Introduction

Thymic epithelial tumors, including thymoma and thymic carcinoma, are the most common malignant tumors of the anterior mediastinum and are associated with autoimmune disorders [1, 2]. Surgical resection is the most important treatment for these tumors. Even in patients with advanced thymic tumors (Masaoka stage III–IV), the long-term outcomes after surgical resection are significantly better than those in patients who do not undergo surgical resection [3,4,5,6]. Therefore, the possibility of surgical resection should be carefully evaluated for all thymic tumors, regardless of whether they invade the great vessels [7].

Complete resection of mediastinal tumors invading the superior vena cava (SVC) continues to be technically challenging; therefore, nonsurgical treatments such as radiotherapy and chemotherapy are usually preferred. Thymic tumors invading the SVC may be completely resected with a combination of extended resection and artificial vessel reconstruction, which can improve the patient’s quality of life and prolong their survival [8,9,10,11]. However, not all patients with thymic tumors invading the SVC require artificial vessel reconstruction. Given the variation in the site and extent of tumor invasion of the SVC and brachiocephalic vein, there is an urgent need to develop a typing method that can distinguish between the different types of thymic tumors invading the SVC to guide subsequent decisions regarding resection and reconstruction.

This study retrospectively analyzed the data for 57 patients who underwent surgery for thymic tumors invading the SVC at our center between January 2016 and June 2021. Having analyzed their management, we have developed a typing method for management of these tumors according to the location and extent of invasion. This study describes our surgical strategy for thymic tumors invading the SVC.

Methods

Patient information

Fifty-seven patients underwent surgical treatment for thymic tumors invading the SVC in the Department of Thoracic Surgery at Zhongshan Hospital of Fudan University, Shanghai, China between January 2016 and June 2021. Twenty-five patients underwent resection of the left innominate vein only, two underwent partial resection and repair of the SVC, and 30 underwent artificial vessel reconstruction between the brachiocephalic vein and the right atrial appendage followed by resection of the tumor and SVC. The patient demographic and clinical characteristics are shown in Table 1. The study protocol was approved by the Zhongshan Hospital Research Ethics Committee (No. B2021-781). Informed written consent for the publication of the study data was obtained from all patients whose data were included.

Table 1 Patient demographics and clinical characteristics
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Zhongshan typing method for thymic tumors invading the SVC

We have developed the following Zhongshan typing method for management of thymic tumors invading the SVC based on the location and extent of invasion (Fig. 1, Table 2):

Fig. 1
figure 1

Schematic diagram of the Zhongshan method used to type thymic tumors invading the superior vena cava. A Type I: If the tumor invades only the LIV or RIV, only the LIV (A1) or RIV (A2) is removed. B Type II: If the tumor invades less than 30% of the circumference of the SVC, only the part of the SVC that is invaded by the tumor is removed, and the defect is repaired by direct suturing or using patches. C Type III: If the tumor invades more than 30% of the circumference of the SVC, a vascular graft between a brachiocephalic vein and the RAA is performed first (C1) followed by extended resection of the tumor and the invaded portion of the SVC. (C2) Type IIIa: If the tumor invades the SVC above the AAV, the AAV is preserved. (C3) Type IIIb: If the tumor invades the SVC at or below the AAV, the AAV is resected. AAV, azygos vein; LIV, left innominate vein; RAA, right atrial appendage; RIV, right innominate vein; SVC, superior vena cava

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Table 2 Zhongshan typing of thymic tumors invading the superior vena cava
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Type I

If the tumor exclusively invades the left or right innominate vein and does not invade the main trunk of the SVC, resection of the left innominate vein or right innominate vein is sufficient, and artificial reconstruction is not required (Fig. 1A).

Type II

If the tumor invades less than 30% of the circumference of the SVC, resection of the SVC wall at least 2 mm from the tumor margin should be sufficient, and the defect in the SVC should be repaired by direct suturing or using patches (Fig. 1B).

Type III

If the tumor invades more than 30% of the circumference of the SVC, an artificial reconstruction between the brachiocephalic vein and right atrial appendage should be performed first (Fig. 1C1), followed by extended resection of the tumor and the invaded portion of the SVC. Type III tumors can be further divided into two subtypes depending on whether the tumor invades the azygos vein as follows.

Type IIIa: if the tumor invades the SVC above the azygos vein, the azygos vein should be preserved (Fig. 1C2).

Type IIIb: if the tumor invades the SVC at or below the azygos vein, the azygos vein should be resected (Fig. 1C3).

Statistical analysis

Descriptive and survival analyses were performed using SPSS software (version 20; IBM Corp., Armonk, NY, USA).

Results

Clinical pathological data

Twenty-five patients with type I tumors underwent thymectomy combined with resection of the left innominate vein (Fig. 2A). Twelve of these cases were resected by subxiphoid thoracoscopy and 13 by median sternotomy. The diagnosis was thymoma in 15 cases and thymic carcinoma in 10. According to the Masaoka staging system, 15 cases were stage IIIb, six were stage IVa (combined with pleural metastasis), and four were stage IVb (combined with lymph node metastasis or lung metastasis). Nine patients also had myasthenia gravis. Nine patients received preoperative neoadjuvant therapy and 17 received postoperative adjuvant therapy (Table 1). The median tumor size was 6.0 cm (interquartile range [IQR] 4.5, 8.0). The median operation time was 136 min (IQR 119, 169) and the median intraoperative blood loss was 150 mL (IQR 50, 200). The median duration of postoperative tube drainage was 4 days (IQR 4, 7), and the median postoperative hospital stay was 6 days (IQR 5, 8) (Table 3).

