Thymectomy

INTRODUCTION — Surgical resection of the thymus gland (ie, thymectomy) is used to treat thymic tumors (thymoma, thymic carcinoma, and thymic neuroendocrine [carcinoid] tumors) and for the management of myasthenia gravis. Preoperative imaging evaluation is important to determine the likelihood of resectability of a thymic tumor and whether one should consider induction therapy prior to attempting resection. Thymectomy has traditionally been performed via a median sternotomy, but minimally invasive techniques are increasingly applied, primarily using unilateral or bilateral video or robotic-assisted thoracoscopic techniques. A minimally invasive transcervical technique (with or without video assistance) is also described for the surgical treatment of nonthymomatous myasthenia gravis but is less commonly used.

The general approach to thymectomy, including evaluation, preparation, surgical techniques, and surgical outcomes, is reviewed. Specific indications for thymectomy and the timing of thymectomy relative to medical management strategies are provided in separate topic reviews.

●Thymoma, thymic carcinoma, and thymic neuroendocrine tumors – Thymectomy is indicated for resection of tumors including thymoma, thymic carcinoma, and thymic neuroendocrine tumors. Thymoma is considered malignant and should be resected even though it generally has an indolent growth pattern. (See "Clinical presentation and management of thymoma and thymic carcinoma" and "Thymic neuroendocrine (carcinoid) tumors".)

●Myasthenia gravis – Thymectomy is used to manage thymoma associated with myasthenia gravis and is also a validated treatment for those with myasthenia gravis who do not have thymoma (ie, nonthymomatous myasthenia gravis) [1]. (See "Overview of the treatment of myasthenia gravis" and "Role of thymectomy in patients with myasthenia gravis".)

PREOPERATIVE EVALUATION AND PREPARATION — All patients being assessed for thymectomy should undergo a thorough history and physical exam. History should include any past history of radiation to the neck or chest, and prior surgery in the neck, mediastinum, or thorax. For patients with an anterior mediastinal mass, differentiating a thymic mass from other anterior mediastinal tumors, including thyroid tumors, germ cell tumors, and lymphoma, requires specific considerations. (See "Approach to the adult patient with a mediastinal mass".)

On physical examination, the patient should be assessed for adenopathy that would raise suspicion for metastatic disease or lymphoma, as well as any physical characteristics that may suggest a benefit for one surgical approach over another, such as limited ability to extend the neck, which would make a transcervical approach difficult, or chest wall deformity or severe obesity that could complicate port placement. (See "Overview of minimally invasive thoracic surgery", section on 'Patient selection'.)

Preoperative studies include cross-sectional imaging, typically in the form of high-resolution computed tomography with and without intravenous contrast, to aid in diagnosis, clinical staging, and determination of resectability; pulmonary function tests to help stratify risk for pulmonary complications and to serve as a baseline for postoperative comparison; routine baseline laboratories (eg, complete blood count, chemistry, and coagulation studies); and electrocardiography or other studies, as indicated. Other laboratory studies, such as thyroid function tests, tumor markers (alpha fetoprotein and beta-hCG), or myasthenia gravis antibodies (eg, anti-AChR, anti-SM, anti-MuSK), can also be obtained if they will help facilitate diagnosis. (See "Approach to the adult patient with a mediastinal mass", section on 'Laboratory studies'.)

Confirm resectability and tumor staging — There are no consensus guidelines on determination of unresectability. Preoperative cross-sectional imaging help determine potential resectability, specifically evaluating whether intrathoracic structures are invaded by the tumor. If imaging studies were performed more than eight weeks prior to the planned surgery, they may need to be repeated, depending upon the anticipated aggressiveness of the tumor.

Computed tomography (CT) is useful for showing the characteristics of a thymic tumor and the extent of infiltration of nearby structures. Thymoma is typically well circumscribed and relatively uniform, while the radiologic characteristics of thymic carcinoma can include irregular borders or cystic, necrotic, or calcified elements. The extent of infiltration can also be determined (eg, intact thymic capsule versus extension into mediastinal fat or pleura, fat planes separating the tumor from major structures versus obvious invasion through these structures). Positron emission tomography (PET) scan is an additional imaging modality that can provide insight on the metabolic activity of the tumor. (See "Clinical presentation and management of thymoma and thymic carcinoma", section on 'Diagnostic evaluation'.)

The Masaoka-Koga classification (table 1) has been the most commonly used and reported staging system for thymic epithelial tumors [2]. The eighth edition of the American Joint Committee on Cancer (AJCC) tumor, node, metastases (TNM) classification, which is applicable to all thymic malignancies, including neuroendocrine tumors, is being used more frequently worldwide (table 2) [3]. (See "Clinical presentation and management of thymoma and thymic carcinoma", section on 'Staging' and "Thymic neuroendocrine (carcinoid) tumors", section on 'Staging classification'.)

●Masaoka stage I and II (corresponding to AJCC stage I/II) tumors are treated with thymectomy.

●Masaoka stage III (AJCC stage IIIa) tumors may be treated with thymectomy if judged to be completely resectable by preoperative evaluation. Otherwise, induction chemotherapy followed by surgery can be used. (See "Clinical presentation and management of thymoma and thymic carcinoma", section on 'Resectable disease' and "Clinical presentation and management of thymoma and thymic carcinoma", section on 'Potentially resectable disease'.)

●Masaoka stage IVa/b (AJCC stage IIIb/IVa/IVb) tumors are generally not considered resectable. They can be considered for resection in selected cases but certainly should be discussed in a multidisciplinary setting. (See "Clinical presentation and management of thymoma and thymic carcinoma", section on 'Resectable disease' and "Clinical presentation and management of thymoma and thymic carcinoma", section on 'Potentially resectable disease' and "Clinical presentation and management of thymoma and thymic carcinoma", section on 'Unresectable disease'.)

The utility of cross-sectional imaging studies to predict staging/resectability for higher-grade tumors has been assessed in several studies:

●In a review of 133 patients (80 Masaoka stage I or II and 53 Masaoka stage III or IV) who underwent surgical resection for thymoma, 17.3 percent had an incomplete surgical resection [4]. The preoperative CT characteristics that significantly correlated with an incomplete surgical resection on univariate analysis included a lobulated tumor contour, ≥50 percent abutment of the circumference of an adjacent vessel, thoracic lymphadenopathy, adjacent lung changes, and pleural nodularity. Tumor size was also significantly larger for incompletely compared with completely resected groups (9.7 versus 6.9 cm). However, with multivariate analysis, only the degree of abutment of adjacent vessels and pleural nodularity were independent predictors of incomplete resection.

●In a review of 99 patients referred for evaluation of thymoma by CT, univariate analysis showed that Masaoka stage III/IV was associated with tumors >7 cm, lobulated tumor contour, heterogeneous tumors, calcified tumors, infiltration of mediastinal fat, greater than or equal to 50 percent abutment of the circumference of an adjacent vessel, adjacent lung changes, pleural effusion, pleural nodularity, and young age [5]. On multivariate analysis tumor size >7 cm, infiltration of surrounding fat and lobulated tumor contour were significantly associated with stage III/IV disease.

