Although the occurrence is low, thymic tumors are one of the most frequent mediastinal neoplasms, and account for 5% of all thymic malignancies . Venuta et al. have reported that approximately 30% of patients with thymic malignancies are asymptomatic, 40% of them show local symptoms, and only 30% exhibit systemic symptoms . Thus, except for those displaying systemic symptoms such as myasthenia or pure red cell aplasia, many thymic malignancy patients lack clinical manifestations. Therefore, a large number of thymic carcinoma is of relatively late stage at the time of diagnosis. In this study, 17 patients were asymptomatic or had mild clinical symptoms such as chest-back pain and chest tightness, accounting for 65.39% of all patients. Besides, for adhesion to great vessels like SVC and characteristics of aggressive growth of malignant tumors, thymic carcinoma are very difficult to completely remove which leads to a poor prognosis. We retrospectively analysis 26 patients with thymic carcinoma diagnosed as clinical stage III due to great vessel invasion to study the effects of different treatments on prognosis in real-world.
Extended thymectomy was first proposed by Masaoka in 1981, he defined it as the removal of the extra-capsular fat with the intra-capsular thymus gland, for eliminating as much thymic tissue as possible . In 1996, Masaoka consolidated the concept as resection of the anterior mediastinal fat tissue, which includes the thymus; the operation was performed bluntly from pericardium and pleura. In the procedure of external thymectomy he described, adipose tissues around the upper poles of the thymus, around both brachiocephalic veins, and on the pericardium were resected meticulously. If necessary, the pleural cavity was entered. The borders of resection were the diaphragm caudally, the thyroid gland orally, and the phrenic nerves laterally . Thymectomy in now routinely used for the resection of mediastinal tumors [12,13]. Additionally, extended thymectomy is the most acceptable and efficient therapy for thymic carcinoma .
Involvement of the great vessels has been found to be an independent negative prognostic factor  and favors the onset of recurrence  in thymic carcinoma. Great vessel invasion do not only increases the difficulty and risk of the operation, but can even sometimes completely preclude it. Previous studies have reported on great vessel resection and reconstruction but most of them were case reports [17,18]. Due to the unsatisfactory effect of radiotherapy and chemotherapy, we did our best to perform surgical treatment for the 12 patients in the study. According to our observations, the most commonly invaded vessel is the LIV due to the proximal anatomical feature. Although the operation went fine, it remains a difficult procedure, as can be appreciated from the amount of bleeding and blood transfused during the operation. After reviewing the procedure, we could conclude that the extended thymectomy with blood vessel resection and reconstruction can be completed following a defined procedure; we therefore propose that the operation could be normalized and popularized.
Previous research showed that a tumor diameter larger than 8 cm is a risk factor for recurrence [19,20], while complete resection of a tumor is extremely important for improving prognosis [21–23]. The study of Bacha et al. retrospectively analyzed 89 patients who underwent total or subtotal resection of a primary mediastinal tumor and suggested median sternotomy as an excellent surgical approach . To achieve such a goal and assure safety during the surgery, we adopted median sternotomy for all the patients, which allowed vessel resection and reconstruction and ensured the range of extended thymectomy. At present, there is no clear definition of surgical indications in the latest guidelines, whether thymic carcinoma can be operated depends to a large extent on the surgeon’s appreciation. However, in our retrospective study, there was no significant difference in tumor diameter between the two groups (p=0.249). In real clinical practice, tumor diameter will become one of the factors that influence the surgeon decisions, especially on the issue of resectability.
Rajan et al. indicated that resection of the entire tumor by complete thymectomy and removal of all surrounding mediastinal fat as well as surrounding pleura increased the chances of achieving negative surgical margins . Among the 12 thymic carcinoma patients who underwent operation, all of them had a complete tumor resection with grossly and pathologically confirmed negative resection margins. However, due to the large volume of the tumor, we still can’t certainly exclude the possibility of R1 resection. Some researchers have demonstrated that postoperative radiotherapy reduced thymic malignancy recurrence . In order to reduce postoperative relapse and metastasis, 10 patients received adjuvant therapy, including 6 cases of radiotherapy, 1 case of chemotherapy and 3 cases of radio-chemotherapy. A multicenter study based on a Chinese population found that the lymph node metastasis rate of thymic carcinoma could be as high as 25%, and after intentional lymph node dissection or sampling, the lymph node metastasis rate increased significantly . In this study, the rate of lymph node metastasis was higher (38.8%). We believe that this is associated with the higher overall stage of our cohort, but the above data all suggest the importance of lymph node dissection in thymic carcinoma surgery.
Most patients of the OG had a graft diameter of 8 mm, compared to 12 mm or 10 mm vascular prosthesis used in the studies carried out by Bacha et al. . and Shintani et al. . There is no standard procedure to determine the diameter of artificial vessels. We decided on the diameter for vascular replacement based on the intraoperative evaluation of the invaded vascular. The diameter of artificial blood vessels in the OG was relatively fine due to the Asians figure. However, we experienced 1 patient who had acute thrombosis after surgery and was re-operated with a 12 mm graft replacement, as the reconstructed vessel might have been too small for the patient. Previous studies suggested systematic administration of heparin before vessel replacement [17,18,24], we also gave 2-4 ml heparin during the operation and subcutaneous heparin after the operation to prevent embolism. In addition, oral warfarin was given for 2 months for anticoagulation to maintain the INR between 1.8-2.5. To prevent thrombosis, all grafts were immersed in 125U/ml heparin saline before vessel reconstruction. To date, with the long-term follow-ups, no severe vascular stenosis in the reconstructed vessels was observed.
Chung et al. reported that the median survival for patients with stage III thymic malignancy incompletely or not resected and invading neighboring organs was 26.1 months . Eng et al. concluded that five-year survival rates for thymic carcinoma were approximately 30 to 50 % . Similarly, previous literature reported that the overall 5-year survival rate was 42% for thymic carcinoma patients . In our study, we compared the prognosis between the two subgroups: in OG, 4 patients died and suffered thoracic cavity, liver or bone metastasis by the time of the last follow-up; in contrast, 9 patients died, and 2 patients showed metastasis in the NOG. To the date of the last follow up, the survival rate is 66.67% and 35.71% for the OG and NOG respectively. The median OS of all patients included is 34 months; whereas OS of OG is significantly longer than NOG (48 vs. 26 months, p=0.013). DMFS of OG is also significantly longer than NOG (47 vs. 18 months, p=0.019). The main recurrence pattern of thoracic adenocarcinoma is in situ relapse. Results above suggest that extended thymectomy with vessel resection and reconstruction can significantly improve the prognosis of clinical stage III thymic malignancy with great vessel invasion, and reduce the probability of metastasis.
This study has several limitations. First, due to low incidence of thymic carcinoma, and the study inclusion criteria that were limited to patients with clinical stage III thymic carcinoma, the patient cohort is small. Second, since this is a retrospective analysis, there will be unavoidable selection bias. We had limited the criteria for inclusion to clinical III thymic carcinoma with only vascular invasion to minimize selection bias. Last but not least, this study failed to continue to explore the impact of clinicopathological features, such as tumor diameter, lymph node metastasis, and pathological type, on the prognosis of patients in the OG.