Management of gallbladder dyskinesia: patient outcomes following positive 99mtechnetium (Tc)-labelled hepatic iminodiacetic acid (HIDA) scintigraphy with cholecystokinin (CCK) provocation and laparoscopic cholecystectomy
Introduction
Typical biliary pain is a common source of surgical referral, both in the outpatient clinic and during the acute surgical take, as 10–15% of people in the adult Western world develop gallstones. Between 2003–2005, UK Hospital Episode Statistics' data showed that 25,743 patients were admitted as an emergency with acute gallbladder disease.1 The standard imaging investigation for patients presenting with biliary pain is the transabdominal ultrasound.2 In the event of a normal ultrasound, patients may be misdiagnosed as having “non-specific abdominal pain” despite the occurrence of classical biliary symptoms. The diagnosis of a “non-functioning” or “dyskinetic” gallbladder must be considered in these patients, a functional condition of the biliary system that has been reported dating as far back as 1956.3, 4
Although gallbladder dyskinesia (GD) has been recognized as a cause of biliary pain for over five decades,4 the Rome consensus process for functional gastrointestinal disorders (FGIDs) has focused recent attention on this important clinical entity by identifying clear diagnostic criteria for GD. GD is defined by the Rome III Committee as symptomatic episodes of pain in the epigastrium and/or right upper quadrant lasting 30 min or more, with pain-free intervals; symptoms having occurred on one or more occasion in the previous 12 months; the pain is steady and disrupts daily activities or requires consultation with a physician; and there is no evidence of structural abnormalities to explain the symptoms, i.e., normal ultrasound of biliary tree and normal gastroscopy. Prior to any invasive intervention, the Rome III recommendation is that 99mtechnetium (Tc)-labelled hepatic iminodiacetic acid analogue (HIDA) scintigraphy with cholecystokinin (CCK) provocation is conducted, where available, to objectively assess gallbladder emptying.5, 6, 7
The mechanism of pain in patients with GD remains poorly understood, and the association of GD and cholecystitis remains a “chicken-and-egg” scenario. Velanovich8 suggested that a defect in motility of the gallbladder results in crystal formation within gallbladder bile, which becomes entrapped in the mucosal surface of the gallbladder, and the consequent inflammation and dysmotility leads to gallbladder stretching and pain. Yap et al.9 and others6 have suggested that the mechanism of pain might be due to obstruction leading to distension and inflammation of the gallbladder. The obstruction may be mechanical (e.g., due to a small cystic duct) or functional, due to incoordination between gallbladder contraction and relaxation of either the cystic duct or the sphincter of Oddi (due to increased resistance or tone).
The functional imaging test of choice to assess gallbladder motility and emptying is HIDA scintigraphy using a 99mTc-labelled bile salt analogue.10 There are several bile acid analogues that can be labelled with technetium to enable single-photon emission imaging with a gamma camera, but the currently preferred agent in most institutions is Mebrofenin (3-bromo-2,4,6-trimethylphenyl-carbomyl-methyl-imino-diacetic acid; Bracco Diagnostics; Princeton, NJ, USA) because of its high hepatic extraction efficiency. The HIDA radiopharmaceutical is extracted by hepatocytes and excreted and cleared through the biliary system in a similar fashion to bilirubin, effectively demonstrating the formation and flow of bile.10 Provocation of gallbladder emptying with a synthetic octapeptide analogue of cholecystokinin (CCK; sincalide for injection; Kinevac, Bracco Diagnostics) has been recognized as the preferred and most standardized method to calculate the gallbladder ejection fraction (GB-EF) to diagnose GD.11 Alternative methods are available, including the oral ingestion of a standard fatty meal or a proprietary high-calorific fatty acid emulsion. Although these techniques are less well validated, they are gaining increasing acceptability in routine clinical practice, especially considering recent difficulties with sincalide availability.12
There are few long-term clinical outcome studies of GD following laparoscopic cholecystectomy (LC) in a UK patient population. To the authors' knowledge, this study represents the largest series to date in a UK population, where clinical outcomes have been assessed following LC in patients diagnosed with GD with abnormal CCK provocation HIDA scintigraphy.
Section snippets
Patient selection
Patients with typical biliary symptoms, a negative ultrasound, and provocation HIDA scintigraphy were identified both from a prospectively maintained database and by a retrospective keyword search of the hospital electronic records. Since the publication of a pilot study in July 2007,13 it has been the practice at St James University Hospital to offer LC to those patients diagnosed with GD with a positive HIDA scintigram. All patients fulfilling these criteria between July 2007 and October 2012
Patient population
Of the 100 patients included in the study, the median age was 44 years (range 17–73 years), and 80% of subjects were female. Ultrasound showed no gallstones in all patients, but five had an incidental abnormality: adenomyomatosis in one and polyps in four. The median follow-up was 12 months (range 2–80 months).
Outcomes following LC
Ninety-five percent of patients were happy with the decision to proceed with LC (95/100). Eighty-four percent had overall improvement, with 53% reporting that their symptoms were “very
Discussion
GD is a challenging clinical condition to diagnose and treat successfully. Several series have been published advocating LC as a treatment for GD, mainly in North American patient cohorts, with symptomatic resolution or improvement ranging from 66–98%.9, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28 In the most recent published series, early postoperative relief in patients with GD was 78%, and long-term improvement, at a mean duration of 42 months, was 66%.29 To the authors'
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