●No large trials or strong established guidelines are available regarding the utility of magnetic resonance (MR) imaging over CT scan. MR may be more useful than CT for distinguishing thymic carcinoma from thymoma [6]. In addition, if there is a question of great vessel involvement on CT scan along with other radiographic features that are concerning for a higher tumor stage, we commonly obtain MR to further confirm imaging findings, and to establish operative expectations with the patient or other caregivers. Cine MRI may have a role when there is concern for myocardial invasion [7]. MR would also be preferable over noncontrast CT scan for patients with contraindications to contrast CT scan (eg, severe intravenous contrast allergy), particularly with respect to identifying great vessel invasion.

●With regard to PET, in an analysis of the International Thymic Malignancy Interest Group (ITMIG) among 154 patients with thymic tumors, higher maximum standardized uptake value (SUVMax) was significantly associated with more aggressive histologic type and with more advanced pathologic Masaoka stage [8].

While cross-sectional imaging provides detailed clinical staging that directs surgical resection, further extension of disease may be found intraoperatively, and the final staging (operative and pathologic) determines the prognosis and the need for adjuvant chemotherapy or radiation. (See "Clinical presentation and management of thymoma and thymic carcinoma", section on 'Postoperative radiation therapy' and "Clinical presentation and management of thymoma and thymic carcinoma", section on 'Chemotherapy regimens'.)

Utility of diagnostic thoracoscopy — Involvement of the pericardium, lungs, innominate vein, or sternal periosteum may be seen in preoperative imaging, and these cases must be carefully assessed for feasibility of achieving an R0 resection. Over 50 percent circumferential abutment of tumor to vascular structures is associated with vascular involvement and may require vascular resection. The extent of resection may warrant a traditional transsternal approach, especially with vascular involvement. When it is unclear whether these structures are involved, diagnostic thoracoscopy is a reasonable initial approach; however, intraoperative evaluation is the only way to know true resectability in borderline cases and as such, these cases should generally be approached open.

Biopsy — Preoperative biopsy is not required for patients with small tumors that have no evidence of invasion beyond the thymus and that are radiographically suspicious only for thymoma. (See "Clinical presentation and management of thymoma and thymic carcinoma", section on 'Diagnostic evaluation'.)

Preoperative biopsy is useful to confirm diagnosis, particularly in cases that will undergo induction therapy rather than initial surgery. In these cases, biopsy can be performed using a CT-guided percutaneous approach, or anterior mediastinotomy. Transpleural biopsy should be avoided as it can be associated with intrapleural tumor seeding. (See "Approach to the adult patient with a mediastinal mass", section on 'Biopsy'.)

Pulmonary function testing — Preoperative pulmonary function studies should be obtained in all patients to estimate the extent of respiratory compromise following division of the phrenic nerve, if this is anticipated, and to predict and help manage perioperative myasthenic crises. (See "Evaluation of perioperative pulmonary risk" and "Evaluation of cardiac risk prior to noncardiac surgery" and "Anesthesia for the patient with myasthenia gravis", section on 'Preoperative evaluation'.)

While efforts are made to avoid iatrogenic phrenic injury during thymus resection, tumor invasion of the phrenic nerve may require its resection in select cases when this would be necessary to achieve complete microscopic resection. In such cases, assessment of preoperative phrenic nerve function with a sniff test (fluoroscopic, ultrasonographic) could be useful. While generally not recommended, another approach includes planned (or urgent) phrenic nerve reconstruction if there is a high likelihood that both nerves are involved. Phrenic nerve repair extends operative time, and requires microsurgical expertise, which is often not available. Surgical referral for possible phrenic nerve repair can be considered where such expertise is available. (See "Surgical treatment of phrenic nerve injury", section on 'Surgical referral' and 'Handling the phrenic nerves' below.)

Evaluation for myasthenia gravis — Because of the risks associated with surgery, all patients with thymic tumors, particularly those with thymoma, should be evaluated for evidence of myasthenia gravis; if signs or symptoms are present, these should be treated medically prior to surgery. In a review of the International Thymic Malignancy Interest Group database, 38 percent of patients with thymoma had myasthenia gravis compared with less than or equal to 5 percent for thymic carcinoma and thymic neuroendocrine tumor [9]. (See "Diagnosis of myasthenia gravis".)

All patients with myasthenia gravis who are being considered for surgery require a complete preoperative evaluation by a multidisciplinary team involving the surgeon, anesthesiologist, neurologist, and pulmonologist. Patients with myasthenia are at increased risk for perioperative complications due to potentially compromised respiratory function, but operative mortality is generally less than 1 percent with optimal management [10]. Perioperative medical management of myasthenia gravis patients, including anticholinesterase inhibitors, intravenous immunoglobulin, plasmapheresis, immunosuppressants, and anesthesia, is discussed in detail separately. (See "Anesthesia for the patient with myasthenia gravis", section on 'Preoperative evaluation' and "Role of thymectomy in patients with myasthenia gravis", section on 'Perioperative management'.)

Important perioperative surgical considerations include the following:

●NO patient in myasthenic crisis is a candidate for surgery. Symptoms must be under control at time of surgery.

●Plasmapheresis may induce coagulation abnormalities by removing coagulation factors and complement components (C3 and C4), which may increase bleeding risk and affect the timing of surgery.

●Ideally, steroid dosages should be minimized to optimize postoperative wound healing, but many will require perioperative stress dosing.

Evaluation for paraneoplastic syndromes — While the most common paraneoplastic syndrome associated with thymoma is myasthenia gravis, there are several other paraneoplastic syndromes also associated with thymoma. This includes pure red cell aplasia and Good syndrome. The need to evaluate for these less common syndromes is not standardized, but these can be considered in a case-by-case basis. (See "Clinical presentation and management of thymoma and thymic carcinoma", section on 'Paraneoplastic disorders'.)

ANESTHESIA AND PERIOPERATIVE CARE — Anesthesia for surgery in patients with an anterior mediastinal mass is reviewed separately. (See "Anesthesia for patients with an anterior mediastinal mass" and "Anesthesia for the patient with myasthenia gravis".)

●A first-generation cephalosporin is adequate, unless hospital-specific antibiograms indicate other antibiotics (table 3) [11-13]. Aminoglycoside antibiotics are contraindicated in patients with myasthenia gravis since they increase neuromuscular blockade. (See "Antimicrobial prophylaxis for prevention of surgical site infection in adults", section on 'Thoracic surgery'.)

●Patients routinely receive thromboprophylaxis in the form of subcutaneous unfractionated or low-molecular-weight heparin. (See "Prevention of venous thromboembolic disease in adult nonorthopedic surgical patients".)

