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DISCLOSURE Gall-Bladder Scintigraphy - Useful Test or Waste of • Nothing to disclose Money?

Samuel Nurko MD MPH Center for Motility and Functional Gastrointestinal Disorders Boston Children’s Hospital

GALLBLADDER

• The function of the is to store, concentrate and transport from the liver into the . • Emptying of the GB is part of the process of food digestion • Abnormal GB function may therefore lead to pathology

GALLBLADDER GALLBLADDER SCINTIGRAPHY

• Structure • Anatomy • Acute – X-ray methods ( US, CT, MR) – Calculous – Acaluclous – Invasive (ERCP) • Chronic cholecystitis – Calculous – Acalculous Biliary • Function • Billiary obstruction – Billiary atresia – Scintigraphy – other • Standardized and quantitative method to • Billiary drainage evaluate gallbladder contraction/ emptying – Bile leaks

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ROME III BILIARY DYSKINESIA Adults • Defined as a disorder of the gallbladder and biliary tract that presents with pain, without sonographically apparent , and with an abnormal cholecystokinin (CCK)-stimulated gallbladder ejection fraction with a lack of any other clear cause for symptoms

Current Reports 2006, 8:172–176 Gastroenterology 2006; 130: 1498

BILIARY DYSKINESIA BILIARY DYSKINESIA Surgery? • The treatment of symptomatic patients with evidence of gallstones is well established How to treat symptomatic patients without – Laparoscopic gallstones and with an abnormal HIDA – 80 to 90% good results scan result is a decision conundrum for physicians, because there is still uncertainty as to whether surgery is truly beneficial. • 5% to 30% of performed annually are for diagnosed biliary dyskinesia

META-ANALYSIS

Five studies met the inclusion criteria, representing 274 patients. META-ANALYSIS

Patients undergoing surgical therapy for biliary dyskinesia were 2.79 times more likely to have symptomatic relief (98%) versus nonoperative therapy (32%) (95% confidence interval, 2.05–3.79).

Arch Surg. 2009;144(2):180-187 J Laparoendoscop Adv Surg Tec 2005

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META ANALYSIS

• Conclusions: Patients without gallstones who have right upper quadrant pain and a positive WHAT ABOUT HIDA scan result are more likely to experience symptom relief following cholecystectomy than CHILDREN? those treated medically. • There is, however, wide variability in data reporting, particularly with respect to symptom relief and duration of follow-up. • Cholecystectomy is indicated in symptomatic patients without gallstones who have a low– ejection fraction HIDA scan.

Arch Surg. 2009;144(2):180-187

CHOLECYSTECTOMY FOR BILIARY DYSKINESIA BILIARY DYSKINESIA Long term follow children 41 with mean follow-up of 8.4 months. • Twenty-eight patients (68.3%) had symptom • 38 children follow up 4.3 y (range, 0.15 to 13) resolution.Being overweight can be • Age was 12.3 years (range, 6 to 19) • 5 patientsconsidered in the cohort had a arelative normal ejection • 27/38 (71% complete resolution) fraction of at least 35%, and all 5 noted relief of their symptomscontraindication after surgical intervention. to • Predictors: • GBEFcholecystectomy < 15%, pain upon CCK injection,for biliary and a family – Presence of history of biliarydyskinesia. disease were not predictors of – A cholecystokinin-stimulated, gallbladder ejection symptomatic resolution fraction less than 15% (odds ratio, 8.00). • Non-overweight patients (body mass index–for-age – 11/13 children with an ejection fraction greater b85th percentile) were more likely to have symptom resolution than their overweight counterparts (odds than 15% did not have resolution of symptoms. ratio, 2.13).

J Pediatr Surg 2004; 39:813-816. Journal of Pediatric Surgery (2011) 46, 879–882

BILIARY DYSKINESIA SURGERY VS MEDICAL Surgery • Twenty-three children (median age, 14 years; 16 girls),

• Complete relief or marked improvement of symptoms after short-term follow-up was seen in 87% children

• LONG TERM: Sixteen responded. Overall, 67% of parents indicated that their children's symptoms were completely relieved after cholecystectomy, whereas 7% indicated that the symptoms were not relieved.

• In addition, the symptom questionnaires were sent to the parents of 41 children who were diagnosed with biliary Patients with BD whose symptoms were relieved by dyskinesia but did not undergo cholecystectomy. Only 9 (22%) parents responded. Of the respondents, none of them had any laparoscopic cholecystectomy had a lower mean BMI (24.84) , nausea, or vomiting, and 1 child had than patients in which symptoms persisted (27.17), and in the month before the administration of the questionnaire. persistent symptoms were more likely to be in females and those that had longer symptom duration. Am Surg 2008; 74: 587 Journal of Pediatric Surgery (2008) 43, 1060–1064

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SURGERY VS MEDICAL WHY??

• The children were divided into 2 groups: – Cholecystectomy (n = 35) • What defines an abnormal GBEF? – Controls no surgery (n = 20) – Sensitivity or specificity

• Follow up 3.7 years • Do we have the right technique? • 54.3% of the operative group had a complete – IV CCK vs oral Lipomul response to pain, and 20.0% had a partial response. Of those who did not have surgical intervention, • What are we diagnosing? 55.0% had complete pain resolution, and 20.0% had partial resolution of their pain. – Gallbladder dyskinesia vs other functional • Most patients with BD got better with time, regardless of treatment option, with a symptom relief – other peptic or organic diseases rate greater than 75% in the nonoperative group – dysfunction (much faster in surgical group)

Journal of Pediatric Surgery (2006) 41, 1894

DO WE HAVE THE WRONG SCINTIGRAPHY VARIABLES CUTT OFF?

