The Roles Of Multimodality Imaging And Cytokines In The Diagnosis And Prognosis Of Ovarian Cancer

Part I The value of PET/CT,enhanced CT,conventional MRI,and DWI in differential diagnosis of ovarian tumors and ovarian fallopian tube ovarian abscessObjective: To explore the differential diagnostic ability of positron emission tomography(PET/CT),conventional magnetic resonance imaging(MRI)and diffusion-weighted imaging(DWI)for ovarian fallopian tube tumors and ovarian fallopian tube abscess(TOA).Materials and Methods: A retrospective analysis of patients who were suspected of being malignancy in the accessory area after a sonographic examination in our hospital between January 2008 and May 2015 was not available.All patients underwent follow-up enhanced CT,conventional MRI,and DWI and 18F-FDG PET/CT examination.Finally,a clear pathological diagnosis was obtained after laparoscopic or laparotomy.Two radiologists evaluated enhanced CT,conventional MRI,and conventional MRI combined with DWI sequences,while two nuclear medicine physicians evaluated PET/CT images.The diagnostic results were then quantified using a two-class assignment method: 1 = tumor group,0 = TOA group.The receiver operating characteristic curve(ROC)was used to compare the patient’s enhanced CT,PET/CT,conventional MRI,and MRI with the DWI sequence.The sensitivity,specificity,and positive predictive value(PPV),negative predictive value(NPV)were calculated and statistical analysis was performed using Chi-square test and Log-Rank test.Results: The sensitivity of 18F-FDG PET/CT,enhanced CT,conventional MRI,and DWI-MRI were 86.7%,78.6%,87.5%,and 95%,respectively;the positive predictive values were 68.4%,57.9%,73.7%,and 100%,respectively.The accuracy rates were81.4%,74.4%,83.7%,and 97.7%,respectively.The accuracy and sensitivity of DWIMRI in the differential diagnosis of tubal and ovarian fallopian tube abscesses were significantly higher than those of the other three methods.Conclusion: DWI combined with conventional MRI has high clinical value in the differential diagnosis of ovarian tumor and ovarian fallopian tube abscess.Part Ⅱ Prognostic Risk Factors Analysis of Ovarian CancerObjectives: To analyze the clinical and imaging risk factors of primary ovarian cancer patients in our hospital and provide theoretical basis for patient treatment and prognosis evaluation.Materials and Methods: A total of 210 patients diagnosed with Ovarian Cancer admitted to Shanghai Xinhua Hospital and its Chongming Branch from January 2010 to December 2016 were retrospectively analyzed.Among them,the patient’s age,menstrual status,postmenopausal vaginal bleeding,and activity were collected.Number of births,fever,tumor side,abdominal pain,abdominal distension,changes in bowel habits,clinical stage,surgical methods,the number of preoperative chemotherapy,postoperative chemotherapy,reproductive history,menarche age and tumor size,number of lesions,pelvic cavity Clinical data such as fluid transfer sites and lesion size,mean ADC value of the solid part of the lesion,maximal enhancement fraction and maximum enhancement slope(MSI)and signal enhancement rate(SER)without significant enhancement,presence or absence of tumor residuals,and residual tumor size,maximum standard uptake(SUVmax),tumor metabolizing volume(MTV),tumor glycolysis total(TLG)image data.The patients with stage I-II and stage Ⅲ-Ⅳ were compared and analyzed by t-test and chisquare test to find out statistically significant indicators,and then these indicators were used to analyze the survival of all patients with ovarian cancer.In order to exclude these indicators from interfering with each other,we used the multivariate Cox proportional hazards regression model to analyze prognostic factors with statistically significant differences in stage I-II and stage Ⅲ-Ⅳ as survival variables.Results: The number of live births in stage Ⅲ-Ⅳ patients was higher than those in stage I-II patients,but the difference was not statistically significant;statistically significant clinical indicators in patients with stage I-II and stage Ⅲ-Ⅳ included changes in urine habits and menopause.Postoperative vaginal bleeding and frequency of preoperative chemotherapy,surgical methods;imaging parameters include preoperative tumor metabolic volume(Metabolic tumour