Single-center Retrospective Study On Video-assisted Thoracoscopic Surgery For Locally Advanced Thymic Malignancy

Locally advanced thymic malignancy(LATM)generally refers to thymic tumors of Masaoka stage III and IV,but without distant metastasis.It is a relatively rare and complicated disease.Video-assisted thoracoscopic surgery(VATS)has been used for the surgical treatment of LATM for more than 20 years.But there are still many challenges and controversies in minimally invasive surgery for LATM.The main controversy lies in the safety and the oncological effects of the operation.Recently,with the widespread application of subxiphoid VATS(SX-VATS),it has been clinically proven to be extremely advantageous in the surgical treatment of thymic tumors[4].However,the current reports on the treatment of LATM based on VATS are mainly case reports or series,and there is a lack of clinical case-control or cohort studies,especially prospective randomized controlled studies.In addition,there are still many complicated situations that need to be further understood in clinical practice.For example,how to “strictly” select appropriate cases of LATM to adopt VATS treatment;how do comorbidities such as myasthenia gravis(MG)affect the perioperative outcomes of LATM.This study intends to include LATM cases treated in our center to conduct a retrospective cohort study,so as to compare perioperative indicators and prognosis,and to evaluate the advantages of VATS for LATM.Thus,reasonably determine the indications of LATM for VATS and optimize the perioperative management of those patients.Chapter 1 The application of preoperative symptomatology and CT contour analysis in the preoperative evaluation of LATM Objective: To explore the application value of preoperative symptomatology and CT contour analysis in the preoperative evaluation of LATM.Methods: Retrospectively analyzed the clinical data,preoperative CT and surgical or pathological data of 40 LATM cases who had undergone chest CT examination in our hospital before operation,and compared and analyzed the different symptoms and CT features with surgical/pathological data.Results: The main complaints on entrance included non-MG symptoms,MG symptoms and examination findings.The rates of large vessel invasion of the three groups were 62.5%,23.1%,and 9.1%,respectively,and the difference was statistically significant(P=0.013);There are more large vessel invasions in patients with non-MG symptoms than those in patients with MG symptoms and those found in the examination(non-MG symptoms vs.MG symptoms P=0.034,non-MG symptoms vs.examination found P=0.008),and the examination found had fewer pericardial invasions than non-MG symptoms(P=0.049).There was no statistically significant difference among them as to other invaded organs(P>0.05).The sensitivity,specificity,and accuracy of chest CT scan for lung invasion were 96.9%,62.5%,and 90%,respectively.The sensitivity,specificity,and accuracy of CT for pericardial invasion were 88.5%,57.1%,and 77.5%;the sensitivity,specificity,and accuracy of contrast-enhanced CT scan for large vessel invasion were 92.9%,75%,and 82.4%;the sensitivity,specificity,and accuracy of CT for Phrenic nerve invasion were 75%,62.5% and 65%;the sensitivity,specificity and accuracy of CT for disseminated pleural nodules were 85.7%,100% and 97.5%,respectively.Conclusion: Preoperative symptomatology and CT contour analysis have important value for the assessment of invasiveness and resectability of LATM and help determine the surgical approaches.Chapter 2 The clinical study of SX-VATS for LATM Objectives: 1.To explore the feasibility,safety and oncological effects of SX-VATS in the treatment of LATM,and to summarize relevant surgical experience and skills;2.To analyze the influence of the substernal angle(SA),body mass index(BMI)and surgical experience on the perioperative outcomes of SX-VATS for LATM.Methods: To summarize and analyze the clinical data of 20 LATM cases treated by SA-VATS in our department from June 2016 to January 2021.The main analyzed indicators include: operation time,intraoperative blood loss,surrounding tissues or structures resected with LATM intraoperatively,number of lymph node resected,postoperative hospital stay,postoperative complications and follow-up results.At the same time,according to the size of SA,all patients are divided evenly into two groups,one group with SA<77° and the other with SA>77°,and according to the BMI,all patients are divided evenly into low BMI group(BMI<22.7kg)/m2)and high BMI group(BMI>22.7kg/m2),differences between groups were compared regarding to the operation time,intraoperative blood loss,number of resected lymph node,postoperative hospital stay and postoperative