to confirm these findings.

Biliary dyskinesia and symptomatic gallstone disease in children: two sides of the same coin?

Despite lack of consensus criteria, biliary dyskinesia (BD) is an increasingly accepted pediatric diagnosis. We compared patient characteristics, outcomes, and resource utilization (before and after surgery) between children with BD and symptomatic cholecystolithiasis (LITH). Data from the electronic medical record were abstracted for children diagnosed with BD or LITH between December 1, 2002, and November 30, 2012, at Children's Hospital of Pittsburgh. Four hundred and ten patients were identified (BD: 213 patients, LITH: 197 patients). Patients with BD had significantly lower BMI, longer symptom duration, more dyspeptic symptoms, and were more likely to present with other symptoms. Forty-one patients (13.8%) with BD underwent cholecystectomy despite a normal gallbladder ejection fraction (GB-EF). In 32 of these, sincalide triggered pain compared to 75 of the 155 patients with low GB-EF. After surgery, patients with BD more commonly visited gastroenterology clinics and had more GI-related hospitalizations, while emergency room visits decreased in both groups. Only the nature of biliary disease independently predicted continuing pain after surgery, which in turn was the best predictor for higher resource utilization after cholecystectomy. A large percentage of children with BD did not meet the adult diagnostic standards. Compared to those with LITH, children with BD have more widespread symptoms and continue to use more clinical resources after surgery. These findings suggest that despite its benign prognosis, BD is increasingly treated like other potentially acute gallbladder diseases, although it has the typical phenotype of FGIDs and should be treated using approaches used in such disorders.

Diagnostic Stringency and Healthcare Needs in Patients with Biliary Dyskinesia

We have recently shown an increase in cholecystectomies for biliary dyskinesia. Based on these results, we hypothesized that diagnostic criteria are less stringently applied which may contribute to ongoing resource utilization. Using billing codes, patients seen for biliary dyskinesia were identified and data were extracted from the electronic medical record to confirm the diagnosis, obtain demographic and clinical data and assess resource utilization 1 year prior to and after cholecystectomy. A total of 972 patients were identified, with 894 undergoing cholecystectomy. In 259 patients, symptoms had started <3 months prior to evaluation. Functional gallbladder imaging revealed a mean gallbladder ejection fraction of 23.1 ± 0.7 %; of the patients undergoing surgery, 116 had a normal gallbladder ejection fraction. Sufficient up data for pre- and post-operative assessment of resource utilization was available for 368 patients. Emergency room (ER) visits decreased from 0.86 ± 0.07 to 0.69 ± 0.03 (P < 0.05), while hospitalization rates remained unchanged after surgery. Patients not meeting consensus criteria for the diagnosis of biliary dyskinesia were more likely to use opioids and have ER visits prior to and after cholecystectomy. Using multiple logistic regression benzodiazepine use, migraine history and prior ER visits independently predicted postoperative resource utilization. Our data demonstrate that a significant number of patients undergo cholecystectomy for biliary dyskinesia, even though they do not meet currently accepted diagnostic criteria. While healthcare resource utilization drops within the first year after surgery, ER visits and hospitalizations remain common, suggesting a more limited benefit of surgical approaches in these patients.

Sa1158 The Number of Drug Side Effects Is Associated With Greater Efficacy in IBS Clinical Trials: The Potential Influence of Unblinding

and after cholecystectomy were used as surrogate measure for resource utilization. RESULTS: Within the time frame of the study, 419 patients (79.4% women; age 42.4±0.7 years) were diagnosed with biliary dyskinesia, with all but 24 (94.3%) undergoing cholecystectomy. The mean duration of symptoms was 19.8±7.5 months; in 129 (30.8%) patients, symptoms had started less than 3 months prior to evaluation. Functional gallbladder imaging revealed a mean gallbladder ejection fraction of 22.4±1.0%, with 66 (15.8%) patients having normal results. Patients completed 3.2±0.1 diagnostic tests prior to being scheduled for cholecystectomy. Appropriate follow up data were available for 209 patients. Within the 12 months interval, ER visit and hospitalizations decreased from 1.0±0.1 to 0.7±0.2 (P=0.07) and from 0.3±0.04 to 0.26±0.06 (P=0.69), respectively. In univariate analyses, age, shorter disease duration, normal gallbladder ejection fraction, a history of chronic back pain and use of prescription opioids were associated with ongoing resource utilization after surgery. Using a multiple nonlinear regression model, younger age (OR 3.2; 95% CI: 1.2-8.2) and use of opioid analgesics (OR 3.7; 95% CI: 1.3-10.2) were independent predictors of ongoing resource utilization. CONCLUSIONS: Our data demonstrate a lowered threshold for cholecystectomy, as more than one third of the patients did not meet current consensus criteria for biliary dyskinesia. While we did not address the impact of surgery on symptoms, surgery has a marginal effect on resource utilization. The impact of coexisting disorders and opioid use on ongoing healthcare needs points at the role of non-gastrointestinal factors and argues against surgical approaches.

