Role of Low-Mechanical Index CEUS in the Differentiation between Low and High Grade Bladder Carcinoma: a Pilot Study

We read with great interest the article by Drudi et al. about the role of contrast-enhanced ultrasound (CEUS) in the differentiation between low and high grade bladder carcinoma, recently published in Ultraschall in der Medizin [1].

The authors reported that the sensitivity and specificity of CEUS were 90.9 % and 85.7 %, respectively. And the sensitivity and specificity of CEUS using Time-intensity curves (TICs) enabled was 95.4 % and 85.7 %. And our data agree with such a result (unpublished data).

In the study by Drudi et al. a slowly declining curve (shape B) indicating low-grade carcinoma and a rapidly declining curve (shape C) indicating high-grade carcinoma. We recently examined ninety-six patients with ninety-six bladder lesions, including 55 high grade urothelial carcinoma and 41 low grade urothelial carcinoma by CEUS. QLAB quantification software (Philips medical system, Bothell, WA, USA) were used. The arrival time (AT), peak intensity (PI), time to peak intensity (TTP) and washout time (WT) with the tumors were extracted by the off-line software. Our result are shown in [Table 1]. There were no significant differences in the AT,TTP between high and low grade bladder tumors (P > 0.05). The PI of high grade tumors are greater than that of low grade tumors, which is consistent with Drudi et al’s results, but the WT of low grade tumors were less than that of high grade tumors (P < 0.05), which is completely different from their results. Our study found that 93 % (51 / 55) of high grade bladder tumors showed fast wash-in and slow wash-out enhancement patterns ([Fig. 1]) and 85 % (35 / 41) of low grade bladder lesions showed fast wash-in and fast wash-out enhancement patterns ([Fig. 2]).

Table 1 Contrast parameters of high and low grade urothelial carcinoma (mean ± SD). (AT = arrival time; TTP = time to peak; PI = peak intensity; WT = washout time). TIC parameters HG LG P Value AT (s) 21.13 ± 1.76 22.44 ± 1.34 0.374 PI (dB) 20.85 ± 12.31 14.87 ± 9.24 0.005 TTP(s) 30.32 ± 2.41 28.06 ± 2.23 0.386 WT(s) 35.37 ± 9.34 21.17 ± 8.37 0.002

Fig. 1 a 58-year-old man with high grade bladder tumor. Time-intensity curve shows fast wash-in and slow wash-out, and higher PI (peak intensity). b Surgical specimen confirming high grade bladder tumor (hematoxylineosin original magnification ×  40).

Fig. 2 a 60-year-old woman with low grade bladder tumor. Time-intensity curve shows fast wash-in and fast wash-out, and lower PI (peak intensity). b Surgical specimen confirming low grade bladder tumor (hematoxylineosin original magnification ×  40).

Several differences between Drudi et al’s study and ours should be addressed. Firstly, Drudi et al’s sonogrphic examination was performed on Technos Mpx, Mylab 70 V_x Gold (Esaote, Genova, Italy), and Toshiba Apliova (Osaka, Japan) using a 2-MHz multi-frequency broadband convex transducer. In our study, both US and CEUS were performed with PhilipIU22 (Philips royal electronic corporation, Holland) system with a 1.0 – 6.0 MHz probe, the contrast-specific sonographic imaging modes were PI (pulse inversion) and PM (power modulation) at a mechanical index of 0.05. Secondly, the dose of Sonovue in the two studies is differently. Drudi et al’s study dose was 2.4 ml, and ours was 1.2 ml, the dose we use was based on our research team’s clinical experience, we found that when a bolus of 2.4 ml contrast agent was injected, the perfusion of both high and low grade bladder lesions are saturated, and there is no Significant difference on PI (peak intensity) between the two kind of tumors. Thirdly, 36 Italian patients in Drudi et al’s study were recruited, and 96 Chinese patients were included in our study. It is generally accepted that bladder urothelial carcinoma incidence is affected by environment factors such as the habits of the nation.

In conclusion, we agree with Drudi et al. that CEUS is a reliable noninvasive method for differentiating low and high grade bladder carcinomas. However, to the best of our knowledge, that paper was the first regarding the use of CEUS for bladder cancer characterization. As only limited data are available, it might be inappropriate that we applies these enhancement patterns to the worldwide population, which has different incidence of bladder carcinoma because of racial, biological, and clinical differences. In our opinion, Further studies involving larger patient populations from different places to confirm these preliminary results is expected.

Reference

• 1 Drudi F M, Cantisani V, Liberatore M et al. Role of low-mechanical index CEUS in the differentiation between low and high grade bladder carcinoma: a pilot study.  Ultraschall in Med. 2010;  31 589-595