PROCEDURE — Surgical management of myasthenia gravis involves resection of the entire thymus gland. For patients with thymoma, thymic carcinoma, or neuroendocrine tumor, thymectomy is the initial treatment for those in whom a complete R0 resection is considered feasible. Traditionally, total thymectomy has been advocated in the management of early-stage thymomas as well. The potential role of partial thymectomy is discussed below. (See 'Partial thymectomy for early-stage thymoma' below.)

Anesthesia for thymectomy is discussed separately. (See "Anesthesia for patients with an anterior mediastinal mass".)

Anatomy — The thymus is an encapsulated bilobed gland that lies in the anterior mediastinum (figure 1). Each lobe contains both superior and inferior horns and each extends laterally towards the phrenic nerve on each side (figure 2 and figure 3).

The standard boundaries of a radical thymectomy are the phrenic nerves laterally, diaphragm inferiorly, and thyrothymic ligaments and innominate vein superiorly. The superior horn may extend up into the neck deep to the sternohyoid muscle. The mediastinal and cervical adipose tissue may contain variable amounts of thymic tissue [14].

The blood supply to the thymus is derived from branches off the internal mammary arteries, inferior thyroid arteries, and pericardiophrenic arteries. Venous drainage is mainly via tributaries into the innominate vein and sometimes directly into the superior vena cava.

Incisions and surgical approach — Surgical approaches to thymectomy use either a median sternotomy (transsternal), multiple small incisions for port placement (traditional video-assisted thoracoscopic surgery [VATS] or robotic-assisted thoracoscopic surgery [RATS]), a subxiphoid incision (uniportal or multiport; VATS or RATS), or a low horizontal neck incision (transcervical; with or without video assistance). The approach should maximize resection of thymic tissue while avoiding damage to the recurrent laryngeal, left vagus, and phrenic nerves. For thymoma or thymic tumor resection, the extent of tumor, including any degree of invasion or adhesion of the tumor to contiguous structures, dictates the best approach [15]. Prior thoracic surgery should also be a consideration in planning surgical approach.

Resection of the mediastinal pleura, pericardium, adjacent lung, innominate vein, or phrenic nerve (if unilateral) is sometimes required to achieve a total resection with histologically negative margins. Surgical judgment is critical for determining invasion of adjacent structures. Long-term survival following tumor resection depends upon the completeness of surgical resection [15,16]. (See 'Confirm resectability and tumor staging' above and 'Extended thymectomy' below and "Clinical presentation and management of thymoma and thymic carcinoma", section on 'Prognosis'.)

The four approaches vary in the location/extent of the incisions used to remove the thymus gland. They also vary in the extent that the extracapsular mediastinal and cervical fat can be removed. These include the following [17-21]:

●Transsternal thymectomy – The use of a median sternotomy incision (figure 4) has been considered the standard approach for thymectomy (ie, extended transsternal thymectomy, combined transcervical-transsternal thymectomy). It is often required for large tumors and tumors invading adjacent structures and provides excellent exposure of the anterior mediastinum and thymus [22-26]. It also allows full exploration into the neck to completely remove all thymic tissue and associated fat. (See 'Transsternal thymectomy' below.)

●Extended cervical thymectomy – Compared with simple cervical thymectomy, which removes only parts of the upper thymus, extended cervical thymectomy is approached through a transverse neck incision. This approach requires brief hospitalization, often one day, and leaves a relatively small scar (figure 5) [27]. Extended cervical thymectomy is an approach that is used by surgeons trained in this technique but is an unfavorable approach for patients who are unable to extend their necks. This technique uses a special manubrial retractor for improved exposure and resection in the mediastinum, often with the associated use of mediastinoscopy. Sternotomy may be needed for access to control bleeding. Some argue that this approach may not adequately expose the entire thymus, thereby increasing the risk of residual thymus being left behind. However, for patients with myasthenia gravis, clinical improvement similar to transsternal thymectomy has been reported in several series [19,28-30]. This approach minimizes the impact of postoperative pain on ventilatory reserve [29,31]. The majority of reported experiences using this approach describe its use exclusively in the treatment of nonthymomatous myasthenia gravis; its role in the resection of small thymomas (less than 3 cm) is anecdotal at best. (See 'Transcervical thymectomy' below.)

●Minimally invasive thymectomy – Minimally invasive thymectomy (MIT), such as using video-assisted thoracoscopic or robotic-assisted approaches, is performed through small incisions from either the right or left side with the patient in slight decubitus or full decubitus position (figure 6) [32]. Robotic-assisted thoracoscopic surgery is appealing for many surgeons because of the advantages of the robotic platform for performing dissection in a confined space. Three-dimensional optics and gas insufflation also facilitate the conduct of surgery. Short- and mid-term data appear favorable [33-36]. MIT requires careful patient selection and is generally associated with low morbidity and mortality [22,32,33,37-41]. (See 'Minimally invasive thymectomy' below.)

●Subxiphoid thymectomy – While not a common approach in Western countries, the subxiphoid approach has gained popularity in several Asian countries, including Japan and South Korea. The subxiphoid approach can be considered another form of MIT but is truly a unique approach that was first described in 1999 becoming more popular and refined over the next 10 to 15 years [42-44]. The subxiphoid approach has the advantages of an optimized view of the phrenic nerves bilaterally and decreased postoperative pain. Resection of advanced tumors, including reconstruction of vascular structures (innominate vein), have been described. The robotic subxiphoid approach has become the author's standard approach for extended thymectomy including large (>10 cm) tumors [44].

Open versus minimally invasive thymectomy — MIT has been increasingly adopted for patients with thymic tumors and for those with myasthenia gravis. For thymoma or thymic carcinoma, there is no consensus whether open transsternal thymectomy is better than MIT, and the issue awaits an appropriately designed, prospective trial. Despite the increased use of minimally invasive techniques, some thoracic surgeons still prefer transsternal thymectomy [45].

In general, MIT is reserved for stage I to II thymomas and thymic carcinomas less than 5 cm in diameter, and for nonthymomatous myasthenia gravis, although there is increasing experience with resection of larger tumors [46].

Several meta-analyses have evaluated studies comparing the perioperative aspects of open versus MIT [47-51]. There is no doubt that MIT is associated with less perioperative morbidity and shorter lengths of hospital stay. As an example, in one series of 95 patients with myasthenia gravis, the mean length of hospital stay was significantly shorter with video-assisted thoracoscopic surgery compared with a transsternal approach (1.9 versus 4.6 days) [27,33]. In addition, approaches that avoid splitting the sternum avoid potential post-sternotomy complications [35].

Completeness of tumor resection — Completeness of resection (R0) is the most important long-term prognostic indicator in thymoma and thymic carcinoma, and incompleteness (R1-R2 resection) at time of thymectomy correlates with local recurrence [52-56].

