| BackgroundHigh intensity focused ultrasound(HIFU) ablation is a non-invasive technology for the treatment of solid tumors. It focuses ultrasound energy in the body, forming biological focal region of mm diameter class of biology. Using instant high temperature effect, cavitation effect and mechanical effect to make the target tissue instantaneous temperature of 65 ~ 100 ℃, thus reach solidification protein and kill cells to destroy the tumor tissue. It has been widely used in clinical treatment of various solid tumor, especially for the pancreatic cancer patients who can’t accept surgery. After HIFU ablation on the pancreatic cancer, the quality of life of patients significantly improved, patients’ pain alleviated and patient survival effectively prolonged.Although some preliminary clinical application proves that the effect of HIFU treatment of pancreatic cancer is clear, but pancreas is an important organ which has the function of the internal and external secretion, its physiological function and pathological changes is closely related to life. The study shows that if islet structure is damaged, islets number will be significantly reduced, the endocrine capacity will reduce. Whether can cause damage the structure of the target, especially for the islet structure damage and affect the pancreatic endocrine function on the basis of HIFU in the effective treatment of pancreatic cancer,was lacking the basic theory research. But the islet cell has certain potential of repair and regeneration ability, there are a few of alpha cells can transform into beta cells. So HIFU on the basis of the effective treatment of pancreatic cancer, can cause damage to the structure of the target, especially for the islet structure damage, the structure and function of the pancreas will have long-term effects after the injury, lack of the basic theory research.This topic established animal model of rat pancreatic cancer, then analyzed long-term pancreatic cancer(islets) structure and the change of the secretion after HIFU ablation on rat pancreatic cancer, and explore the pancreatic islet structure and function of the outcome after HIFU ablation on rats situ pancreatic cancer. Objective1.To analyze the body of malignant pancreatic cancer characterization of change after HIFU ablation on rat pancreatic cancer, CA199 as malignant pancreatic cancer markers.2. To analysis of HIFU ablation after rat situ pancreatic cancer, pancreatic histological changes of the structure, the research on the rules of islet structure outcome in the period of 3 months.3. To analysis of HIFU ablation rat situ pancreatic cancer, the change of islet secretion, studying the outcome of pancreatic endocrine function in the period of 3 months. Methods1. Using dimethyl benzene and anthracene(7, 12- dimethylbenz anthracene(a), DMBA) embedding method to induce rat model of pancreatic cancer in situ, conventional pathology biopsy H.E staining, and observed the pancreatic tissue pathological changes, then used Mrcro- 7.0 T MR imaging to diagnosis and filtrate pancreatic cancer model in rats.2. The 30 pancreatic cancer SD rats were randomly divided into the HIFU ablation group and control group, and 15 healthy pancreatic cancer SD rats as the normal group. Using the frequency of 10.2 MHz, focal length in 1-5 mm, pulse 1000 hz, frequency of 5w focused ultrasound to ablate the rat pancreatic cancer, then observed rat pancreas tumor imaging changes in the period of 3 months. Selected 3 rats from each group randomly respectively immediately after ablation, on the four days, 1 week, 1 month and 3 months, using ELISA method to detect the rat serum insulin, glucagon, CA199 levels; 4% paraformaldehyde fixed pancreatic tissue of rats, paraffin embedding, conventional biopsy, H.E staining to observe rat pancreatic tissue characteristics, two-step immunohistochemical methods detected insulin, glucagon antigen and CA199 expression. Results1. Pancreatic cancer in situ embedding DMBA in rats after 12 months, 7.0 T MRI scanning showed little animals pancreatic tumors generally located in the upper left kidney, assumes the circular or elliptic, 5-- 10 mm diameter range. DMBA induced rat tumor rate was 75%(30/40).2. By H.E staining, the experimental group rats pancreatic tissue was infiltrated a large number of inflammatory cells under light microscope after HIFU ablation 4 days and 1 week. Imaging showed the biggest diameter than the experiment group narrowed after HIFU ablation 1 month. H.E Pathological histology showed coagulation necrosis area was absorbing gradually, and the absorbed part was net-like structure. Imaging showed tumor diameter narrowed on the 3 months after ablation, Histology showed coagulation necrosis area was by a large number of absorbed. CA199 