complications.In addition,patients were divided into early group and late group according to the date of operation.The operation time,intraoperative blood loss,number of resected lymph node,postoperative hospital stay and postoperative complications were compared between the two groups to explore the effect of surgical experience on short-term results.Results: All 20 LATM patients completed the operation under SX-VATS.Intraoperative results: the operation time was 120-360 min,with an average of 190±64min,and the intraoperative blood loss was 10-650 m L,with an average of 130±160m L;the surrounding tissue or structures removed during the operation included15 cases of lung wedge resection,10 cases of partial pericardial resection,3 cases of left brachiocephalic vein resection(including 1 case with combined-excision of superior vena cava sidewall),2 cases of left brachiocephalic vein resection,3 cases of left phrenic nerve resection,and 1 case of ascending aortic adventitia.Postoperative results: there were no deaths related to operation,complications occurred in 6 cases,including one case of postoperative myasthenia crisis(POMC)who was discharged after 19 days after MG comprehensive treatment such as plasmapheresis;1 case of POMC with upper gastrointestinal hemorrhage that occurred 2 weeks after the operation,and the patient gave up further treatment and was discharged;1 case with swelling of the left upper limb,left neck,and face,which gradually resolved within 1 week after the operation;3 patients with lung infections was improved after employing anti-biotics;except for the patients who were discharged after POMC,the postoperative hospital stay of the remaining 19 patients was 6-20 days,with an average of 12.1±4.2 days.The postoperative follow-up period was 1-48 months,with an average of 15.7±13.0 months.Two deaths were due to MC or MG-related complications;one recurrence was a recurrence of limited metastases in the lung and pleura,who survived after reoperation.The results of the group study showed that the patients' SA and BMI had no significant influence on the surgical operation and short-term results after surgery.Linear regression analysis showed that in addition to the positive correlation between the patient's BMI and the operation time(r=0.458,P=0.043).There was no correlation between SA and complications,so was the results of BMI.The effect of surgical experience on SX-VATS in the treatment of LATM was manifested as shortened operation time,reduced intraoperative blood loss,and shortened hospital stay,but the difference between the two groups was not statistically significant(P>0.05).Conclusions: 1.SX-VATS of selected LATM is technically feasible and has good short-term results;2.The patient's SA and BMI have no significant effects on the perioperative surgical results,but BMI have a positive correlation with the operation time.Chapter 3 The impact of MG on the perioperative period of VATS for thymic malignancy Objective: To analyze the influence of MG on the perioperative period of VATS treatment in patients with thymic tumors,and to explore the prevention and treatment of perioperative MG-related risks in LATM patients.Methods: Retrospectively analyzed the clinical data of 91 patients with thymic tumors who were treated with VATS in our center from December 2014 to January2021.The patients were divided into three groups according to their preoperative medical history and diagnosis.Group A: without any type of MG(n=35);Group B:patients with mild MG,that is,with ocular myasthenia gravis(Osserman I)or mild general MG(Osserman IIA)patients(n=24);Group C: patients with severe MG,including Osserman IIB,III or IV(n=32).Make comparative analysis of the perioperative indicators of those groups.Also,patients were grouped by complications to analyze the influencing factors of complications.The clinical therapeutic effects of MG 30 days after surgery and the effects of MG on the perioperative period of LATM patients were analyzed,too.Results: The three groups had significant differences in Masaoka staging,WHO pathological classification and postoperative complications,ventilator-supported time,ICU retention time,hospitalization time,and total hospitalization expenses(P<0.05).MG of Osserman IIB or higher types increased the risk of postoperative complications;postoperative indicators such as ventilator-supported time,ICU retention time,hospitalization days and hospitalization expenses of those patients increased significantly(P<0.05).Univariate analysis results suggest surgical clinical staging in onset/ progression,history of preoperative MC,ASA grade III or higher,and Osserman IIB or higher type MG are risk factors for perioperative complications;multivariate