The Study Of Infiltrating Growth Characteristics Of Breast Carcinoma With Digital Virtual Three Dimensional Reconstruction And Whole-breast Sections

Breast cancer is one of the most common malignant tumors harming women's health, with increasing trend year by year. Because of the anatomical characteristics, breast cancer is regarded as an emphasis in the study of malignant tumors. Surgery has still been the main treatment for breast cancer at present. Deeper recognition of the biological characteristics of breast cancer has led to a conception that breast cancer is a systemic disease at the beginning. And breast conserving therapy (BCT) has been regarded as the first choice for stage I-II invasive breast cancer recently. In developed countries, more than 50 percent of breast cancer patients are treated with BCT. But there still exist some problems in breast conserving surgery, like local recurrence, the postoperative shape of breasts, the economic problem from postoperative chemotherapy, etc. All these ascribe to the insufficient study of the spatial structure of the tumor. Adequate excision extent in breast conserving surgery has not been well solved clinically. There has been no good standard evaluation for excision extent now, and it is evaluated just according to doctors' experiences, which lacks theoretical evidence. Neoadjuvant chemotherapy has the effect of reducing clinical pathological stage of breast cancer and can raise the rate of BCT. But there are few studies on the characteristics of tumor and its infiltration after chemotherapy. With the progress of visible human project (VHP), digital virtual technique has been used widely. Virtual modeling surgery, navigationg surgery and tele-control surgery have been applied to clinical research and practice gradually. In breast surgery, it is necessary to combine three-dimensional visualization with the study of breast cancer. Utilizing digital virtual technique to navigate surgery can help improve and perfect BCT and evaluate more accurately the excision margin. In this study we produced successfully computer-assisted thin sections anatomy and three dimensional (3D) reconstruction technique to reconstruct human breast cancer in whole breast specimens to observe the 3D growth characteristics of breast cancer and the contrast with 3D-CT reconstruction images, with an attempt of providing evidences for improving accuracy of imageology, and observing infiltrating features of breast cancer using whole breast sections technique, finally to provide theoretical evidences for evaluation of resection margin for BCT.Methods and results:1. Human breast cancer 3D reconstruction to observe the growth and morphological characteristics of the tumorAll whole breast specimens were pathologically diagnosed by core biopsy before surgery. First, every specimen was fixed by 10% formalin, embedded by gelatine solution and frozen at low temperature respectively. Then each specimen was cut into 0.2mm slices at -20～-25℃and imaging of each slice was acquired simultaneously by a 11 million pixels digital camera. The serial and clear images of thin sections anatomy were acquired, and many structures could be observed in detail. By means of several transformations of image data format, pinpointed by Photoshop 7.0, the breast structures were dissected. We drew the outline of the breast margin, skin, glandular tissue, tumor, blood vessel and so on, and then the 3D reconstruction of the dissected breast structures were made including the volume and surface measurement of some structures by 3D DOCTOR1.0 to show 3D manifestation.A total of 17 data sets of serial thin section anatomy were acquired. By the observation of thin sections anatomy and 3D reconstruction's characteristics, each slice could show the structures clearly, such as skin, glandular tissue, subcutaneous tissue, tumor and so on. We could distinguish the border between tumor and normal glandular tissue in the whole-breast sections. In different sections, the shapes of the tumors were different, round or irregular. The observation of the interior of the tumor showed the shade was also different with glandular tissue, which was gloomy than normal glandular shade. Parenchymatous tissue of tumor was also not well-distributed. Some areas were pyknotic, and other areas were porous. The 3D images were acquired after reconstruction, including skin, cutaneous tissue, tumor, glandular tissue and blood vessels around the tumor. Every structure of breast in thin sectionss was clear stereo image of breast soild and could be shown satisfactorily. Every shape of stereo image and the structure of breast could be shown by revolving the three dimensional image to different directions, and the tumor's dimensional characteristics were irregular even if it was regular in certain direction. By means of transparent presentation of different structures, the dimensional distance of every structure could be measured. Meanwhile, we could find the blood stream which was rich around the tumor.2. Comparative study between thin sections anatomic 3D reconstruction and 3D CT reconstructionFrom 2004 to 2006, 15 breast cancer patients pathologically diagnosed by preoperative core biopsy were examined with 16 slices helical CT and 3D reconstruction of CT images. 