| Part Ⅰ: the Potential Correlations between Serum Tumor Markers and Clinicopathological Characteristics of Thymic Malignancies Object to explore the potential correlations between serum tumor markers and clinicopathological characteristics of thymic malignancies.Methods A retrospective research was carried out about 159 patients with thymic malignancies who underwent surgical resection with a define postoperative pathology from November 2012 to September 2016,in Department of Thoracic Surgery,Shanghai Chest Hospital,Shanghai Jiaotong University.The clinical data included age and gender.Laboratory data included five serum tumor markers namely CEA,Cyfra 21-1,SCC,NSE and CA 125.Pathological data included histological type,TNM stage and the longest diameter of tumor.The differences of five serum tumor markers in different tumor stages and histological types were analyzed and compared,and the possible reasons for these differences were discussed.Results there were 159 cases of thymic malignancies.In patients older than 53 years old there was a high level of serum CEA(P=0.040);the serum CEA level in male group was higher too(P=0.015),but the serum level of CA 125 was lower(P=0.045);non R0 resection group showed higher levels of serum Cyfra 21-1 and NSE(P=0.028,P=0.033);the serum concentrations of Cyfra 21-1 and NSE of T4 group were significantly higher(P=0.000,P=0.004);patients with lymph node invovled(N1-2)presented a higher level of serum NSE(P=0.009);patients with thymic carcinoma were associated with higher levels of serum Cyfra 21-1 and NSE(P=0.000,P=0.010).The tumor size and pleural dissemination were not significantly correlated to the five tumor markers;ROC curve was analyzed about Cyfra 21-1 in T stage: AUC=0.837±0.076,P=0.001.when the cut-off value was defined as 1.86ng/ml,the sensitivity was0.875 and the specificity was 0.748;Cyfra 21-1 in the histological types: AUC=0.734±0.057,P=0.000,when the cut-off value was defined as 1.75ng/ml,the sensitivitywas 0.667 and specificity was 0.735;NSE in N stage: AUC=0.785±0.061,P=0.007,when the cut-off value was defined as 12.4ng/ml,the sensitivity was 0.875 and the specificity was 0.656.Conclusion the positive rate of serum tumor markers in thymic malignancies was quite low,thus the normal value of Cyfra 21-1 and NSE for thymic malignancies may need to be redefined.The increase of serum Cyfra 21-1 may suggest that the T stage was relatively late and the tumor was more malignant.The cut-off value of Cyfra 21-1to predict T4 and thymic carcinoma may be 1.86ng/ml and 1.75ng/ml.The increase of serum NSE may indicate the occurrence of neuroendocrine tumor.Part Ⅱ: Predictive value of serum tumor markers about postoperative recurrence of thymic malignancies Object to investigate the possible role of serum tumor markers in predicting postoperative recurrence of thymic malignancies Methods A retrospective research was carried out about 102 patients with thymic malignancies who underwent surgical resection with a define postoperative pathology from November 2012 to September 2016,in Department of Thoracic Surgery,Shanghai Chest Hospital,Shanghai Jiaotong University.The clinical data included age and gender.Laboratory data included five serum tumor markers namely CEA,Cyfra 21-1,SCC,NSE and CA 125.Pathological data included histological type,TNM stage and the longest diameter of tumor.Follow-up data included follow-up concentrations of serum tumor markers,follow-up chest CT.The study summarizes the possible role of serum tumor markers in predicting postoperative recurrence of thymic malignancies.Results The median follow-up of the 102 patients was 28.3 months.9 patients presented recurrence or metastasis,including 1 cases of lymph node metastasis,3cases of pleura recurrence or dissemination and 5 cases of distant metastasis.ROC curve was carried out about the preoperative serum Cyfra 21-1 about recurrence and metastasis,AUC=0.778±0.078,P<0.05.When the cut-off value was defined as 1.66 ng/ml,the sensitivity was 0.889 and the specificity was 0.677.The levels of serum Cyfra 21-1,SCC and CA 125 in the patients with recurrence or metastasis were significantly higher(P=0.000,P=0.000,P=0.005,respectively).When the cut-off value of Cyfra 21-1 was defined as 2.66ng/ml,the sensitivity was 0.667 and the specificity was 0.92.When the cut-off value of SCC was defined as 1.5ng/ml,the sensitivity was 0.667 and the specificity was 0.839.When the cut-off value of CA 125 was defined as 13.93ng/ml,the sensitivity was 0.778 and the specificity was 0.710.Conclusion histotype and radical resection were prognostic independent risk factors.The preoperative serum Cyfra 21-1 could predict postoperative recurrence or metastasis to some extent,and the cut-off value was 1.66ng/ml.The level of serum Cyfra 21-1 may provide a certain help for clinicians when there was a suspicious lesions which was difficult to identify whether it was a relapse or not,and the cut-off value was 2.66ng/ml.The diagnostic effectiveness of serum SCC and NSE was not so good as Cyfra 21-1 for the diagnosis of recurrence and metastasis,and the cut-off value were 1.5ng/ml and 13.93ng/ml,respectively.Part Ⅲ: The relationship between serum tumor markers and the therapeutic effect of induction therapy in thymic malignancies Objective to evaluate the possible role of serum tumor markers in performing the induction therapy in patients with thymic malignancies Methods A retrospective research was carried out about 159 patients with thymic malignancies received direct surgical resections and 33 patients received