| PurposeThe pancreatic cancer has become one of the familiar digestive system malignant tumors currently, and the trend is increasing gradually in the whole world, accounted for about 1—4 percent of the whole body malignant tumors. Because of the deeper anatomic position of the pancreas, complicated function, dormant disease and quick progress, it results in the difficult diagnosis of pancreatic cancer in the early period. The most clinical patients are in the progressive period or later period, so its operational excision rate become low, and the prognosis is very bad. Due to the development of the imaging diagnosis of B ultrasonic, CT, magnetic resonance, ERCP, angiography, etc and the diagnosis of biochemistry and immunology in recent years, diagnostic level of pancreatic cancer has improved adopting the joint application of measurement of tumorous correlative marker and imaging diagnosis. The tumorous cell can excrete many kinds of vascular cell growth factor in the process of tumor growth. VEGF is the most important factor to stimulate hyperplasia of vascular endothelial cell and work a important function in the process of new tumorous angiogenesis. Now the angiogenesis study gradually deepen from the foundation to clinical application, and provide referenced index for tumor diagnosis, pathological period and rating, relapse, metastasis, and prognosis. The quantitative analysis method of tumorous angiogenesis mostly adopts the tumorous microvascular density count, namely applying histological slice through immunohistochemical method count tumorous micro - vessel. Currently the microvascular density count is the quanti-tive standard of angiogenesis in the histological research, but in regard to clinical application, the MVD technique is not still an ideal examination means, because this is a traumatic examination method. The examination accuracy lies on accurate histological material, and cant evaluate the function of tumor angiogenesis activity. Therefore, looking for a kind of examination method of non -wound, speediness, reusable implement in living body and the whole tumorous manifestation, using for the evaluation of tumor angiogenesis and anti - angiogenesis curative effect, forecasting prognosis have the clinical practical significance.The domestic and international scholar have already started to study the application of tumor angiogenesis about MR, tumor contrast degree and manner have good relativity to microvascular density determined by immunohis — to-chemical method on MRI. This shows the possibility that non - wound imaging method gradually replaces immunohistochemical method determined by traumatic ways. Convention CT contrast scan is the main imaging examination method a-bout the diagnosis of pancreatic tumor and the evaluation before operation. With the quick development of CT technique, multisection CT perfusion imaging have already applied to the examination of various diseases and various organs. The e-mergence and application of multisection CT perfusion imaging method are huge progress compared with pute morphologic diagnosis, and accurate evaluation will further to improve about the diagnosis of pancreatic cancer and the surgical operation possibility. This research will apply CT perfusion scan to the normal pancreas , the pancreatic cancer patients and the dog pancreatic cancer model, stud-y the blood dynamics change of pancreatic cancer, and probe into the clinical value of blood perfusion parameters about pancreatic cancer diagnosis and prognostic evaluation, and provide the worthy imaging index for the clinic.Materials and Methods1. case sourceExperiment 1 and 2: collecting from March 2004 to February 2005,50 pancreatic cancer patients and 50 examiner of normal pancreas through midsectionCT scan were used multisection CT'perfusion scan. In 50 pancreatic cancer cases , 32 of male, 18 of female, aging 24 - 85 years old. In 50 normal pancreatic examiners, 27 of male, 23 of female, aging 22 -79 years old. In this research normal pancreatic examiner is divided into 5 groups according to aging (10 cases each group) : first group: less than 30 years old; second group: 31-40 years old; third group: 41 -50 years old; forth group: 51 -60 years old; fifth group: above 60 years old.Experiment 3 ;8 hybrid dogs of China. 24 hours defrosting, recovering, cultivating, and expanding before the surgical operation. The culture liquid contains 10 percent of RPMI1640 of calf serum. The cell are cultured in the 37^ , 5 percent of CO2 culture box. The single layer spreads. 0.25 percent of steapsin digests. Taking the cell in logarithmic growth period starts experiment.Dogs were feeded 3-7 days before the surgical operation, the food were added the bacteriophage before 1 day, dogs were forbidded to eat and drink before 6 hours. Dogs were anaesthetized by injecting to muscle, 5 percent of glucose was injected into outer ankle vein of a side gaskin, Under sterile condition skin was cut below the xiphistemum, exposing the pancreas on the duodenum velamen, about 3 ml of pancreatic cancer cellular liquid ( Pane -1) was injected into the head, body or tail of pancreas using injector, about 1 -2 ml of biologic albumen gum was sprayed to pinprick avoiding the overflowing of cellular liquid and blood, sending back pancreas and closing abdomen. Dogs returned the cage to feed. The bacteriophage was used 3 days after operation, and periodically disinfected using iodine.2. examining condition and methodExperiment 1 and 2: We made conventional CT scan and perfusion scan by GE Iightspeed 16 slice spiral CT. Trainning patient calm breath before scanning. Firstly we made conventional CT scan with 7. 5 - 10mm thickness. After confirming the perfusion section, perfusion scan started with 5mm thickness. A-bout 50ml of non - ion contrast media was injected though median cubital vein by high - press injector at the speed of 4. Oml/sec. The cine scan started after the delay of 5.0sec, and the whole scanning time was about 50sec. The scanning parameters of perfusion are 120kV, 80mA, 512 512 matrix, 26cm DFOV.After perfusion scan, contrast CT scan immediately started with 7. 