Correlation Study between Multi-detector Spiral CT Perfusion Imaging and Clinicopathologic Factors and MVD and Expressions of VEGF in Esophageal Carcinoma
|Course||Pathology and Pathophysiology|
|Keywords||Esophageal carcinoma Tomography,X-ray computed Perfusion imaging Microvessel density Vascular endothelial growth factor|
Background and Purpose:Esophageal carcinoma is one of the common malignant tumors of digestive tract with poor prognosis. The cause of esophageal carcinoma is complicated. Because esophagus has no serosal layer,local invasion and lymph node metastasis is extremely commom,which are the main factors of affecting surgical treatment. So accurate judgement on tumor invasion and lymph node metastasis before the surgery and looking for its valuable index are aid to preoperative staging and prognostic evaluation for patients with esophageal cancer. Conventional CT scanning of esophageal carcinoma can better show the tumor location,form, violations of the surrounding circumstances, lymph node metastasis and distant metastasis,but can not reflect the blood perfusion status of tumor. CT perfusion imaging can display the changes in morphology and acquire the hemodynamic parameters of tumor vascular,including blood volume (BV), blood flow(BF), mean transit time(MTT), time to peak (TTP), peak enhancement index(PEI) and permeability surface(PS), which can evaluate the blood perfusion status of tumor tissue. Carcinoma is a vascular-dependent disease. The growth and metastasis of tumors can’t do without angiogenesis. Microvessel density (MVD) is now recognized as the gold standard for quantitative assessment of angiogenesis, reflects the strength of tumor microvessel. Tumor angiogenesis is controlled by a variety of angiogenesis regulatory factors, among which vascular endothelial growth factor(VEGF) is the most important one. This experiment aims to provide a basis for the preoperative clinical staging, choice of treatment and prognosis assessment in esophageal cancer by studying the correlation between the CT perfusion imaging parameters, MVD and expressions of VEGF, and clinical pathological parameters of esophageal carcinoma, such as tumor location, histological differentiation, tumor invasive depth, general pathologic types and lymph node metastasis.Materials and Methods:1. Clinical data:50 cases of specimen of esophageal carcinoma in the Henan Tumor Hospital were collected. All specimens were confirmed as esophageal squamous cell carcinoma and without distant metastasis. There are 36 male cases and 14 female cases. Age ranges from 44 to 80 years old,with an average age of 62.2. CT perfusion imaging,image post-processing and analysis:CT examination were performed with a GE Light Speed Plus 32 scanner.First, conventional chest CT scans were performed to determined the location and maximum levels of the esophageal carcinoma lesion, which were choosed as the target level of perfusion imaging. Contrast medium(Ioversol, dosage 50ml) was injected intravenously with high-pressure syringe at a race of 4 ml/s. Then start perfusion scan mode after 5 seconds delayed period, with 45s duration. The scan parameters were 120KV, 150mAs,5mm slice thickness. CT perfusion images will be sent to the GE image post-processing workstations(Advantage Windows 4.3,AW4.3) and processed by CT perfusion-3 body tumor software for data analysis. Descending aorta was selected to input artery. Region of interest(ROI) in the tumor was selected in the maximum levels and the most obvious enhancement levels, and the region was as large as possible. CT perfusion images post-processing can generate the lesions and the target artery time-density curve(TDC) and value of CT perfusion parameters, including BV, BF, MTT, PS, and with the pseudo-color image at the same time.3. Immunohistochemical analysis:The MVD and expression of VEGF were examined by means of SP immunohistochemical technique in 50 cases of esophageal carcinoma.4. All data were analysed with SPSS 13.0 statistical software. The enumeration data of two groups were compared using t test,comparison between multi-groups using analysis of variance. Bivariate correlation was analysed by Pearson correlation analysis, withα=0.05 for testing standards.Results:1. Among 50 cases of esophageal carcinoma,12 cases(24%) of tumors were located in the upper thoracic part,30 cases(60%) in the middle thoracic part,8 cases(16%) in the lower thoracic part. General pathologic types of esophageal carcinoma include 11 (22%) cases of medulla type,32(64%) cases of ulcerous type, 4(8%) cases of mushroom type and 3(6%) cases of sclerotic type. Histological differentiation of esophageal carcinoma include 8(16%) well-differentiated,28 (56%) moderately differentiated and 14(28%) poorly differentiated cases. Esophageal carcinoma invading the submucosa were found in 2(4%) cases, invading the muscular layer in 18(36%)cases,and invading the adventitia in 30(60%) cases. Esophageal carcinoma with lymph node metastasis were found in 24(48%) of 50 cases,and 26 (52%) cases without lymph node metastasis.2. CT perfusion parameters BF, BV, MTT, and PS of esophageal cancer revealed no significant relationship with tumor location,tumor invasive depth, histological differentiation, and general pathologic types (P>0.05). BF, BV, MTT of esophageal cancer revealed no significant relationship with lymph node metastasis(P>0.05). A significant difference (P<0.01)in the PS values was found between patients with or without lymph node metastasis.3. In 50 patients, the VEGF positive expression rate was 62%(31/50),and the negative expression rate was 38%(19/50). The MVD was 39.20±19.78 in VEGF positive tumors and 26.67±17.53 in VEGF negative tumors, and the difference was statistical significant(P<0.05).4. The average of CT perfusion parameters of esophageal carcinoma were as follows:BF values(116.71±47.59) ml/100 g/min、BV values(6.74±2.70) ml/100 g、MTT values(6.42±2.84)s、PS values(13.82±6.25) ml/100 g/min. The average count of MVD was 34.44±19.75. CT perfusion parameter BF values and MVD count were positively correlated(P<0.05). The correlation between BV, PS values and MVD count were more significant (P<0.01).There were no statistical correlation between MTT values and MVD count(P>0.05).5. The BF, BV, MTT, and PS values were (118.21±45.74) ml/100 g/min、(7.07±2.79) ml/100 g、(5.95±2.02)s、(15.33±6.20) ml/100 g/min in VEGF positive tumors and (114.27±51.67) ml/100 g/min、(6.20±2.44) ml/100 g、(7.19±3.76)s、(11.36±5.64) ml/100g/min in VEGF negative tumors. There were no statistical correlation between BF,BV,MTT values and VEGF expression(P>0.05). The PS value and VEGF expression were positively correlated(P<0.05).Conclusion:1. Multi-detector spiral CT perfusion imaging can to a certain extent reflect the clinicopathologic characteristics of esophageal carcinoma. PS value is the most valuable CT perfusion imaging parameter.2. PS values of esophageal carcinoma with lymph node metastasis were significantly higher than those of without lymph node metastasis, which is helpful to evaluate the possibility of lymph node metastasis and provide the functional evidences of preoperative diagnosis of lymph node metastasis.3. CT perfusion parameters can reflect not only the angiogenesis of esophageal carcinoma of the MVD,but also the expression of VEGF, indicating that CT perfusion parameters BV, BF and PS can be used as an in vivo assessment of tumor angiogenesis.