volume(MTV)total preoperative glycolysis(Total lesion glycolysis,TLG),preoperative maximum enhancement slope(MSI).Quantitative indexes obtained critical values ??by ROC curve.Kaplan-Meier survival analysis showed MTV> 90.2cm3,TLG> 921.3g,postoperative tumor residuals,preoperative hyper-enhancing zone maximum enhancement slope(MSIh)<0.949,preoperative low-intensity The maximum enhancement slope(MSIh)was less than 0.621,suggesting a poor prognosis.Logrank test P=0.000.The differences in ADC values ??and SUVmax between stage Ⅲ and stage Ⅲ-Ⅳ patients were not statistically significant,and no further survival analysis was performed in this study.Conclusion: Preoperative PET/CT parameters preoperative MTV>90.2cm3,preoperative TLG>921.3g,postoperative residual tumors,preoperative hyperenhancing zone maximal enhancement slope(MSIh)<0.949,preoperative low enhancement zone maximum intensive slope(MSIh)< 0.621,patient response should be closely monitored.Preoperative solid lesions of some ADC values,SUVmax levels have no prognostic value.The number of live births in patients with stage Ⅲ-Ⅳ in this group was higher than those in stage I-II but not statistically significant.Part Ⅲ Magnetic Resonance Imaging of Ovarian Carcinoma Detected by Superparamagnetic Nano Iron Oxide(USPIO)-labeled MacrophagesObjective:To evaluate the effect of phagocytosis of USPIO-infiltrated macrophages on tumor sites in ovarian cancer.Using M-CSF and GM-CSF to increase mononuclear macrophage mobilization and infiltration from the bone marrow to subcutaneous xenografts of ovarian cancer in nude mice,and to study the enhancement of contrast enhancement.In order to evaluate the safety of these cytokines,we further investigated the effect of M-CSF,GM-CSF,and G-CSF on the proliferation of serous cystadenocarcinoma SKOV-3 cells,and explored its mechanism.Materials and Methods: The effects of different concentrations of poly-L-lysine coated and uncoated USPIO on the toxicity and phagocytic efficiency of mouse macrophage RAW246.7 cells were explored,and then different concentrations of MCSF and Effect of GM-CSF on phagocytosis of macrophages.The effects of M-CSF,GM-CSF,and G-CSF on the proliferation and migration of SKOV-3 cells were investigated by scratch experiments.The effect of these cytokines on the proliferation of SKOV-3 cells was investigated by CCK8 assay.Western Blot was used to detect the effect of these cytokines.The expression level of three cytokines in SKOV-3 cells and the expression levels of signal molecules ERK,P-ERK,P38,and JNK downstream of the MAPK signaling pathway were preliminary investigated for the mechanism of promoting proliferation.Finally,the signal changes of the RAW264.7cells induced by M-CSF and GM-CSF and the SKOV-3 skin xenografts in nude mice were observed and measured under the T2 MAP sequence.Results: When the concentration of iron in the cell culture medium was 25-50 ug/ml,the iron phagocytosis rate of the macrophages could satisfy the requirement of imaging.The animal experiment was conducted according to the iron concentration of50 ug/g body weight to meet the requirement of the imaging.Poly-L-Lysine coated USPIO has little effect on the phagocytosis of macrophages.Instead,it will increase the toxicity of the contrast agent to the cells and cause macrophage necrosis.All three cytokines had the effect of promoting the proliferation of SKOV-3 cells,but G-CSF had the strongest effect,M-CSF was the second,and GM-CSF was the weakest.There was a statistical difference between the G-CSF group and the control group.CCK8 showed significant difference in absorbance on days 2,3,and 4 in the G-CSF group and the control group.Western Blot experiments confirmed that several signaling molecules ERK,P-ERK,P38 and JNK downstream of MAPK were in different degrees of activation.Compared with the control group,M-CSF and GMCSF can shorten the T2 time of subcutaneously transplanted USPIO tumor in nude mice.Conclusion: At the cellular level,the USPIO macrophage carries a good imaging effect.All of the three cytokines promoted the proliferation of SKOV-3 cells,with GCSF being the strongest,followed by M-CSF and GM-CSF.There was a statistical difference between the G-CSF group and the control group.At the animal level,MCSF and GM-CSF enhance macrophage imaging.