| Objective: This study applied a digital three dimensional reconstruction technique(D3DR) to surgical diagnosis and treatment of hepatic alveolar echinococcosis(HAE). We wished to evaluate the application value of D3 DR in preoperative assessment and surgical planning for liver resection and autotransplantation of HAE, and provide a more accurate individualized method for surgical planning; We established a large animal model of HAE to verify the precision of D3 DR, explored to lay the foundation and provide new idea for the clinical and experimental research of HAE in the future. Methods: Part one: 1.106 consecutive patients with HAE underwent hepatectomy in our hospital between May 2011 and January 2015 were divided into D3 DR assessment group(group A) and the traditional imaging assessment group(group B).Through analyzed the clinical data, we summarized the disease characteristics of HAE; 2.59 patients underwent preoperative 3D reconstructions and virtual 3D liver resection before surgery(group A). Another 47 patients used conventional imaging methods for preoperative assessment(group B). The whole liver volume, lesion volume, and the important parameters such as vascular diameter were measured by different methods; 3.Made surgical planning and optimized the operation scheme in the two groups based on D3 DR and traditional CT data, respectively, and performed the operations; 4.Outcomes of hepatectomy and follow-up results between the two groups were compared. Part two: 1.The clinical data of 27 end-staged hepatic echinococcosis patients underwent autotransplantation or living donor liver transplantation from May 2011 to August 2015 were retrospectively analyzed; 2.The anatomical structure of livers were analyzed by D3 DR software(IQQA-3D Liver), and made precise assessment of the vascular invasion, measured the normal liver volume. A variety of surgical planning made by D3 DR software after virtual surgery based on the software. The multi professional discussion made the final liver transplantation procedures;3.According to the preoperative design, we completed the clinical transplantation surgery, and observed the perioperative and postoperative follow-up results for all of the patients. Part three: 1.12 experimental mini-pigs were divided into the dexamethasone group with infection, cyclosporine group with infection, drug control group without infection, and blank control group according to whether use immunosuppressant and infection. Multipoint inoculated with homogenate medium of E.mutilocularis by percutaneous liver puncture under ultrasound guidance; 2.Multiple imaging methods and D3 DR applied to the dynamic follow-up for the growth of lesions. At the end of the experiment, the status of lesions were compared between every groups, and pathological examination and product of the Cob gene semi-quantitative PCR detection gene sequencing were used to diagnosis the lesions; 3.The concentration change trend of Th2 and Th17 related cytokines(IL-2, IL-4, IL-10, TGF-beta, IL-17 A, IL-17 F, IL-22, IL-23, IFN-γ) in the peripheral blood were compared during the follow-up period. And the IL-4, IL-17 A, IFN-γ, Foxp3 gene expression change trend in different groups were compared in the peripheral blood and liver lesion tissues too. Results: Part one: 1.3D reconstruction of the liver clearly illustrated the positional relationship between the liver, lesions, and hepatic blood vessels in group A, and at least two different resection planning were designed based on D3 DR in group A, the surgical planning were determined based on the surgeon’s experience in group B; 2.Surgical procedures of all 59 patients in group A were consistent with their preoperative 3D reconstruction virtual surgery. Among the 47 cases in group B, the surgical procedures of 4 patients were changed due to inconsistency between exploration results and preoperative imaging evaluations.Estimated resection liver volumes in both groups had good correlation with actual graft weight(r-group A=0.978; r-group B=0.960); 3.There was no significant difference in preoperative data between the two groups. Compared with patients in group B, those in group A had a significantly faster operation time(227.1±51.4 minutes vs 304.6±88.1 minutes; P<0.05), less intraoperative blood loss(308.1±135.4 m L vs 458.1±175.4 m L; P<0.05) and lower requirement for intraoperative blood transfusion(186.4±169.6 m L vs 289.4±199.2 m L; P<0.05).There was a significant dominance in group A for serum level of albumin(26.3±5.9 g/L vs 22.6±4.3 g/L; P<0.05). Other postoperative laboratory