In a review of the International Thymic Malignancy Interest Group (ITMIG), 2514 patients underwent thymectomy for thymoma between 1997 and 2012 (82 percent open surgery, 18 percent minimally invasive) [18]. R0 resection was achieved in 86 percent of the open thymectomy group and in 94 percent of the MIT group. In propensity-matched analysis for each group, the rate of R0 resection (96 percent) did not differ significantly. Multivariate analysis found that lower Masaoka stage, total thymectomy, and the absence of radiotherapy were factors independently associated with R0 resection. However, since meaningfully evaluating local recurrence rates following thymectomy for thymoma requires long follow-up periods (>10 years), data comparing local recurrence rates are not mature, since MIT for thymoma is a relatively young procedure.

Relief of myasthenic symptoms — For nonthymomatous myasthenia gravis, there are no convincing data showing superior efficacy or long-term remission rates for one of these approaches over another [57]. While all patients underwent median sternotomy in the Thymectomy trial for myasthenia gravis [1], several series comparing VATS with other approaches have promising results for long-term relief of myasthenic symptoms or low recurrence rates of thymoma [32,33,37,41]. (See "Role of thymectomy in patients with myasthenia gravis", section on 'Generalized AChR-positive myasthenia'.)

Conversion rates — Most of the data on conversion rates are based on case series. Rates of conversion from MIT to open thymectomy in the literature range from 0 to 7 percent [40,58,59]. In one retrospective cohort comparing 79 thoracoscopic thymectomies and 74 robotic thoracoscopic thymectomies, 1/79 (1.3 percent) and 1/74 (1.4 percent) patients required conversion to open thymectomy, respectively [60].

Conversion rates for transcervical thymectomy vary from 0 to 19 percent. In one series of 92 patients, 8 conversions (8.7 percent) were reported with 6/8 converted to open and 2/8 converted to thoracoscopic resection [28]. In a separate review, 23 out of 120 (19 percent) patients required a partial sternotomy [61]. In a review of nonthymomatous myasthenia gravis, there were no conversions among 100 consecutive patients [19].

Perioperative outcomes — Perioperative death is rare with no reported perioperative deaths in a retrospective review of 2514 patients in the ITMIG database who underwent open or MIT between 1997 and 2012.

Compared with open thymectomy, MIT has been associated with shorter hospital stays [17,19,33,37,58,62], shorter intensive care unit length of stay [58], lower operative blood loss [58,59], decreased postoperative pain [63], and similar operating room times [58]. As an example, in one series of 95 patients with myasthenia gravis, the mean length of hospital stay was significantly shorter with VATS compared with a transsternal approach (1.9 versus 4.6 days) [33]. In another series of 151 extended transcervical thymectomies, most procedures were performed without the need for overnight hospitalization, and the operative major complication rate was <1 percent [27]. In addition, approaches that avoid splitting the sternum avoid potential sternotomy complications. (See 'Surgical site infection and mediastinitis' below.)

MIT is also associated with improved postoperative pulmonary function. In one small trial, those randomly assigned to MIT had complete recovery of pulmonary function by postoperative day 3 compared with only 55 percent of those with sternotomy [46].

Extent of resection

Extended thymectomy — Extended thymectomy involves complete removal of the gland (en bloc), including resection of all four thymic lobes, and perithymic tissue. Intraoperatively, it is impossible to differentiate the thymus from adipose tissue, and thus a total resection requires removal of all tissue anterior to the pericardium from the innominate vessels to the diaphragm, and from the left phrenic nerve to the right phrenic nerve (ie, extended resection). The extent of resection should be just as complete for thymomas as with thymic carcinomas given that carcinomas often appear benign even on pathologic examination. The anatomic limits of the thymus gland are reviewed above. (See 'Anatomy' above.)

Debulking surgery for a thymoma, thymic carcinoma, or thymic neuroendocrine tumor is a controversial topic since it is not curative, and discussion at a multidisciplinary conference is recommended for patients with borderline imaging studies. In a review that included 13 observational studies, among 314 patients who underwent debulking surgery, overall survival was improved for those undergoing debulking surgery compared with surgical biopsy (54.8 versus 45.2 percent; hazard ratio 0.45, 95% CI 0.34-0.61) [64].

Palliative resection can also be considered if a hormonal secretory condition such as Cushing syndrome, hypercalcemia, or carcinoid syndrome is debilitating. (See "Thymic neuroendocrine (carcinoid) tumors", section on 'Clinical presentation'.)

Partial thymectomy for early-stage thymoma — The role of lesser resections in treating Masaoka stages I to II thymomas not associated with myasthenia gravis is a subject of debate. Three retrospective series that compared the outcomes of partial thymectomy (thymomectomy) with total (ie, extended) thymectomy have shown no oncological differences in survival or rates of recurrence [65-67]. In addition, the rates of developing myasthenia gravis after resection of the thymoma were similar. The largest of these series compared 100 partial thymectomies via mostly anterolateral thoracotomy (n = 58) or VATS (n = 41) with 73 total thymectomies, 72 of which were performed via sternotomy [67]. With a mean follow-up of 9 years in both groups, survival rates at 10 years were 94 percent after partial thymectomy and 86 percent after total thymectomy. Local recurrence rates were 2 percent after partial thymectomy and 5 percent after total thymectomy. Myasthenia gravis developed in 3 percent of patients after partial thymectomy and 8 percent after total thymectomy. These limited data suggest that total (ie, extended) thymectomy may not be obligatory for nonmyasthenic patients with clinical stages I to II thymoma. Larger studies and longer follow-up are awaited.

Lymph node dissection — A standardized lymph node mapping system was established by the ITMIG/International Association for the Study of Lung Cancer (IASLC) Thymic Epithelial Tumors Staging Project in 2014 as part of the 8^th edition of the TNM Classification of Malignant Tumors [68]. In this system, N1 nodes were classified as anterior region nodes, and N2 nodes were classified as deep region nodes.

●Anterior thymic region – The anterior thymic region (N1) nodes are located in the space around the thymus anterior to the pericardium and great vessels, below the hyoid bone, above the diaphragm, between the mediastinal pleural, and posterior to the sternum (table 4). These boundaries are the same as extended thymectomy; thus, the N1 nodes will be included in the resection.

●Deep thymic region – The deep thymic region (N2) nodes include the lower jugular, supraclavicular, internal mammary, upper paratracheal, lower paratracheal, subaortic/aortopulmonary window, and hilar nodes. The node group boundaries are defined in the table (table 5).

For thymomas with no invasion of mediastinal structures, only anterior region (N1) nodes are required as included in extended thymectomy. For thymomas with invasion of mediastinal structures, systemic sampling of deep lymph nodes (N2) is recommended. For thymic carcinoma treated with curative intent, systematic resection of both N1 and N2 nodes is recommended.

With regard to thymic carcinoma, one study found that a minimum of 10 lymph nodes appeared to correlate with better patient survival [69]. This study also supports the recommendation for dissection of nodes from both N1 and N2 nodal regions, especially in the presence of adjacent tumor invasion.

Handling the phrenic nerves — Every attempt should be made to preserve the phrenic nerves.