3D reconstruction of the postoperative specimens was also performed with 3D DOCTOR software. The thickness of CT scanning was 1mm, and the data was transmitted to SYNGO workstation to perform 2D and 3D reconstructions of CT images. The specimens were sliced into 0.2mm continuous sections on transversal plane with the computerized miller, and photographed with digital camera. 3DDOCTOR software was used to make three dimensional block diagram.It was found that the characteristics of thin sections anatomy were more plentiful than CT scanning images, and more anatomic structures could be observed. The border between tumor and normal glandular tissue in CT images could be distinguished more clearly. The different shades of tumor interior and blood stream could also be observed in thin sections anatomy, but they could not be seen in CT images. The tumor shapes and infiltrating status observed after 3D reconstruction were basically consistent with CT images. But the tumor margins of thin sections anatomic 3D reconstructions were more accurate. The measurement of the tumor sizes from the two reconstruction methods found the tumor diameter of CT 3-D reconstruction was smaller than that of thin sections anatomic 3-D reconstruction, explaining that CT images could not give a full view of breast cancer. The comparative study of the two reconstruction methods demonstrated shortcomings of imaging, which may facilitate the improvement of imaging for accurate evaluation of tumors.3. The study of tumor infiltrating characteristics with whole breast section techniqueWhole breast section technique was used to study infiltrating characteristics of breast cancer. Ninety-three cases of breast cancer with neoadjuvant chemotherapy and 31 cases without neoadjuvant chemotherapy (the control group) were studied from June, 2004 to August, 2006. All patients acquired preoperative pathological diagnosis. After surgery, all specimens were made into subserial sections to observe the morphological features, tumor infiltrating to skin, cutaneous tissue, big duct of breast and microvessels, and the different infiltrating features between the neoadjuvant chemotherapy specimens and the control group were compared.In the control group, tumor cells distributed intensively, the infiltrating features were very obvious. The infiltrating distance was relevant with tumor size. The greater size of the tumor, the farther the infiltrating distance. After neoadjuvant chemotherapy , the infiltrating features would be weakened, presenting the infiltrating distance was shortened, and necrotic tissue appeared in tumor center. In the neoadjuvant chemotherapy group, infiltrating to skin and subcutaneous tissue was lessened, showing positive cases and infiltrating to nipple-areolar ducts decreased obviously. The observation of HE staining and CD34 immuohistological staining showed infiltrating to microvessels in more positive cases in the control group than in the neoadjuvantt chemotherapy group. Tumor microvessel density (MVD) also declined after neoadjuvant chemotherapy.Conclusion:1. The specimens of breast cancer can keep their basic characteristics after fixation, freezing and slicing, and every structure is clear. It is adapted to 3D reconstruction.2. Thin sections anatomic 3D reconstruction of breast cancer can show irregular features of tumor and structural characteristics around tumor, indicating that tumor growing at every space direction is random. It is fallible to evaluate resection margin according to tumor surface only.3. There are some differences between thin sections anatomic 3D reconstruction and 3D CT reconstruction. Accurate thin sections anatomic 3D reconstruction can help to guide to 3D reconstruction of CT images, and provide theoretical evidence for CT navigation BCT in the future.4. Whole breast sections can observe the full view of breast cancer and the infiltrating characteristics more intuitively. Meanwhile, the infiltrating distance is relevant with tumor size. Surgeon should choose proper excision extent according to different tumor size while using BCT.5. Neoadjuvant chemotherapy can prevent carcinoma from infiltrating to peripheral tissues and increase the chance of BCT and lessen local recurrence rates.6. Digital virtual 3D reconstrustion is feasible in the study of breast cancer. If accurate imagelogy virtual technique is provided with breast cancer, navigation surgery in BCT will be hoped to come true.