Gallbladder wall thickening identified on trans-abdominalultrasound is a relatively common finding that can be dueto common biliary pathologies such as cholecystitis, gall-bladder carcinoma, and adenomyomatosis, while systemicdisease and extracholecystic inflammation may also distortgallbladder morphology [1]. In many cases, ultrasoundimaging combined with the clinical history will suffice;however, for some patients, further imaging studies arerequired in order to accurately distinguish benign andmalignant pathologies. At the extremes, the patient with asuspected gallbladder cancer requires urgent referral to aspecialist hepatobiliary surgeon whereas the elderly, frailpatient with adenomyomatosis may simply be reassured.Cross-sectional imaging with computed tomography(CT) or magnetic resonance imaging (MRI) can providevaluable additional information concerning the etiology ofgallbladder wall thickening. However, there are surpris-ingly few studies that have addressed these modalities inthe context of gallbladder wall thickening [2–5], eventhough current cross-sectional imaging modalities canaccurately differentiate benign from malignant pathologiesin the majority of cases. When these techniques revealequivocal results, endoscopic ultrasound (EUS) may beconsidered. Despite its widespread use in the evaluation ofpancreatobiliary disease, it has not yet gained widespreaduse in evaluating the gallbladder [6, 7]. In the setting of athickened gallbladder wall, Kim and colleagues reported itto be of value with a wall thickness[10 mm and reducedinternal echogenicity being predictive of malignancy [8].In this issue of Digestive Diseases and Sciences, Imazuet al. [9] evaluated contrast-enhanced harmonic endoscopicultrasonography (CH-EUS) using a second-generation con-trast agent consisting of perfluorobutane microspheres(Sonazoid) in thediagnosis ofpatients exhibitinggallbladderwall thickening. The group examined 36 patients withequivocal conventional ultrasound and cross-sectional imag-ing in whom surgery was performed to provide histopatho-logic confirmation. The performance characteristics(sensitivity, specificity, accuracy, positive predictive value,negativepredictivevalue,andareaunderthereceiveroperatorcurve) of CH-EUS were 89.6, 98, 94.4, 97.7, 92.2, and 0.94,respectively, superior to conventional EUS in each case. Theauthors assessed inter-observer variation by comparingassessments made by an experienced endosonographer, atrainee EUS operator, and an experienced gastroenterologist,demonstrating an improvement in J score from 0.51 (mod-erate)to0.77(substantial)withtheadditionofSonazoid.TheyalsoidentifiedthataninhomogeneousenhancementpatternonCH-EUS,andawallthickness[12 mmwithoutcontrastwerestrongly predictive of a malignant etiology.CH-EUS is based on harmonic imaging, which exploitsthe nonlinear propagation of acoustic signals through bio-logical tissues, with secondary signals generated by thetissue creating high-resolution images. The use of contrastprovides the key advantage of enabling visualization of themicrovasculature in real time [9].Although this is the first series evaluating CH-EUS inassessing gallbladder wall thickness, the technique hasbeen used with success in the evaluation of gallbladder [10,11] polyps and pancreatic lesions [12].
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