Chronic Dyspepsia with a Negative Workup: Consider an Early Cholecystokinin-HIDA Scan

Purpose: Dyspeptic symptoms are common in the general population, leading to frequent visits to the doctor and repeated diagnostic tests. Quite often no evidence of structural disease is found that would explain the symptoms. Cholecystokinin-HIDA scan (CCK-HIDA) provides a quantitative method for assessing gallbladder contraction and calculation of the gallbladder ejection fraction (GBEF). We hypothesize that CCK-HIDA would identify a functional gallbladder disorder as the cause of dyspeptic symptoms in a significant percentage of patients with previously negative workup. Methods: We performed a retrospective analysis of patients who underwent CCK-HIDA at our hospital between October 2009 and October 2011. We included patients whose abdominal ultrasound/CT scan, upper and lower GI endoscopy did not provide an explanation for their symptoms. We excluded patients with cholelithiasis/choledocholithiasis, previous sphincterotomy, any biliary surgery, and patients taking prokinetic medications. We collected demographic data, information regarding clinical presentation, abdominal ultrasound and/or CT scan, esogastroduodenoscopy, colonoscopy and CCK-HIDA; we documented GBEF, the presence of reflux into the gallbladder, and duodenogastric reflux. CCK-HIDA was performed according to a standardized protocol, with GBEF of 35% and below being considered abnormal. Data were analyzed using SPSS; parametric methods were employed. Results are shown as median (range). Results: Eighty-six consecutive patients underwent CCK-HIDA in our hospital during the above period; 63 patients (20 M/43 F) met the inclusion criteria; 42 of these patients (13 M/29 F) had evidence of negative GI workup as described above and were included in the analysis. Patients' median age was 52 (range 21-89). Forty-seven percent of patients complained of right upper quadrant pain at presentation; 23% had epigastric pain. Twenty-three out of the 42 patients (55%) had a low GBEF as defined above; median GBEF in this group was 19 (range 3-35). Five patients showed reflux into the gallbladder, or duodenogastric reflux. There was no significant difference between the patients with low and those with normal GBEF in terms of age (p=0.875) or gender (p=0.555). No correlation was found between age and GBEF overall. Conclusion: A significant percentage of patients with dyspeptic symptoms and otherwise negative GI workup exhibit a low GBEF. This is not associated with a particular age or gender. Employment of the CCK-HIDA early in the diagnostic process might help in elucidating faster the etiology of these complaints.

Cholecystokinin-Cholescintigraphy in Adults

Cholecystokinin-cholescintigraphy (CCK-CS) provides a physiologic, noninvasive, and quantitative method for assessing gallbladder contraction and calculation of a gallbladder ejection fraction (GBEF). At present, it is used most commonly to identify patients with suspected functional gallbladder disorder. However, the methodology of CCK infusion and normal values differ markedly among imaging centers. This document represents the consensus opinion of an interdisciplinary panel that gathered to assess the current optimal method for performing CCK-CS in adults, potential uses and limitations of CCK-CS, and questions that require further investigation. The panel recommended the use of a single, standardized, recently described CCK-CS protocol that involves infusion of 0.02 μg/kg of sincalide over 60 minutes with a normal GBEF defined as ≥38%. The panel emphasized the need for a large, multicenter, prospective clinical trial to establish the utility of CCK-CS in the diagnosis of functional gallbladder disease. Although not without controversy regarding its clinical utility, the primary indication for CCK-CS at present is the well-selected patient with suspected functional gallbladder disorder. Agreement was reached that the adoption of this standardized protocol is critical to improve how CCK-CS is used to direct patient care and will represent an improvement over the diverse methods currently in use by eliminating the current lack of uniformity and adding both reliability and credibility to the results.