●Iatrogenic phrenic nerve injury is a concerning complication that leads to hemidiaphragm paralysis, which can be seen on postoperative chest radiograph. Avoidance of injury can be aided by:

•Staying at least 1 cm away during pleural dissection.

•Using sharp dissection when near the nerve.

•Avoiding unnecessary traction on the nerve during dissection.

•Leaving a small remnant of fatty tissue on the phrenic pedicles.

●For unilateral phrenic nerve involvement of the tumor:

•If preoperative testing showed ipsilateral hemidiaphragm paresis, the nonfunctional nerve can be resected.

•If one nerve is involved and the patient has relatively good pulmonary function, the invaded nerve should be resected en bloc with the specimen.

•Ipsilateral diaphragm plication is an option at the time of phrenic nerve sacrifice, although watchful waiting for symptoms and offering it at a later date is also appropriate [70]. (See "Treatment of bilateral diaphragmatic paralysis in adults".)

•For patients with myasthenia gravis, resection of even one phrenic nerve can lead to significant respiratory problems and should be avoided.

●When both nerves are involved, management involves multidisciplinary discussion between the surgeon and radiation oncologist. One nerve can be resected, but the other nerve should be preserved, if possible, even if this means leaving small-volume (ideally R1) tumor behind, which can be addressed postoperatively with adjuvant radiotherapy. Alternatively, both nerves may be retained, with dissection of the tumor away from each nerve. For either approach, postoperative radiation therapy (RT) to the area of residual disease is performed, though the field of treatment is larger if both nerves are retained. Importantly, bilateral phrenic nerve resection should never be performed, because it will result in respiratory compromise, morbidity, and mortality. If the patient has myasthenia gravis, resection of even one phrenic nerve may lead to significant respiratory problems and should be avoided. (See "Clinical presentation and management of thymoma and thymic carcinoma", section on 'Postoperative radiation therapy'.)

●While data are limited, several case reports and case series report the feasibility and outcomes of immediate phrenic nerve reconstruction including direct anastomosis, or the use of sural nerve or intercostal nerve transfer [71-73]. (See "Surgical treatment of phrenic nerve injury".)

Techniques

Transsternal thymectomy — Radical transsternal thymectomy is the standard approach for thymectomy and provides excellent exposure of the anterior mediastinum and thymus. It is performed via a standard median sternotomy. The patient is intubated with a double-lumen endotracheal tube with standard monitoring lines, including an arterial line, and positioned supine with arms tucked and a shoulder roll [74].

Median sternotomy is performed through a midline chest incision from 2 cm below the sternal notch to the xiphoid process (figure 4). The subcutaneous tissue is divided, making certain to stay midline down to the pectoralis fascia. The midline is determined by a combination of division of the decussation of the pectoralis muscle fibers and palpation of the intercostal spaces (sometimes with assistance of a hemostat for larger anterior chests) and marked. The sternal notch is cleared of soft tissue and the interclavicular ligament, and the retrosternal space is developed bluntly. The xiphoid and inferior retrosternal space is developed in a similar manner. The xiphoid may be resected, if necessary. Division of the sternum is performed with a sternal saw, and standard techniques for controlling bleeding from the sternum are applied. Once the sternotomy is completed, a sternal retractor is placed.

The dissection is usually begun on the right side to identify the superior vena cava and subsequently the innominate vein. The right pleural cavity is entered and opened widely. The right lung is packed away, and the pleural cavity is inspected for metastatic disease. The right phrenic nerve, which courses medially (figure 3), and superior vena cava are identified. The mediastinal parietal pleural is divided 1 cm anterior to the phrenic nerve and extended superiorly and inferiorly. The incised pleura is elevated, and all tissue is swept anteromedially off the pericardium. Tissue deep to the phrenic nerve should be included in this specimen, taking care to identify small branches from the phrenic vessels and dividing with ultrasonic shears, clips, or by packing, but not by using electrocautery. The right lung is reinflated and the left-sided dissection is carried out in a similar manner. The left phrenic nerve is located more posteriorly due to the position of the heart (figure 2).

With the gland freed inferiorly, it can now be retracted cephalad and separated from the pericardium by sharp dissection. Small vessels from the internal mammary vessels can be divided with ultrasonic shears. As the dissection continues cephalad, all fatty tissue between the superior vena cava and aorta should be included in the specimen. The innominate vein is identified, and branches to the thymus are divided. Fatty tissue deep to the innominate vein is also resected en bloc. The aorticopulmonary window should also be dissected of fatty tissue; however, care must be taken to avoid the recurrent laryngeal nerve.

Dissection is continued cephalad to the superior horns, and traction is applied inferiorly to identify, ligate, and divide the thyrothymic ligaments. The resected specimen is removed en bloc and should include all fatty thymic tissue, thyrothymic ligaments, and mediastinal pleura. The specimen should be marked and oriented for the pathologist.

Chest tubes are placed and secured, and the sternum is closed in standard fashion according to the preferences of the surgeon.

Transcervical thymectomy — Transcervical thymectomy, which can be performed with or without video assistance, was the first described surgical approach to thymectomy [75]; however, it has remained controversial and is not widely accepted due to lack of familiarity with the technique and general concerns for completeness of resection (ie, R0). Transcervical thymectomy is used in only a limited number of institutions with proponents advocating that surgical exposure is adequate (particularly with video assistance), the extent of resection is appropriate, pain is less, and avoidance of sternotomy and need for chest drainage (ie, thoracostomy tubes) is desirable [19,28,76]. (See 'Completeness of tumor resection' above.)

The most commonly used technique, the "extended" transcervical thymectomy (Cooper), which was introduced in 1988, is described here [77]. The patient is intubated with a single-lumen endotracheal tube and positioned supine with an inflatable bag behind the shoulders, donut under the head, and arms to the sides. The neck and chest are prepared for possible conversion to a sternotomy.

A transverse curvilinear incision is made 2 cm above the sternal notch between the sternocleidomastoid muscles (figure 5). The platysma is divided and an inferior subplatysmal plane is developed down to the sternal notch. The interclavicular (cleidocleido) ligament is divided. The superior flap is developed to the inferior thyroid gland. The strap muscles are separated at midline. If needed, the cervical incision can be extended inferiorly for partial or total (ie, extended) sternotomy.

The superior horns of the thymus can be found overlying the respective inferior thyroid veins. The left superior horn is isolated and cleared of areolar tissue, divided, and a silk ligature tied to the horn for retraction. This is repeated with the right superior horn. The superior horns come together at midline inferiorly anterior to the innominate vein near the level of the sternal notch.

The thymus is retracted anteriorly and dissected down to the innominate vein. Thymic veins draining into this vessel are isolated, ligated, and divided. A thymectomy Cooper retractor is then placed and secured for upward traction of the sternum (to nearly lift the patient from the table). The inflatable bag is deflated to increase retraction and visibility. The surgeon now sits at the head of the bed using a headlamp. The surgeon may also use a 5 mm 30-degree thoracoscope through this incision for assistance.