Fig. 2
figure 2

Representative cases for which the Zhongshan method was used to type thymic tumors invading the superior vena cava. A Thymectomy combined with resection of the left innominate vein by subxiphoid thoracoscopy. B Resection of part of the superior vena cava invaded by the tumor, with repair of the superior vena cava by direct suturing. C Extended tumor resection combined with vascular reconstruction between the left innominate vein and right atrial appendage. D The artificial vessel (yellow arrows) remained unobstructed 30 months after surgery. E The artificial vessel (yellow arrows) was obstructed 20 months after surgery

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Table 3 Surgical data of 57 patients with thymic tumors invading the superior vena cava
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All type II and III tumors were resected by median sternotomy. Two patients with type II tumors underwent thymectomy combined with partial resection and repair of the SVC (Fig. 2B); both these patients had a diagnosis of thymoma (Masaoka stage IIIb) and myasthenia gravis, and neither received preoperative or postoperative adjuvant therapy (Table 1).

Thirty patients with type III tumors underwent artificial revascularization between a brachiocephalic vein and the right atrial appendage followed by extended resection of the tumor and the tumor-invaded SVC (Fig. 2C). Artificial revascularization of the left innominate vein–right atrial appendage was performed in 27 cases and of the right innominate vein–right atrial appendage in three cases. Eleven of the 30 patients with type III tumors had a diagnosis of thymoma and 19 had a diagnosis of thymic carcinoma. Twenty-five patients were Masaoka stage IIIb and five were stage IVa (combined with pleural metastasis). Three patients also had myasthenia gravis. Sixteen patients received preoperative neoadjuvant therapy and 13 received postoperative adjuvant therapy (Table 1). The median tumor size was 6.0 cm (IQR 5.0, 8.4). The median operation time was 210.5 min (IQR 193, 250), and the median intraoperative blood loss was 650 mL (IQR 400, 1 000). The median duration of postoperative tube drainage was 10 days (IQR 7.3, 13), and the median postoperative hospital stay was 13.5 days (IQR 10, 18.8) (Table 3).

Perioperative complications

No serious complications occurred in the patients with type I or II tumors (Table 4). Complications occurred mainly in patients with type III tumors. Three of the 30 patients with type III tumors died. Two deaths were probably caused by thromboembolic complications and one was attributable to postoperative bleeding. Two patients underwent repeat surgery for postoperative bleeding and sternal dehiscence. One patient developed myasthenia gravis crisis and underwent tracheotomy and ventilator-assisted treatment. Surgical site infection occurred in one case and improved after wound care (Table 4).

Table 4 Perioperative complications in 57 patients with thymic tumors invading the superior vena cava
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Postoperative anticoagulation and patency of artificial blood vessels

Patients with type I tumors were not treated with postoperative anticoagulants and those with type II tumors were treated with short-term postoperative anticoagulation using aspirin. Patients with type III tumors received dual antiplatelet therapy (aspirin + clopidogrel), warfarin, or rivaroxaban for long-term anticoagulation after surgery. Obstruction of the artificial blood vessel was found in one patient 20 months after surgery, but no short-term or long-term artificial blood vessel obstruction was detected in the remaining 29 patients through to the final follow-up date (Fig. 2D, E). The long-term artificial blood vessel patency rate was 96.7%.

The prognosis

All patients were followed up closely after surgery until January 2022. The median follow-up time for type I patients was 19 months; their 5-year progression-free survival and overall survival rates were 82.1% and 88.9%, respectively (Fig. 3A, B). The median follow-up for type III patients was 22 months. The 5-year progression-free survival and overall survival rates were 34.8% and 72.8%, respectively, in these patients (Fig. 3C, D). The median follow-up for all 57 patients was 22 months, with respective 5-year progression-free survival and overall survival rates of 59.6% and 81.2% (Fig. 3E, F).

Fig. 3
figure 3

Prognosis of patients with thymic tumors invading the superior vena cava. Progression-free survival rate (A) and overall survival rate (B) of patients with type I tumors. Progression-free survival rate (C) and overall survival rate (D) of patients with type III tumors. Progression-free survival rate (E) and overall survival rate (F) of patients with type I–III tumors

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Discussion

This research allowed us to develop a method for classifying thymic tumors invading the SVC into three specific types, which allows for different surgical procedures to be performed depending on type. We have called this method “Zhongshan typing for thymic tumors invading the SVC” and hope that it will provide a decision-making reference for tumor resection and reconstruction of the SVC and serve as a common term for academic exchange.

