Sentinel node detection method using contrast-enhanced ultrasonography with sonazoid in breast cancer: preliminary clinical study.

This study aimed to evaluate the usefulness of sentinel lymph node (SLN) detection in breast cancer using contrast-enhanced ultrasonography (CEUS) with subareolar Sonazoid injection. The subjects were 20 breast cancer patients. General anesthesia was induced and 2 mL of Sonazoid was injected subareolarly. After massage of the injection site, the axillary area was observed transdermally using coded phase inversion harmonic ultrasonography with mechanical indices of 0.15 to 0.19. When contrast-enhanced lymph nodes (LNs) were seen, they were defined as CE-SLN. Two other SLN detection methods, the gamma-probe-guided and dye-guided methods, were performed together. We evaluated the SLNs detected by each method to determine if they corresponded with each other and calculated the SLN detection rate. After the SLNs were resected, pathologic examinations were done. The SLN detection rate of the CEUS-guided method, the dye-guided method and the gamma-probe-guided method were 70%, 75% and 100%, respectively. There was no statistically significant difference in these rates between the CEUS-guided and dye-guided methods (p = 0.99) but the CEUS-guided method showed a significantly lower rate than the gamma-probe-guided method (p = 0.020), and dye-guided method also showed a significantly lower rate than the gamma-probe-guided method (p = 0.047). The number of CE-SLNs was 1 or 2 (average 1.1) and each took 2 to 20 (average 5.3) min to detect. The CE-SLNs corresponded grossly with SLNs detected by the gamma-probe-guided and dye-guided methods. The pathologic results indicated no metastasis from the resected SLNs in 15 of 20 cases. However, the CEUS-guided method detected 12 cases of these 15 and CE-SLNs were detected in two of the remaining five metastasis cases. In summary, in breast cancer patients, after subareolar injection of Sonazoid, contrast-enhanced LNs were observed in real time with ultrasonography. In an initial clinical study of 20 cases, the detection rate of the CEUS-guided method was less than that of the gamma-probe-guided method. It is suggested that the CEUS-guided method using Sonazoid may, with some improvements, be a useful new modality for sentinel node identification.

Sentinel node detection in breast cancer using contrast-enhanced sonography with 25% albumin--Initial clinical experience.

PURPOSE: To determine the clinical usefulness of a sentinel lymph node (SLN) identification technique using contrast-enhanced sonography (CEUS) with 25% albumin. METHODS: The subjects were 23 women with breast cancer. Each was injected subcutaneously with 5 ml of 25% albumin solution as a negative contrast agent directly superficial to the breast tumor. The area was massaged, and the inferior axillary hairline was examined continuously using gray-scale sonography with a 7.5- or 10-MHz transducer. Any contrast-enhanced lymph node was considered a CEUS-detected SLN, was differentiated from other level I and II nodes, and was resected and pathologically assessed. RESULTS: In all 23 patients, 1 or 2 CEUS-detected SLNs (mean, 1.3 SLNs) were identified. Their sizes ranged from 5 mm to 25 mm (mean, 11.3 mm), and their depths (from the skin surface) ranged from 5mm to 20 mm (mean, 12.6 mm). Pathologic examination revealed a metastasis in 5 of the 23 patients, all in CEUS-detected SLNs. CONCLUSION: In a clinical study using CEUS with 25% albumin, contrast-enhanced nodes were identified in all subjects. The pathologic findings suggested that any metastatic nodes observed were SLNs, indicating that this technique may represent a new modality for SLN identification.

New method of sentinel node detection using a combination of contrast-enhanced ultrasound and dye guidance: an animal study.

PURPOSE: To determine whether a combination of contrast-enhanced ultrasound-guided methods and dye-guided methods can identify sentinel lymph nodes in animals. METHODS: Seven pigs were put under general anesthesia and injected subcutaneously in the neck: three with 2 ml saline and four with 2 ml fluid comprising 0.4 ml 5% patent blue violet solution and 1.6 ml of hydroxyethylated starch (Salinhes) solution (PB + HS). The regional lymph nodes were observed by ultrasound; blue-stained regional lymph nodes found after the skin was cut were situated as ultrasound had shown they would be. RESULTS: The regional lymph nodes of the pigs given saline were unchanged, but in the pigs receiving PB + HS, the echo level in the lymph nodes nearest the injection site was altered, producing a clear contrast with the surrounding tissues. The area of the relevant regional lymph node in each PB + HS-injected pig increased significantly (t-test, P < 0.01; from 25.7, 39.6, 9.36, 70.2 mm(2), and mean, 36.2 mm(2); to 50.7, 65.5, 21.1, 98.3 mm(2), and mean, 58.9 mm(2), respectively). These enlarged regional lymph nodes were easily found by contrast-enhanced ultrasonography. When excised under ultrasound guidance, all were stained blue, indicating that they were sentinel lymph nodes. CONCLUSION: These results suggest that this combination of contrast-enhanced ultrasound-guided and dye-guided methods warrants use as a quick, simple procedure for detecting sentinel lymph nodes.