Dissection is continued behind the thymus anterior to the innominate vein and inferiorly over the pericardium and aortic arch using sharp dissection. The inferior horns of the thymus are isolated and can be separated from the pleura by blunt dissection. Anterior to the thymus, arterial branches from the internal mammary arteries are ligated and divided. If the pericardium or pleura are densely adherent to the thymus, a portion of the pericardium or pleura can be taken with the specimen. Usually, the right inferior horn is dissected free, then the posterior thymus, then the left inferior horn. The thymus is then removed. Peripleural fat on both sides is to be excised and sent as separate specimens.

If the pleural space on either side was entered, these openings should be widened to allow evacuation of air. After hemostasis is assured, a red rubber catheter is placed in the anterior mediastinum out through the incision. Prior to closure of the platysma, the anesthesiologist performs a Valsalva to evacuate residual air. The red rubber catheter is then removed after placement of the platysmal suture, followed by skin closure. Alternatively, a drain can be placed into the mediastinum and brought out through a lateral neck stab incision.

Minimally invasive thymectomy — Several MIT approaches exist regarding port number, port placement, unilaterally, and bilaterally. The first thoracoscopic thymic resection (thymoma) used a transthoracic approach using five ports [78]. Three ports are typically used, though a subxiphoid approach uses a single port. Traditional VATS and robotic-assisted approaches are well described [79,80]. The basic principles of minimally invasive thoracic surgery are discussed separately. (See "Overview of minimally invasive thoracic surgery".)

Standard — The left-sided MITS approach to thymectomy uses three left standard ports with an option of an additional right thoracoscope port placement for an enhanced view of the right phrenic nerve. A right-sided approach (picture 1) can also be used with the ports placed in reverse.

Considerations on which side to approach from are based upon the location of pathology, patient anatomy, and surgeon preference. A left-sided approach provides excellent exposure of the larger amount of adipose tissue that is present in the left hemithorax compared with right mediastinum. On the other hand, a left-sided approach may be considered for patients with thymomatous or nonthymomatous myasthenia gravis since radical thymectomy with removal of pericardial, AP window, and mediastinal fat is thought to be important for disease control. Furthermore, the right phrenic nerve may be more easily seen from the left side, compared with the view of the left phrenic nerve from the right. Proponents of a right-sided approach note the larger working domain of the right compared with left hemithorax, given the position of the heart in the left chest.

Alternatively, some surgeons advocate a bilateral approach to maximally visualize each phrenic nerve and to facilitate resection of all perithymic adipose tissue in cases of myasthenia gravis. For bilateral VATS or bilateral robotic-assisted thymectomy, special consideration should be made for positioning to avoid re-prepping and re-draping. One method is to place two pressure bags under the patient's back (on left and right), tucking the arms and inflating the pressure bag on the side to be operated on to elevate that side for the first portion of the operation. When that side is complete, the robot is undocked, the ipsilateral bag is deflated, and the contralateral side is inflated. Contralateral ports are placed, and the robot is docked 180 degrees to complete the second half of the procedure. Another method is to place two large gel rolls in a similar manner, loosely tucking the arms posteriorly and rotating the bed so that the operative side is elevated 30 degrees. In either setup, the chest should be prepped and draped widely.

The patient is intubated supine with a double-lumen endotracheal tube and rolled into a 30 degree decubitus position with a gel roll placed under the axilla. The neck, chest, and abdomen are prepped. Single-lung ventilation is initiated. For a left-sided approach, three 5 mm ports are placed along the left mammary crease with two in the fifth intercostal space and one in the third intercostal space. The first port is placed by direct cut down, and the remaining ports are placed under direct camera vision. The pericardium and heart must be protected during port placement to avoid injury. An intercostal nerve block is performed.

Carbon dioxide insufflation, which compresses lung tissue for retraction and aids in the dissection of areolar tissue planes, is initiated with a pressure limit of typically 8 mmHg. The pleural cavity is inspected, and the lung is retracted posteriorly to identify the thymus, phrenic nerve, and mammary vessels.

The anterior and posterior planes of dissection are established by:

●Dividing the mediastinal pleura 1 cm medial and parallel to the phrenic nerve with thoracoscopic scissors. Energy devices, specifically unipolar electrocautery, should be used sparingly near the phrenic nerve.

●Dividing the parietal pleura just medial to the mammary vessels with unipolar energy.

Posteriorly, the pericardial fat, mediastinal pleura, and thymus are carefully dissected off the pericardium, starting inferiorly at the pericardial fat along the diaphragm anteriorly. This fat is dissected superiorly to its intersection with the thymus gland, which is teased off the pericardium. The dissection is continued along the anterior aspect of the thymus off the chest wall. Feeding vessels from the mammary vessels can be divided with clips or electrocautery. A lateral-to-medial dissection is carried as far as can be done safely. Next, the left thymic horn is dissected and divided at the thyrothymic ligament. The innominate vein is identified during the superior dissection, and thymic veins draining into the innominate vein are divided between clips or with an energy device.

At this point in the left thoracoscopic approach, a 5 mm port can be placed into the right pleural space to aid with exposure of the right phrenic nerve if it cannot be seen well from the left chest. Robotic video systems have a useful "TilePro" function that allows the operative surgeon to see both sides of the chest simultaneously on the screen. The lateral-to-medial dissection is continued across midline until the right pleura and phrenic nerve are identified posterior to the specimen and the right mammary vessels on the anterior aspect. The right pleura is opened 1 cm medial to the right phrenic nerve and medial to the right mammary vessels. The right superior horn is dissected and the thyrothymic ligament is divided, completing the resection.

The specimen is then placed in an endoscopic bag and removed with extension of the port incision to appropriate size. The specimen is marked for orientation and sent to pathology for permanent section. It is good practice for the surgeon to orient the pathologist to the specimen in person.

It is important to note:

●For thymectomies performed for MG, extended resections include the pericardial fat of both hemithoraces, aortopulmonary fat, and cervical fat, which should be resected with the thymus specimen since thymic tissue is identified in the adipose tissues of these regions and is believed to contribute to MG pathophysiology [81].

●For thymectomies performed for thymoma, a "no-touch" technique of the thymoma itself should be used to minimize disruption of the tumor capsule, which can result in pleural recurrence. In these cases, the surgeon must carefully evaluate surrounding structures for evidence of invasion including the pericardium, lung, and innominate vein, each of which can be resected. However, such radical resections should only be resected using a minimally invasive approach by surgeons with sufficient experience in these extended resections. There should be a low threshold for conversion to an open procedure to obtain an R0 resection, which is imperative for minimizing local recurrence.

The thorax is checked for hemostasis. Three chest tubes are placed in the left pleural space, right pleural space, and anterior mediastinum. The lungs are reinflated under direct camera vision. All port sites are closed in layers.