surgical resections after induction therapy,from November 2012 to September 2016,in Department of Thoracic Surgery,Shanghai Chest Hospital,Shanghai Jiaotong University.The clinical data included age and gender;laboratory data included serum tumor markers namely CEA,SCC,NSE,Cyfra 21-1 and CA 125,both before and after the induction therapy;imaging data included the tumor sizes on chest CT both before and after the induction therapy,and the existence of pleural effusion.The pathological data included histotype and TNM stage.To study the changes of serum tumor markers before and after induction therapy,and to compare and analyze the differences between operation group and induction group,and to summarize its possible importance for induction therapy.Results the total remission rate of induction therapy was 69.7%.In responding group(n=23),serum Cyfra 21-1 and CA 125 decreased significantly(P=0.046,P=0.049).The two markers showed a slight decrease in no-responding group(P=0.545,P=0.257).Before the induction treatment,serum CA 125 level was significantly higher in pleural effusion group(n=8)than that in no pleural effusion group(n=25)(P=0.049),after induction therapy,pleural effusion was completely absorbed in all the 8 patients,and compared to no pleural effusion group,the serum level of CA 125 was similar(P=0.529).Compared to operation group,serum levels of Cyfra 21-1,NSE and CA125 were significantly higher in induction group.a significantly higher level(P=0.000,P=0.001,P=0.000,respectively).At the same time,there were significant differences anbout tumor stage,tumor size,histotype and resection rate between the two group(P=0.000)Conclusion in addition to the diminishing of tumor volume in imaging,the tumor markers(Cyfra 21-1 and CA 125)also decreaseed in hematology.The increase of serum CA 125 may be associated with pleural effusion.With the support of imaging,the increase concentrations of serum tumor markers(especially Cyfra 21-1 and NSE)indicated that an advanced tumor stage,a more malignant histotype or the possibility of incomplete resection.Induction therapy can be considered in order to achieve better prognosis.Part Ⅳ: The value of concurrent introthoracic hyperthermic chemoperfusion in patients with pleural dissemination of thymic malignancies Objective to explore the value of the combination of lung-sparing pleurectomy with introthoracic hyperthermic chemoperfusion in patients with pleural dissemination of thymic malignancies Methods 37 patients were enroll to a prospective study who underwent thymectomy and pleurectomy combined with introthoracic hyperthermic chemoperfusion,from December 2015 to May 2017 in Department of Thoracic Surgery,Shanghai Chest Hospital,Shanghai Jiaotong University.Proper surgical approaches and methods were chosen according to the extent of tumor.After the resection of primary lesions and pleural lesions,the perfusate at a temperature of 40 degrees containing cisplatin(100mg/m2),was filled in the affected thoracic cavity.Record the preoperative clinical data of patients,as well as the intraoperative vital signs,including heart rate,temperature,mean blood pressure,central venous pressure and blood oxygen saturation.Observe the ocurrence of postoperative adverse reactions,including nausea and vomiting,dysfunction of liver and kidney,arrhythmia,bone marrow suppression and so on.The patients were followed up and it would be recorded if there was a sign of recurrence in chest CT during the following up.Results 36 patients successfully completed the introthoracic hyperthermic chemoperfusion,while 1 case failured.The vital signs were stable during the progress,after the perfusion,only the heart rate and temperature showed statistically significant differences(P=0.016,P=0.000).All 37 patients recovered well after operation,without serious complications or hospitalized death.Only 2 cases had nausea and vomiting within three days after the operation.36 patients who successfully completed the introthoracic hyperthermic chemoperfusion had no dysfunctin of liver and kidney on the first day after operation.The WBC count increased significantly and platelets decreased significantly(P=0.000,P=0.006).31 patients followed up at6 th month after operation.1 case with cervical lymph node metastasis,1 cases with pulmonary metastases,1 case with local oligomeric recurrence.6 cases lost in follow up,2 of them died from non tumor reasons one month and three month after the operation,respectively.The serum tumor markers in 31 patients when followed up were analyzed and compared to those before operation.The CA 125 level decreased significantly at 6th month after operation(P=0.022),while Cyfra 21-1 level sightly decreased(P=0.055).Conclusion for patients with pleural disemination,the combination of lung-sparing pleurectomy with introthoracic hyperthermic chemoperfusion could significantly lower the perioperative risk and ensure the perioperative safety.During the operative progress,it’s important for surgeons,anesthetists and nurses to cooperate with each other to monitor vital signs closely.Once there is a sign of ocurrence of serious complications,it is necessary to timely terminate the perfusion progess,if necessary.This new treatment model can effectively reduce the short-term local recurrence,and the long-term effect remains to be further analyzed after a longer follow up period.In addition,the elevated level of serum CA 125 may be associated with pleural involvement,which may suggest a potential pleural metastasis. |
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