Contrast-Enhanced Harmonic Endoscopic Ultrasonography in the Differential Diagnosis of Gallbladder Wall Thickening

Differentiation of gallbladder (GB) carcinoma from benign GB wall thickening is challenging. The recent introduction of second-generation ultrasonic contrast agents has made contrast harmonic imaging with EUS possible. The aim of our study was to evaluate the utility of contrast-enhanced harmonic EUS (CH-EUS) for the differential diagnosis of GB wall thickening. Thirty-six consecutive patients with GB wall thickening imaged by CH-EUS and then underwent surgery were enrolled in this study. After the lesions were observed with conventional harmonic EUS (H-EUS), CH-EUS was performed with intravenous injection of 0.015 ml/kg of Sonazoid. Three reviewers with various levels of experience of EUS (Reviewer A: experienced endosonographer, B: EUS trainee, C: experienced gastroenterologist with expertise in transabdominal ultrasound but no EUS experience) were blinded to findings of recorded video of H-EUS and CH-EUS. The diagnostic accuracy of H-EUS and CH-EUS for malignant GB wall thickening was compared. Final diagnoses based on surgical histology were GB carcinoma in 16, cholecystitis in 11, adenomyomatosis in 6 and cholesterolosis in 3. Overall sensitivity, specificity and accuracy for diagnosing malignant GB wall thickening of H-EUS and CH-EUS were 83.3 versus 89.6, 65 versus 98 % (p < 0.001) and 73.1 versus 94.4 % (p < 0.001). The inter-observer agreement for H-EUS was moderate (kappa = 0.51), whereas that for CH-EUS was substantial (kappa = 0.77). The inhomogeneous enhanced pattern on CH-EUS was a strong predictive factor of malignant GB wall thickening. CH-EUS has the potential to improve the preoperative diagnostic accuracy and inter-observer agreement in the differential diagnosis of GB wall thickening.