Subxiphoid thymectomy — The author prefers a robotic subxiphoid approach as described in the following paragraphs. An alternative is a uniportal subxiphoid approach.

The patient is positioned supine with the upper extremities adducted and a small roll placed under the lumbar spine to slightly increase the angle up the epigastric area to the retrosternal space. The patient is intubated with a single-lumen endotracheal tube (double lumen may be used, but typically not necessary) and prepped from umbilicus to neck, and lateral to the bed. This position/prep allows easy transition to sternotomy in rare cases requiring conversion. A sternal saw should be available and confirmed working.

The subxiphoid dissection is the main reason surgeons tend not to perform this approach from a comfort level, but the dissection is actually very similar to the dissection used during a standard median sternotomy. A 3 cm longitudinal incision placed 1 cm caudad to the xiphoid process is made and dissection is carried down to the abdominal fascia. The linea alba is identified and divided, making sure not to violate the peritoneum. A substernal tunnel is developed with finger dissection and a gel multiport (two 8 mm robotic ports) is placed. The space is insufflated to 8 mmHg.

Using a uniportal technique, the thymus is dissected away from the posterior surface of the sternum using a bipolar Maryland dissector (eg, Ligasure), creating more space along the way. The dissection is carried laterally on the right to identify the internal mammary vessels. The mediastinal pleura is opened medial to the right internal mammary vessels, allowing entry into the right pleural space and extended cephalad and caudad. These steps are repeated on the left.

Two 8mm robotic ports are placed under direct vision in the 6th or 7th intercostal space at the midclavicular/anterior axillary line. Intercostal nerve blocks are performed bilaterally from ribs 4 to 8 using bupivacaine with epinephrine. The robot is docked with three arms: Cadiere forceps/long bipolar vessel sealer; 30-degree robotic camera; and long bipolar vessel sealer/Cadiere forceps. The retrosternal dissection is continued to the neck. The anterior mediastinal pleura is opened bilaterally in the cephalad direction to the takeoff of the internal mammary vessels.

The inferior horns are sequentially identified and dissected from the diaphragm and pericardium. If required, a more cephalad port may be placed on either side, and the camera can be moved for better visualization/dissection. This is often not necessary but may be helpful in larger patients with extensive mediastinal tissue. The inferior midthymus is then dissected from the anterior pericardium. The right phrenic nerve is identified and the mediastinal pleura 1 cm anterior to the nerve is divided and extended cephalad to the anterior dissection. These steps are repeated on the left side.

The thymus is carefully retracted cephalad, and the pericardium is evaluated for invasion. The thymus/mass is then swept or dissected from the pericardium and carried further cephalad to expose the innominate vein. The lateral right and left thymic dissection are continued, making sure to identify and protect the phrenic nerves, superior vena cava, and innominate vein. The thymus is retracted caudad allowing dissection of the superior right and left thymic horns from the neck. Any thymic veins draining into the innominate vein are divided with the bipolar sealing device or clipped. The remaining connective tissue is divided, separating the thymus/mass from the chest. The camera is moved to the right-hand port and a large endoscopic retrieval bag is placed through the multiport for specimen retrieval. The extended thymectomy specimen is examined on the back table, oriented, and sent to pathology for permanent section.

After hemostasis is confirmed, the robotic instruments and camera are removed and the robotic is undocked. A 24 Fr Blake drain is placed through the left-hand incision (ie, patient's right) into the right pleural space, across the anterior mediastinum, and into the left pleural space and secured with a silk anchor stitch in the skin. The lungs are inflated and the chest ports are closed in layers. The midline fascia is closed with absorbable, braided, polyglactin O-suture (eg, Vicryl). The Blake tube is attached to a closed suction device with -20 mmHg suction. If there is no air lead, the tube is removed on postoperative day one.

Lymph node dissection — As discussed above, the standard of care for most thymic resections is an extended thymectomy, and by definition, this includes N1 lymph nodes (anterior thymic region nodes) (table 4). For thymomas with invasion to adjacent structures, and resectable thymic carcinomas, we recommend dissection of the deep thymic region N2 lymph nodes (table 5).

POSTOPERATIVE CARE AND FOLLOW-UP — The expectation is that most patients will be extubated in the operating room. Thus, most patients will not need to go to the intensive care unit (ICU); however, the threshold for ICU admission should be low if there is any possibility for myasthenic crisis. (See "Anesthesia for the patient with myasthenia gravis", section on 'Prediction of postoperative myasthenic crisis'.)

A postoperative chest radiograph is obtained in the recovery unit to evaluate lung expansion, chest tube or drain positioning, diaphragmatic elevation, and for the presence of any pulmonary edema.

For transsternal thymectomy, the patient may need fluid administration due to third spacing. Daily chest radiographs should be obtained. Sternal precautions should be maintained for two months. This includes avoiding heavy lifting and extremes of shoulder movement (eg, as in tennis, baseball, and golf) for six to eight weeks after surgery to allow for complete healing of the breastbone (sternum).

Pain can be controlled with patient-controlled anesthesia and transitioned to oral medications once the patient tolerates a diet. In general, less invasive approaches are expected to have less postoperative pain and lower pain medication requirements. (See "Approach to the management of acute pain in adults".)

Chest tubes should be removed as soon as they are no longer needed: once the output is low, the quality is not sanguinous, and there is no air leak, typically on postoperative day 1 following minimally invasive surgery. (See "Thoracostomy tubes and catheters: Indications and tube selection in adults and children".)

For patients with myasthenia gravis, in the immediate postoperative period, the patient's respiratory status and ventilatory support are of utmost importance. With careful preoperative preparation, respiratory problems can be minimized. Inpatient consultation by the neurology service for all patients with myasthenia gravis is often helpful. Respiratory status is assessed based on the patient's clinical appearance, and any sign of increasing respiratory or bulbar muscle weakness should prompt further evaluation including intensive care unit admission, neurology consultation, frequent monitoring of respiratory strength, and if necessary, elective intubation. A maximal inspiratory pressure (MIP), or negative inspiratory force (NIF), can be measured at bedside, and a value below 1/3 of normal (0 to -30 cmH2O) indicates severe respiratory muscle weakness. (See 'Evaluation for myasthenia gravis' above and "Myasthenic crisis".)

Follow-up — All patients should be followed up in two weeks in the surgical clinic to evaluate the wound and to undergo chest radiography to evaluate for pneumothorax, pleural effusions, and diaphragm dysfunction. The final results of histopathologic examination of the resection specimen are reviewed with the patient along with implications for further treatment. Histopathology is required for definitive staging and determines whether postoperative therapy is recommended.

Patients with myasthenia gravis should have close follow-up with their neurologist, who will manage their need for continued myasthenia medications, including tapering those medications.

Following tumor resection, surveillance is performed at regular intervals. (See "Clinical presentation and management of thymoma and thymic carcinoma", section on 'Surveillance after treatment' and "Thymic neuroendocrine (carcinoid) tumors", section on 'Post-treatment surveillance'.)