immunohistochemical results showed that in normal pancreatic tissue of rats, CA199 negative antigen expression, the pancreatic cancer control in rat pancreatic tissue CA199 positive expression. Experimental group immediately after HIFU ablation to 3 months, The CA199 expression was negative in the rat pancreas ablation target groups; CA199 serological results showed that the immediate to 3 months after HIFU ablation, the experimental group rats serum CA199 level 17.42 ng/ml, 16.21 ng/ml, 15.43 ng/ml, 14.58 ng/ml, 14.52 ng/ml was significantly lower than the control group 21.57 ng/ml, 22.04 ng/ml, 21.56 ng/ml, 22.03 ng/ml, 21.68 ng/ml(P < 0.05), and the control group rats serum CA199 level was significantly higher than that of normal group 13.98 ng/ml, 13.99 ng/ml, 14.97 ng/ml, 14.99 ng/ml, 15.01 ng/ml(P < 0.05).3. The normal control group islet’ was morphology rule, structural integrity, islet was colored light shallow cells, pancreatic islets were larger, approximate circular or oval shape, uniform distribution of islet cells, cell boundaries clear. Beta cells secreteed insulin particles is rich, color brown, neat, widely distributed. Alpha cells secreted glucagon was less coloring, but distributed evenly around the islets; Islet morphology is irregular in the pancreatic cancer control, Sparse islet size was differ, the number deduced, distribution, and irregular strip break. Gland bubble boundary ambiguity, and cavitation area. Insulin particles of beta cells secreted was less, shading, loosely arranged islet cells. Glucagon particles of a cells secreted was less, uneven distribution, a section of the belt, ablation zone islet morphology was completely destroyed immediately after HIFU ablation, not seen a, beta cell secretion of glucagon and insulin, but in the melt border a, beta cells secretory granules was less, the experimental group of insulin and glucagon expression level was significantly lower than control group and normal group(P < 0.05); 1 week after HIFU ablation, still did not see islet structure in ablation area, melting in border a, beta cells secretory granules was less; 1 months after HIFU ablation, melting in border, visible islet cell morphology, but the form was incomplete. a, beta cell secretion of glucagon and insulin particles increased, but not complete islet structure; FUS ablation after 3 months, the ablation border, islet cell density increased, the cell boundaries clear, compared with normal group, islet morphology more rules, cell distribution was uniform. Beta cells secrete insulin particles was more, color was deeper, structure compared with normal group tend to be more complete. Experimental group insulin expression level was significantly higher than that of control group(P < 0.05). But a still less, glucagon secretion granules had no significant difference between the normal group(P >.05).Insulin and glucagon serological results showed that immediately after HIFU ablation, the experimental group rats pancreatic tissue insulin levels m IU / 47.11 L is significantly higher than control group in 33.68 to 37.29 m IU m IU/L and the normal group/L(P < 0.05);Control group rats pancreatic tissue insulin level was significantly lower than normal group(P < 0.05). In the control group rats pancreatic tissue insulin levels significantly below normal group 33.29 m IU m IU / 31.29 L/L(P < 0.05).1 month 4 days after HIFU ablation, 3 months after HIFU ablation experimental rat pancreatic tissue insulin levels m IU / 31.86 L, 33.29 m IU m IU/L were significantly higher than control group in 27.81 / L, 28.74 m IU/L(P < 0.05); Control group rats pancreatic tissue insulin levels m IU / 27.81 L, 28.74 to 32.03 m IU m IU/L was significantly lower than normal group/L, 32.53 m IU/L(P < 0.05).And serum glucagon level immediately after ablation and only four days after ablation, the experimental group level 259.52 pg/ml, 277.21 pg/ml is significantly higher than control group in 244.91 pg/ml, 259.24 pg/ml(P < 0.05). Conclusions1. Pancreatic necrosis area gradually narrowed and the expression of CA199 levels and serum CA199 levels significantly reduced in the period of 3 month after HIFU ablation rat pancreatic cancer, these results shows that HIFU ablation can reduce the malignant degree of pancreatic cancer.2. FUS ablation rats’ pancreatic cancer caused pancreatic tumor tissue coagulation necrosis and at the same time target damaged islets structural, affected the endocrine function of a,β cells. Rat islet morphology structure was gradually integrated, the serum insulin and glucagon levels tended to be normal in the period of 3 months, these results showed that islet structure and endocrine function outcome was good. |
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