• Length of the fast Outcome in patients with GBEF > 40% • Dose/ speed • Type of stimulation – Oral vs CCK – CCK bolus vs continuous

• Could the lack of specificity be related to the wide range of abnormal ejection fraction?

Gastroenterology 1991; 101: 786

Cutt-off value? <40% CUT-OFF? Meta-analysis • Symptomatic patients without evidence of gallstones and with a negative HIDA scan 362 patients that underwent result do benefit from surgery (57%-100% cholecystectomy symptomatic relief) • However, nonoperative intervention in this

group of patients leads to a better relief After cholecystectomy, 94% of the patients with reduced GBEF rate without surgery (70%-84%). had a positive outcome compared to 85% among those with normal GBEF

Arch Surg. 2009;144(2):180-187 Aliment Pharmacol Ther 2003 18, 167–174

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BILIARY DYSKINESIA BILIARY DYSKINESIA Children Long term follow children 41 with mean follow-up of 8.4 months. • Twenty-eight patients (68.3%) had symptom resolution. • 5 patients in the cohort had a normal ejection fraction of at least 35%, and all 5 noted relief of their symptoms after surgical intervention. • GBEF < 15%, pain upon CCK injection, and a family history of were not predictors of When present with pain and nausea, gallbladder emptying symptomatic resolution less than 15% has a positive predictive value of 93% and a negative predictive value of 81%. With multivariate analysis, only a gallbladder ejection fraction less than 15% could reliably predict symptom resolution when evaluated in all children irrespective of associated symptoms (EF 15%; P .0483).

J Pediatr Surg 2004; 39:813-816. Journal of Pediatric Surgery (2011) 46, 879–882

ORAL? PAIN DURING CCK LIPOMUL ADMINISTRATION? • 15 children • The mean GBEF after Lipomul challenge was 16.7% • Reproducible pain with CCK injection ±2.7%. during scintigraphy was a predictor of • The mean postoperative follow-up was 20 ± 5 months. successful postoperative outcome in a • Six months after the surgery, nine patients (60%) long-term prospective study in adults were asymptomatic, five (33%) had marked improvement of symptoms, and one (6%) was • Pain upon CCK injection was not unchanged. • At the time of latest follow-up, symptoms had associated with symptomatic relief in reappeared in two patients who had been children (odds ratio, 1.31; P = .440) asymptomatic at the 6-month visit (13%). • Seven patients (46%) remained asymptomatic, five (33%) had marked improvement but continued to have some persistent symptoms, and one (6%) was unchanged JPGN 2003 37:178–182 Journal of Pediatric Surgery (2011) 46, 879–882

REPRODUCIBILITY ABNORMAL GBEF 20 healthy volunteers • Abnormal GBEF is not only seen in dyskinesia – Reproducible – Other conditions

J Nucl Med. 1992;33(4):537-541. Gastroenterology 1991; 101: 786

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Reproducibel GBEF REPEAT HIDA?

• The mean GBEF value was reproducible • 12 children had more than 1 HIDA scan, between the 2 sequential studies in and 7 had at least 1 normal and 1 Controls (66.0% +/- 20.5% vs. 73.9% +/- abnormal result. 17.7%), BD group (24.4% +/- 22.3% vs. • Of these 7 patients, 5 had an abnormal 16.9% +/- 10.9%), and Chronic caluculous ejection fraction first followed by a normal cholecystitis (20.8% +/- 20.9% vs. 27.5% ejection fraction on the second test. +/- 34.5%) • Of those 7 patients, 6 improved with either surgery or conservative treatment.

Hepatogastro 2012; J Nucl Med 2004; 11:1872-1877. Journal of Pediatric Surgery (2006) 41, 1894

OTHER CONDITIONS OTHER CONDITIONS LONG TERM FOLLOW UP • 10 patients with abnormal GBEF did not have surgery because they had improvement of symptoms after treatment for an alternative diagnosis

• Diagnoses included gastroesophageal reflux, , , , and metastatic colon cancer.

• Five patients with peptic disease failed a trial of acid blockade but became asymptomatic after cholecystectomy. 4/10 improved after PPI Am Surg 1998; 64:493 4/10 improved after cholecystectomy Pediatr Surg Int (2011) 27:1307–1312

Biliary Dyskinesia PPI Children • Series of 75 children with BD after • Altered proximal GI physiology and surgery pathology could compromise biliary function. – 17 without improvement, • 7 were later diagnosed with Crohn’s disease, • PPI use may compete and downregulate CCK hiatal , and cyclic vomiting. receptors in gallbladder as chronic acid suppression with PPIs alkalinizes duodenal milieu, reduces CCK release from the and in turn causes high gastrin levels competing CCK function at receptors in the gallbladder. •J Pediatr Surg 43(6):1057–1059 Surg Endosc 2006; 20:1364–1367

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H PYLORI Biliary dyskinesia

• Tutelian et al. found a correlation in • Complete resolution of the symptoms of patients who had chronic atrophic biliary dyskinesia ranges from 66% to 80% • This range is very similar to that reported for gastritis with Helicobacterial infection the treatment of symptomatic cholelithiasis. in combination with chronic acalculous In the review by Fenster et al, the reported cholecystitis or dyskinesia. success rates ranged from 66% to 91%. • As such, laparoscopic cholecystectomy for biliary dyskinesia provides results that are similar to those associated with treatment of symptomatic cholelithiasis.

MORE RECOMMENDATIONS

• BEFORE ORDERING HIDA SCAN

• Clinical history compatible with biliary disease • Full work up – US, endoscopy – Treatment with PPI

• Biopsychosocial model.- It easy to do surgery • Consider cognitive-behavioral therapy • Beware of obesity and other psych problems • Repeat HIDA • Give correct expectations to the family

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