| 1. ObjectivesThe morbidity and mortality of gastric carcinoma is high worldwide. The biological behaviors of malignant tumor are an essential factor for predicting the prognosis and selecting the therapeutic strategy. In this study, the double contrast-enhanced ultrasonography (DCEUS), in which an oral ultrasonic contrast agent (OCUS) is combined with an intravenous contrast agent, was used to assess the angiogenesis, pathological classification, infiltration and metastasis of gastric carcinoma. The aim of this study was to explore a novel method for preoperative evaluating the biological behaviors of gastric carcinoma safely, effectively, accurately and reliably.2. Materials and Methods2.1SubjectsPatients with gastric carcinoma confirmed by endoscopic biopsy were enrolled in this study according to the inclusion and exclusion criteria. DCEUS was performed for all of the subjects. The qualitative and quantitative results of DCEUS were used to assess the gastric cancer by compared with the pathological, immunohistochemical and clinical findings. 2.2Double contrast-enhanced ultrasonographyAt first step of DCEUS, the stomach, liver, gallbladder, spleen, pancreas, kidney and pelvic cavity was scanned by routine ultrasonography. The distal esophagus and the cardia of all patients were studied in real time B-mode using conventional tissue settings while the patients ingested the oral agent. Then the remaining parts of the stomach and the duodenal bulb were examined in turn, with the patient in the supine and both decubitus positions to facilitate complete filling and visualization of the lesion. By using a continuous multi-sectional scanning method, the entire stomach and duodenal bulb were examined in real time to identify a suspected lesion, and then a longitudinal view of the lesion was selected for following contrast imaging examination. Afterwards, dynamic real-time contrast-enhanced ultrasonography (CEUS) was performed in a selected imaging section after the administration of2.4mL of SonoVue as a bolus via a peripheral intravenous cannula followed by a10mL saline flush. The entire video sequence was stored on magnetic optical disks for analysis. The liver and kidney was scanned again before finishing the DCEUS.2.3Qualitative and quantitative analysis of DCEUSThe images acquisition of DCEUS for all of the cases was retrospective analyzed by different independent radiologists. The size, location, shape, infiltrated degree, intensive features and surrounding tissue of gastric cancer were characterized during the qualitative analysis by OCUS and DCEUS, and the results of these two modes were compared each other. The intensity of gastric cancer tissues and normal gastric wall were quantitatively analyzed by drawing the region of interesting and compared with the pathology.2.4Clinicopathological analysisThe clinical data of all cases were collected. The pathological, immunohistochemical and AB-PAS stain were performed for the enrolled patients.3. Results3.1Quantitative results for the angiogenesis of gastric carcinomaBy compared the parameters of DCEUS between gastric cancer tissue and normal gastric wall, significant differences were obtained for basal intensity (BI), peak intensity (PI), enhanced intensity (EI) and wash-in time (WIT)(P value were0.000,0.007,0.000and0.022respectively). However, the differences of arrival time (AT) and time to peak (TTP) between two kinds of tissues were not significant (P value were0.855and0.062).There was a strong positive linear correlation between El and microvessel density (MVD) of gastric cancer tissue (r=0.893). A moderate positive linear correlation between PI and MVD (r=0.757), moderate negative linear correlation between BI and MVD (r=-0.540) and mild negative linear correlation between WIT and MVD (r=-0.305) were demonstrated in this study. By comparing with VEGF, the mild positive correlation for El (rs=0.434), mild negative correlation for BI (rs=-0.422) and poor positive correlation for PI (rs=0.260) were obtained.The matching effect between El and MVD was associated with the size and location of the lesions. The lesions larger than5cm were superior to that less than5cm for the correlation analysis. The descending order of matching effect according to the lesion location was as follow:whole stomach, body, antrum, cardiac and fundus.3.2Prediction of pathological classification of advanced gastric carcinomaThe accuracy for assessing the Borrmann classification of advanced gastric cancer was79.03%by OCUS and91.94%by DCEUS. There was a significant difference between these two modes (χ2=4.900, P=0.027). The classification of8cases (12.90%) was corrected after combined with intravenous contrast ultrasound.For Lauren classification,88.89%patients with diffused type gastric cancer appeared heterogeneous enhancement by DCEUS, but88.57%patients with intestinal type appeared homogeneous enhancement. There was a significant difference of the enhanced pattern between these two subtypes (χ2=36.927, P=0.000). The sensitivity, specificity, positive predicted value, negative predicted value and Youden index of DCEUS for assessing diffused type by heterogeneous enhancement were88.89%,88.57%,85.71%,91.18%and0.77respectively.There were good intra-observer and inter-observer reliability of DCESU for assessing Borrmann and Lauren classification of gastric carcinoma.3.3Evaluation for infiltration and metastasis of gastric carcinomaThe accuracy for assessing the T stage of gastric cancer was70.45%by OCUS and79.55%by DCEUS. There was a significant difference between these two modes (χ2=4.900, P=0.027). The staging of9cases (10.23%) was corrected after combined with intravenous contrast ultrasound, especially for the T4stage which invades the serosa. There were good intra-observer and inter-observer reliability of DCESU for assessing T stage of gastric carcinoma.The accuracy for assessing the lymph nodes metastasis of gastric cancer was61.36%by OCUS and65.91%by DCEUS. There was not a significant difference between these two modes (/=2.250, P＝0.134).The detect rate for liver metastasis by DCEUS (87.18%) was higher than that by OCUS (54.70%) significantly (χ2=36.026, P=0.000). 4. ConclusionsThe morphological features and blood perfusion of gastric carcinoma could be assessed accurately by preoperative DCEUS with qualitative and quantitative analysis, which is useful for evaluating the angiogenesis, pathological classification, infiltration and metastasis of gastric carcinoma. DCEUS is promised to be a novel method to assess the biological behaviors of gastric cancer safely, effectively, accurately and reliably. |
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