This typing method is important in patients with thymic tumors invading the SVC in terms of optimal surgical treatment. Based on our findings, we suggest that patients with type I tumors are candidates for more aggressive surgical resection because they are likely to have fewer complications and their prognosis is better than that in patients with type III tumors. Moreover, only the left innominate vein is resected, which has little long-term effect. Thymic tumors can potentially be resected by a subxiphoid thoracoscopic approach if they invade only the left innominate vein [12]. A thymic tumor invading the right innominate vein alone is a rare occurrence and increases the risk associated with thoracoscopic surgery; therefore, median sternotomy is recommended. Imaging such as contrast-enhanced computed tomography or magnetic resonance imaging of the chest is very important for typing patients. However, typing based on imaging needs to be adjusted according to the actual situation during the procedure.

A type II tumor is usually identified during the procedure based on the extent of involvement of the SVC circumference. Direct suturing of the SVC is indicated only in cases where the SVC defect is small. We have found it difficult to repair or shape the SVC in patients who have 30% involvement of the SVC by simple partial blocking of the lateral wall of the SVC. Therefore, a large SVC defect must be repaired with a patch such as autologous pericardium to avoid stenosis [13]. Patients with greater SVC involvement could also be managed by partial resection and autologous pericardial repair, but this often requires temporary intraoperative shunting. We determined this 30% threshold mainly to ensure safe surgical margins and the rationality of the procedure. However, this finding needs to be confirmed by more clinical experience, considering that surgical skills vary from surgeon to surgeon.

For patients with type III tumors, we recommend artificial reconstruction between the brachiocephalic vein and right atrial appendage followed by extended resection of the thymic tumor. This strategy benefits both the patient and the surgeon. For patients, complete blockage of the SVC can be avoided during surgery, thereby reducing the impact of surgery on hemodynamics and impairment of brain function. For thoracic surgeons, this strategy allows sufficient time to perform the artificial vessel anastomosis and reduces the requirement for speed in terms of the artificial vessel anastomosis.

The approach used for vascular reconstruction after resection of the SVC depends on the extent of tumor invasion and the condition of the patient's blood vessels. Commonly used vascular reconstruction methods include left innominate vein–right atrial appendage bypass, right innominate vein–right atrial appendage bypass, right innominate vein–SVC bypass. and left and right innominate vein–right atrial appendage Y-bypass [8,9,10]. We recommend a single vascular reconstruction of a left or right innominate vein–right atrial appendage bypass because a single artificial vessel is sufficient for return of blood based on our findings. Owing to the anatomical relationship, right innominate vein–right atrial appendage bypass allows for better placement of the artificial vessel and better return of blood and should be preferred for patients with small tumors and a sufficiently long normal right innominate vein. However, thymic tumors that invade the SVC are often large, making it difficult to perform a vascular anastomosis between the right innominate vein and the artificial vessel without removing the tumor specimen. In contrast, the left innominate vein crosses the aortic arch and has a long course, so it is easier to mobilize when it is not completely invaded by the tumor. Even if the tumor is not removed, the left innominate vein can still be easily anastomosed to the artificial vessel under direct vision. Therefore, we recommend left innominate vein–right atrial appendage bypass as a priority for patients whose tumors do not completely invade the left innominate vein.

In patients with type III tumors, it is important to note that the SVC should be blocked before resection of the thymic tumor to prevent tumor thrombus in the SVC from detaching and causing embolism. It is also important to note that the right phrenic nerve usually needs to be removed during this procedure, so the left phrenic nerve must be protected to avoid the serious complications caused by bilateral phrenic nerve injury [14]. Although the right phrenic nerve was removed in most of our patients with type III tumors, serious phrenic nerve complications were rare, probably because the right phrenic nerve had been invaded by the tumor and had already lost its function. Type III is divided into IIIa and IIIb according to whether the azygos vein can be preserved; the main consideration in this regard is the impact of retention of the collateral circulation on the safety of surgery.

Our typing method has some limitations. First, this method is mainly based on manifestations seen on imaging, such as contrast-enhanced computed tomography or magnetic resonance imaging of the chest, which may differ from the actual situation encountered during the procedure [15]. Second, it does not account for venous collaterals, which can sometimes influence the surgical strategy [16]. Third, it is based only on tumor invasion of the SVC and does not consider other tumor-related factors, such as tumor size, pathological type, and invasion of the surrounding tissues, such as the aorta, pulmonary artery, and heart. If the tumor has invaded these structures, we generally perform palliative tumor resection instead of radical tumor resection supplemented by postoperative radiotherapy. Finally, this typing system is unsuitable for patients with variant upper vena cava anatomy or a double SVC. In these rare cases, we propose a classification system based on the SVC, mainly considering that tumor invasion into the SVC is the most likely type of invasion for radical resection, which is similar to the Bismuth classification for cholangiocarcinoma [17].

Furthermore, for various reasons, some patients did not receive postoperative adjuvant radiotherapy. Most patients with myasthenia gravis had concerns about radiotherapy because of its potential to worsen their symptoms [18]. Some patients refused postoperative radiotherapy after complete tumor resection, especially those who had already received preoperative neoadjuvant therapy.

In summary, our typing method can facilitate development of a surgical strategy for complete resection of a thymic tumor invading the SVC, thereby improving the patient’s quality of life and survival time.