parameters(serum levels of aminotransferase and bilirubin; prothrombin time) and duration of postoperative hospital stay were similar. Disease incidence of postoperative complications and the recurrence rate in group B is significantly higher than in group A, patients with postoperative 3 to 46 months follow-up(mean 17.3 months). Part two: 1.26 HAE patients underwent liver resections and liverautotransplantation and another 1 patient have living liver transplantation and the using surgical strategies consistent with pre-operative surgical planning in 3D reconstruction; 2.There was no significant difference between whole liver volume(2588.06±740.73cm3 vs 2783.46±786.63cm3, t=-6.116, P > 0.05) and lesion volume(1165.48±657.47cm3 vs 1255.07±685.78cm3, t=-3.338, P> 0.05) measured by 3D and traditional 2D manual tracing from CT; 3. The Intraoperative real situation was consistent with the preoperative planning. The remaining liver volumes(including the living donor liver transplantation for liver volume) calculated by 3D and 2D CT were 873.33±257.89cm3 and 978.74±303.34cm3(t=-3.118, P>0.05). Part three: 1.All of 9 experimental mini-pigs in research group(group A、B and C) were observed infection in different levels, but in group D, the maximum diameter of lesions is 6cm, and minimum is 2mm, the infection rate was 88.9%. Pathological examination and gene sequencing confirmed the diagnosis of HAE; 2. Follow-up results of the imaging examinations(US、CEUS、CT、MRI、PET-CT、D3DR) conformed to the characteristic of HAE, and were consistent with laparotomy results. The average volume of liver and spleen by water displacement method were 403.33±50.69cm3, 99.58±35.89cm3, there was no significant difference compared with the preoperative results based on D3 DR method(t-liver=0.435 P>0.05 t-spleen=0.271 P>0.05); 3.The levels of CREA and BUN in group were significantly increased in group B during the early drug and infection stage(0~6w), but showed a trend of gradual decline during the middle stage of dose(14~20w), in the late infection stage(28~32w), down to normal levels, other laboratory examination indexes in no marked differences trends between the experimental group and control group; 4. Compared with group D, the concentration of Th2 related cytokines(IFN-γ, IL-2, IL-4, IL-10, TGF-beta) in the peripheral blood showed different levels of increased trends in early infection stage, and decreased in the late stage. Th17 related cytokines(IL-17 A, IL-17 F, IL-22, IL-23) showed continuous declination during all follow-up period. And the IL-4, IFN-γ, Foxp3 gene expression change trend in infection group were increased than blank control group, but IL-17 A showed decreased in the peripheral blood. In the liver lesion tissues, the gene expression of IL-4, IFN-γ, Foxp3 higher than the other three groups, but IL-17 A was lower. In the liver tissue close to the lesions, IL-4, IL-17 A, IFN-γ, Foxp3 expressions were lower than the lesion group, IL-4, IFN-γ, Foxp3 were higher than control group and far from lesion group, but IL-17 A has a lower expression. In the liver tissues far from the lesions, IL-4, IFN-γ, Foxp3 showed higher expression, but IL-17 A lower expression. Conclusions: 1.Compared with the traditional CT image assessment methods, application of D3DRshowed more precise in anatomy assessment and surgical planning for the liver surgery, and surgeon was more convenient and quick operation, the evaluation result is reliable, and can better grasp the indications of autologous transplantation; 2.D3 DR can shorten the operative time, reduce intraoperative blood loss and blood transfusion volume, so as to reduce the surgical risk and incidence of complications, improve the radical resection of HAE lesions; 3.HAE mini-pig secondary infection animal model were established successfully, and initial discovered immune inhibitors may have a role in promoting growth of HAE, its mechanism needs further experimental studies prove that; We preliminary grasped the mini-pig basic examination scope in variety of imaging examination. The compared results of volume measured between water displacement and D3 DR methods showed that D3 DR measurement has high accuracy and low error rate. Through the concentration of Th2 and Th17 related cytokines peripheral blood, gene expressions level in peripheral blood and tissue, the results are basically in agreement with always HAE clinical and animal experiments, the immunosuppressant drugs may be the reason of some consideration and different tendency. |
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