Study of the automated breast tumor extraction using 3D ultrasound imaging: The usefulness of depth-width ratio and surface-volume index.

We applied quantitative parameters in three-dimensional ultrasonic images to distinguish benign from malignant breast tumors in 29 benign cases including 8 cysts and 21 fibroadenomas, and 32 malignant cases including 23 ductal carcinomas, 2 special types of carcinoma, 1 malignant lymphoma and 6 others. This procedure involved simultaneously acquiring video data from real-time ultrasonic images and recording the original position and orientation of the probe. Both sets of data were fed directly into a desktop computer. Fuzzy reasoning and relaxation techniques were use to automatedly extract the shape of the tumor and render it in three dimensions. We then evaluated three parameters: 2D-D/W, the so-called depth-width ratio measured in B-mode images: 3D-D/W; and the S/V index ([surface area](3)/36π [volume](2)) calculated from the three-dimensional volume extracted with this system. All three parameters were significantly higher in the malignant group (averages: 0.81, 0.64, and 11.3, respectively) than in the benign group (averages: 0.62, 0.47, and 3.78, respectively). All three parameters were thus found to be useful in differentiating the two groups.

New method of sentinel node identification with ultrasonography using albumin as contrast agent: a study in pigs.

The purpose of our study was to verify in animals the possibility of using albumin-enhanced ultrasonography as a modality for sentinel node detection. The nine pigs were injected subcutaneously in the neck with albumin, five with 5% solution and four with 25% solution, and then the regional lymph nodes were observed over time. It was found that, where the 5% solution had been injected, the lymph nodes showed no change, but where the 25% solution had been used, a high echo 1 to 5 mm in size was seen at the hilus of the nearest lymph node. Examination of the excised pathologic specimens of lymph nodes demonstrated that this echo was due to albumin accumulated in the efferent lymphatics. This finding suggested that this technique of ultrasonography using albumin as a contrast agent was an effective new method of identifying sentinel nodes.

Anticarcinogenic effects of isoflavones may be mediated by genistein in mouse mammary tumor virus-induced breast cancer.

Isoflavones are known to exert anticancer effects. These effects were examined using two isoflavones, biochanin A and daidzein, in a mouse mammary tumor virus (MMTV)-induced spontaneous breast cancer model. Emphasis was placed on isoflavone metabolism by the intestinal microflora and changes in estrogen levels. Germ-free (Gf) mice and their conventionalized (Cv) counterparts were assigned to three diet groups: (1) control diet, (2) biochanin A and (3) daidzein. In all groups, urine was collected from virgin female mice to analyze isoflavone metabolism by high performance liquid chromatography. These studies revealed changes of biochanin A into genistein, and of daidzein into equol, which were accelerated in the Cv animals. However, the Gf mice could not transform biochanin A into genistein, or daidzein into equol. Estrogen levels in the control and daidzein diet groups were lower in the Gf mice than in the Cv mice. The biochanin A group showed no differences in estrogen levels between the Cv and Gf animals. Four-week-old male and female animals were paired in the Gf and Cv groups. The female animals delivered and lactated repeatedly and were observed for the development of mammary cancer by palpation, twice weekly, until 15 months of age. The Cv mice showed a significantly lower incidence of breast cancer in the biochanin A diet group than in the control or daidzein groups (p < 0.05). These results suggest that the anticarcinogenic effects in this system might be produced not by daidzein or equol, but by biochanin A and/or genistein. In the Gf animals, the incidence of breast cancer was significantly higher in the biochanin A group than in the control group (p < 0.05), probably due to the increased level of estradiol in the former group. The biochanin A group tended to have a higher incidence of breast cancer than the daidzein group in the Gf group, although no significant differences were noted. Thus, no anticarcinogenic effect was produced by biochanin A alone in the Gf mice. In view of the results presented, genistein derived from biochanin A following metabolic processes in the intestinal microflora most likely acts as an inhibitor in breast carcinogenesis; biochanin A is most likely a precursor of genistein.