5 - 10mm thickness, about 40ml of non - ion contrast media was injected though median cubital vein by high - press injector at the speed of 2.5 - 3.5ml/sec.Experiment 3: At 7 -10 days after surgical operation, the dogs were anaesthetized and scanned using conventional CT scan and contrast CT scan with 2. 5mm thickness, The scanning parameters are 120kV, 200mA, 25cm DFOV. A-bout 30ml of non - ion contrast media was injected though outer ankle vein by high -press injector at the speed of 1. 5ml/sec, delay of 10 sec. The contrast media density is that 100ml non - ion is added 30 ml 0.9 percent of Nacl. Observing the disease growth and confirming the focus position, perfusion scanning was performed with 2.5mm thickness. The scanning parameters of perfusion are 120kV, 80mA, 25cm DFOV. About 20ml of non - ion contrast media was injected though outer ankle vein by high - press injector at the speed of 2. Oml/sec, delay of 5 -10 sec, the whole scanning time was about 50sec.2-3 weeks after surgical operation, the anaesthesia was performed under sterile condition. Conventional CT and contrast CT was performed, and further to confirm the focus position, performed perfusion scanning. About 20ml of non - ion contrast media was injected though outer ankle vein by high — press injector at the speed of 2. Oml/sec, delay of 5 -10 sec, the whole scanning time was about 50sec. Pulling out the pipe finally, killing the dogs, and opening the stomach to take out the pancreas.3. immunohistochemical methodAll specimens were fixupped by 10 percent of formalin and wrapped by paraffin , the thickness of continuous slice is 4 jx m. At first, we performed conventional HE dyeing, then made the immunohistochemical dyeing using s - p means.4. imaging diagnosisTwo veteran doctors carry though the CT diagnosis and establish the period of 50 pancreatic cancer cases according to the Hemrickts period way.5. perfusion analysisOriginal data were sended to AW4.1 workstation, Perfusion -3 pancreatic perfusion software bag was used for imaging analysis with the celiac artery as theperfusion artery, ROI <6mm. We choiced many ROI in the different region, ROI between 20 -30mm2(above 50 pixels). In the groups of normal pancreas and pancreatic cancer, the time - density curve(TDC) and other perfusion parameters including BF, BV, MIT, PS are calculated respectively.6. statistical analysisSPSS11.0 statistical software is used to analyze data. The each group number adopts mean standard deviation. We make t test and pearson and spearman correlation between the every parameter of two group samples, and consider it having statistical significance when P <0.05.ResultsExperiment 1: The blood volume of the normal pancreas has a obviously degressive trend going with aging increasing. The perfusion parameter BF, BV of the normal pancreas reduce with aging increasing, they present obviously negative correlation with aging; MTT increases with aging increasing, it present obviously positive correlation with aging; PS has no obvious trend with aging increasing , and has no correlation with aging. Each blood parameter of the normal pancreas has no correlation with gender, among them the average value of parameter BF in male is less than that of in female, average value of B V, MTT, PS in male are higher than that of in female. Each blood parameter of the normal pancreas has also no correlation with weight.Experiment 2: Five patients of 50 cases were confirmed by Pathology and 45 cases had typical imaging change with near organic metastasis and excluded others pancreatic diseases. In 50 pancreatic cancers, the head of pancreatic cancer was 32 cases, the body of pancreatic cancer was 10 cases, the tail of pancreatic cancer was 8 cases. Four period method established according to the Hemricks CT standard;3 cases of 1 period, 16 cases of 2 period, 18 cases of 3 period, 13 cases of 4 period. There is the prominent difference of CT perfusion parameter between the groups of normal pancreas and pancreatic cancer. The blood flow perfusion of pancreatic cancer becomes distinctly less than that of normal pancreas. BF ^BV of pancreatic cancer are obviously lower than normalpancreas , but MTT, PS are higher than normal pancreas. There is prominent statistical significance of BF, BV, MTT and PS between the groups of normal pancreas and pancreatic cancer. The non - ion contrast media density in time -density curve (TDC) of the pancreatic cancer group reduced obviously to compare with time — density curve of the normal pancreas group, the pancreatic cancer organization present obviously low perfusion. BF, BV, and PS of the blood perfusion parameter of the pancreatic cancer obviously increase along with the increment of Hemrick's CT period, they present obviously positive correlation. But MTT descend obviously along with the increment of Hemricks CT period , they present obviously negative correlation.Experiment 3: The blood perfusion parameter PS of 8 dogs pancreatic cancer model present obviously positive correlation with microvascular density, other parameters have no correlation. There are 2 of VEGF negative expression, 4 of weak positive expression and 2 of strong positive expression in 8 cases, the positive expression rate of pancreatic cancer is 75%. BF of the blood parameter in the cases of VEGF positive expression is obviously lower than that of in VEGF negative expression, but PS obviously increased, B V and MTT have no obvious trend. PS presents obviously positive correlation with the VEGF expression, other parameters have no correlation.Conclusion1. The CT perfusion technique provides a kind of non - wound imaging means for evaluating the pancreatic blood and the change of blood dynamics, and makes with quantitative analysis or semi - quantitative analysis to perfusion process. The blood perfusion study of normal pancreas and pancreatic cancer provide the important information for the diagnosis of pancreatic diseases, biological behavior and the curative effect evaluation etc.2. The establishment of the dog pancreatic cancer model provides the experimental foundation for the experimental study of pancreatic cancer, and provids objective basis for the clinical treatment of pancreatic cancer and the prognostic evaluation. |
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