Clinical utility of three-dimensional contrast-enhanced ultrasound in the differentiation between noninvasive and invasive neoplasms of urinary bladder

Abstract

Objectives

The purpose of this study was to evaluate the effectiveness of three-dimensional contrast-enhanced ultrasound in differentiating invasive and noninvasive neoplasms of urinary bladder.

Methods

A total of 60 lesions in 60 consecutive patients with bladder tumors received three dimensional ultrasonography, low acoustic power contrast enhanced ultrasonography and low acoustic power three-dimensional contrast-enhanced ultrasound examination. The IU22 ultrasound scanner and a volume transducer were used and the ultrasound contrast agent was SonoVue. The contrast-specific sonographic imaging modes were PI (pulse inversion) and PM (power modulation). The three dimensional ultrasonography, contrast enhanced ultrasonography, and three-dimensional contrast-enhanced ultrasound images were independently reviewed by two readers who were not in the images acquisition. Images were analyzed off-site. A level of confidence in the diagnosis of tumor invasion of the muscle layer was assigned on a 5° scale. Receiver operating characteristic analysis was used to assess overall confidence in the diagnosis of muscle invasion by tumor. Kappa values were used to assess inter-readers agreement. Histologic diagnosis was obtained for all patients.

Results

Final pathologic staging revealed 44 noninvasive tumors and 16 invasive tumors. Three-dimensional contrast-enhanced ultrasound depicted all 16 muscle-invasive tumors. The diagnostic performance of three-dimensional contrast-enhanced ultrasound was better than those of three dimensional ultrasonography and contrast enhanced ultrasonography. The receiver operating characteristic curves were 0.976 and 0.967 for three-dimensional contrast-enhanced ultrasound, those for three dimensional ultrasonography were 0.881 and 0.869, those for contrast enhanced ultrasonography were 0.927 and 0.929. The kappa values in the three dimensional ultrasonography, contrast enhanced ultrasonography and three-dimensional contrast-enhanced ultrasound for inter-reader agreements were 0.717, 0.794 and 0.914.

Conclusion

Three-dimensional contrast-enhanced ultrasound imaging, with contrast-enhanced spatial visualization is clinical useful for differentiating invasive and noninvasive neoplasms of urinary bladder objectively.

Introduction

Bladder carcinoma is the most common malignancy of the urinary tact. In 2006 in Europe, an estimated 104 400 incident cases of bladder cancer were diagnosed (82 800 in men and 21 600 in women), which represents 6.6% of total cancers in men and 2.1% in women. In men, bladder cancer was the fourth most common cancer [1]. The treatment of bladder cancer is dependent on the grade and stage. Based on the updated European Association of Urology guidelines, for non-muscle-invasive urothelial carcinoma of the bladder, conservatively local endoscopic resection with or without adjuvant administration of chemotherapeutic agents can be managed, but the use of radical cystectomy and urinary diversion are required for patients with muscle-invasive tumor [2], [3]. Therefore, a precise staging of a bladder carcinoma is very important to determine the treatment planning and to predict the outcome of treatment.

Computed tomography (CT), magnetic resonance image (MRI) and transabdominal or transurethral ultrasonography (US) have been extensively used previously for identification and staging of bladder neoplasms, but none of these techniques is sufficiently accurate [4], [5], [6]. Conventional cystoscopy is considered the gold standard for bladder tumor evaluation. However, this modality has a limitation for the evaluation of extravesical infiltration and its invasiveness may cause urinary sepsis or iatrogenic bladder injury [7], [8], [9]. The use of multidetector CT (MDCT) imaging is recommend for evaluation of extravesical tumor infiltration and the presence of metastasis, compared with flexible cystoscopy, MDCT is approximately 90% sensitive in bladder tumor detection and facilitates differential diagnosis of tumors spreading in the perivesical tissues and tumors confined within the bladder wall [10]. However, CT cannot show individual layers of the bladder wall [11], and therefore cannot be used for reliable estimation of the depth of tumor invasion [12]. MRI with dynamic contrast administration is effective for the differentiation of noninvasive ones from invasive tumors [13]. However, over staging is a common problem because of hyperemia mimicking tumor spread and acute edema [13], [14].

Ultrasonograph (US) is considered the first choice and safe technique for bladder cancer as it is noninvasive and easy to perform. The use of two dimensional US (2D US) is limited by the subjectivity and expertise of the examiner. The use of three dimensional US (3D US) can provide a direct 3D impression of pathological structures and allow a systematic visualization of the different layers of the bladder wall. The use of 3D US increases objectivity and provides examiners with an opportunity to view findings in multiple planes and increase the rate of accurate diagnosis [15]. Contrast enhanced ultrasound (CEUS) is effective in evaluating tissue vascularity and has been widely used in different organs and lesions in recent years, for overcoming some of the limitations of conventional US and Doppler in tumor staging and lesion characterization [16], [17]. A new study showed that CE US is better than convectional US for differentiating noninvasive and invasive neoplasms of the urinary bladder [18]. Three-dimensional contrast-enhanced ultrasound (3D CE US) imaging is a new medical imaging technique that allows the images to be displayed spatially at different visual angles and uses reflections of microbubbles to clearly depict blood vessels. Although 3D CE US imaging has recently been as a means of clinical diagnosis [19], [20], to the best of our knowledge, no previous investigations have been performed to differentiating urinary bladder tumor staging. The aim of this study was to investigate the effectiveness of 3D CE US in differentiating noninvasive and invasive neoplasms of urinary bladder.