analysis shows that Osserman IIB or higher MG is an independent risk factor of postoperative complications.There was no significant difference in the clinical effects of myasthenia gravis between group B and group C at 30 days after operation(P>0.05).A separate analysis of the postoperative indicators of LATM cases found that MG significantly increased the postoperative ventilator support time,ICU treatment days and hospitalization costs of LATM patients,and the difference was statistically significant(P<0.05);but postoperative complications and total postoperative hospitalization days showed no significant difference(P>0.05).Conclusions: 1.MG increases the risk of postoperative complications in patients with thymic tumors;2.Osserman IIB or higher MG is an independent risk factor for postoperative complications of thymic tumors;3.Ventilator support and ICU treatment may help reduce the adverse postoperative effects of MG on LATM patients.Chapter 4 The retrospective cohort study of VATS versus open surgery in the treatment of LATM Objective: 1.To further evaluate the safety and oncological effects of VATS in the treatment of LATM;2.To explore the indications of LATM for VATS treatment.Methods: 45 patients with LATM who were admitted to our hospital and undergoing surgical treatment from June 1,2016 to January 31,2021 were enrolled in this study.The clinical data of all patients were complete and they were followed up until March 1,2021.Patients were divided into VATS group(n=25)and open thymectomy group(OT group,n=20)according to their surgical approaches.The differences in clinical information and outcomes between the two groups were compared.Results: Compared with OT group,the proportion of patients in VATS group who received neoadjuvant chemotherapy before operation was significantly less than that of OT group,and the maximum tumor size on CT was also smaller than that of OT group(P<0.05).Comparison of intraoperative indicators between the two groups showed that the VATS group had shorter operative time and less intraoperative blood loss(P<0.05),and the difference in operative time was statistically significant(P<0.01);VATS was comparable in handling of surgical difficulties caused by infiltration or tight adhesion of pericardium,lung,and phrenic nerve,and the effect in resection of thoracic disseminated nodules is also similar(P>0.05),but VATS is inferior to OT in managing the surgical difficulties related to large blood vessels.VATS was also at a disadvantage when there were more than 3 surgical difficulties(P<0.05).Comparison of postoperative indicators: the difference in postoperative drainage volume between the two groups was not statistically significant(P>0.05).The postoperative complication rate in the VATS group was lower than that in the OT group.The postoperative ventilator support time and ICU stay in the VATS group were shorter than that of OT group;the postoperative hospitalization days and total hospitalization expenses were all less than those in the OT group(P<0.05).There was no statistically significant difference between the two groups in the ratio of lymph node positive/resected cases,WHO classification,resection margin status,Masaoka staging and TNM staging(P>0.05).All patients were followed up for 1-57 months,with an average of 19±16.9 months.During the follow-up,3 cases died and1 case relapsed in the VATS group,4 cases died and 1 case relapsed in the OT group.Upon survival analysis,no statistical significance(Log-Rank test,X2=0.216,P=0.642)was observed between VATS and OT groups.Univariate analysis results:neoadjuvant chemotherapy history,tumor size(>5cm),surgical difficulties in the left innominate vein,surgical difficulties in large vessels other than the left innominate vein,and more than 3(including 3)surgical difficulties are factors that hinder VATS for LATM.Binary logistic regression analysis results show that factors affecting the choice of VATS for LATM include tumor size(OR=2.207,95%CI: 1.152-3.567,P=0.014),Surgical difficulties of large vessels other than the left innominate veins(OR=0.130,95%CI: 0.020-0.860,P=0.034)and intraoperative surgical difficulties?3(OR=8.778,95%CI: 1.105-69.731,P=0.040).Conclusions: 1.For the strictly selected LATM cases,the postoperative effect of VATS is significantly better than that of traditional thoracotomy or sternotomy,and the long-term oncological effect is comparable.2.VATS for LATM requires strict indications.LATM patients who meet the following conditions may choose VATS:(1)the maximum tumor size on CT ? 5cm,(2)No surgical difficulties caused by large blood vessels(the left innominate vein excluded),(3)surgical difficulties <3,(4)Patients without a history of neoadjuvant chemotherapy.