COMPLICATIONS — The main complications specific to thymectomy are pulmonary complications, primarily related to myasthenia gravis, and inadvertent nerve injury. Surgical site infection and mediastinitis are uncommon but potentially serious complications. Long-term patients may have complications related to altered immune function. These complications are reviewed briefly below.

Cardiac complications can also occur and include dysrhythmias, such as atrial fibrillation. (See "Postoperative complications among patients undergoing cardiac surgery", section on 'Cardiac dysfunction'.)

Pulmonary complications — Pulmonary complications, including respiratory failure and prolonged intubation, are more commonly associated with patients with myasthenia gravis. Otherwise, pulmonary complications can include pleural effusion, pneumonia, atelectasis, pneumothorax, acute lung injury, and decreased thoracic compliance. Perioperative management of myasthenia gravis, including myasthenic crisis, is discussed separately. (See "Anesthesia for the patient with myasthenia gravis", section on 'Postoperative considerations for patients with myasthenia gravis'.)

In a retrospective review from the Japanese Association of Research on the Thymus (JART) of 280 propensity matched patients (2835 original cohort) who underwent thymectomy for thymoma between 1991 and 2010, myasthenic crisis occurred in 4.4 percent of patients with myasthenia gravis [82]. There was no significant difference in the incidence of postoperative myasthenic crisis comparing video-assisted thoracoscopic surgery (VATS) and sternotomy (4.4 versus 4.3 percent). [83]

Nerve injury — Nerves at risk for injury during thymectomy include the phrenic nerves and recurrent laryngeal nerves [84-88].

Injury to the phrenic nerve can be avoided by minimizing dissection, traction, and use of electrocautery near the nerve. True comparisons of the incidence of phrenic nerve injury during thymectomy are limited by the lack of trials. The incidence of recurrent laryngeal nerve injury is even further limited. In observational studies:

●For transsternal thymectomy, the incidence of phrenic nerve injury is reported to be less than 1 percent [89].

●In a Mayo Clinic study, among patients who underwent minimally invasive VATS thymectomy, 3/45 (7 percent) had phrenic nerve injury, while none in the robotic-assisted group had such an injury [90].

If phrenic nerve injury occurs and does not improve with time (algorithm 1), options include diaphragm plication or phrenic nerve reconstruction in experienced hands. (See "Surgical treatment of phrenic nerve injury".)

Left recurrent laryngeal injury, which can lead to vocal cord paralysis, can occur with dissection of the aorticopulmonary window. The right recurrent laryngeal nerve courses around the right subclavian artery, which is above the innominate vein and outside of the margin for thymectomy.

Surgical site infection and mediastinitis — Surgical site infection (SSI) is overall uncommon but has been reported. In a review of 125 transsternal thymectomies, SSI and mediastinitis occurred in 2.4 and 1.6 percent of patients, respectively [91]. Mediastinitis is more likely with a sternotomy approach but has also been reported following the transcervical approach [92].

Minimization of steroids is traditionally recommended to minimize impaired wound healing, but no study has conclusively shown that high preoperative steroid use is associated with high wound infection rate, dehiscence, or mediastinitis following thymectomy. In a retrospective review that compared 70 patients with myasthenia gravis undergoing thymectomy treated with high-dose prednisolone therapy preoperatively and 60 patients who underwent thymectomy with no preoperative prednisolone, wound dehiscence occurred in significantly more patients in the steroid group (4/70 [5.7 percent] versus 1/60 [1.7 percent]) [93]. Counterintuitively, wound infection occurred only in the nonsteroid group (4.9 versus 0 percent). It is unclear if these results are meaningful given the small number of events.

The clinical features and diagnosis of surgical site infection, sternal infection, and mediastinitis are presented separately. (See "Overview of the evaluation and management of surgical site infection" and "Surgical management of sternal wound complications".)

Potential complications related to altered immune function — The question of the effect of thymectomy on the immune system has been raised and is intriguing. The thymus is important to the development of immune function in infants and children; however, since the thymus naturally involutes with age, the role of the thymus in adults is debated. A database review of the Mass General Brigham Research Patient Data Registry evaluated long-term of thymectomy. All-cause mortality (8.1 versus 2.8 percent, relative risk [RR] 2.9, 95% CI 1.7-4.8) and the risk of cancer (7.4 versus 3.7 percent, RR 2.0, 95% CI, 1.3-3.2) were increased in patients who underwent thymectomy for a variety of indications and approaches compared with a matched control population (ie, cardiac surgery without thymectomy) [94]. The risk of autoimmune disease was also increased for thymectomy (12.3 versus 7.9 percent, RR 1.5, 95% CI, 1.02-2.2) when patients with preoperative infection, cancer, or autoimmune disease were excluded from the analysis. The authors made no conclusions regarding causality and noted that further studies are needed. Nevertheless, it may be advisable to avoid incidental removal of the thymus to potentially minimize long-term health consequences.

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Myasthenia gravis" and "Society guideline links: Thymomas and thymic carcinomas".)

SUMMARY AND RECOMMENDATIONS

●Thymectomy – Thymectomy is indicated for the treatment of patients with thymoma, thymic carcinoma, thymic neuroendocrine tumor, myasthenia gravis with thymoma, and nonthymomatous myasthenia gravis. Preoperative imaging evaluation is useful to determine whether the tumor is resectable and the possible benefit for neoadjuvant treatment. (See 'Introduction' above and 'Confirm resectability and tumor staging' above.)

●Multidisciplinary care – Perioperative management of patients with myasthenia gravis requires a multidisciplinary approach involving the surgeon, anesthesiologist, neurologist, intensivist, respiratory therapist, and pulmonologist. (See 'Anesthesia and perioperative care' above and 'Evaluation for myasthenia gravis' above.)

●Principles of resection – The general principles of thymectomy include the following (see 'Incisions and surgical approach' above and 'Extent of resection' above):

•Extent of resection – Total (ie, extended) thymectomy involves complete removal of the gland, including resection of all four thymic lobes. Since it is not possible to differentiate the thymus from adipose tissue, resection requires complete removal of all tissue anterior to the pericardium from the innominate vessels to the diaphragm, and from the left to the right phrenic nerve.

•Phrenic nerve preservation – Preservation of the phrenic nerves. If the tumor involves one phrenic nerve, it can be sacrificed; however, if both nerves are involved, every attempt should be made to preserve one. For patients with myasthenia gravis, resection of even one phrenic nerve can lead to significant respiratory problems and should be avoided.

•Need for en bloc removal – If the pericardium/lungs/periosteum or innominate vein is involved, tumor must be removed en bloc with the involved structure(s).

•Need for lymphadenectomy – Thymoma without invasion requires N1 anterior region lymph nodes to be removed. These nodes are included in the extended thymectomy. Thymomas that invade adjacent structures and thymic carcinomas require N2 deep region lymph node sampling.

●Surgical approach – Surgical approaches to thymectomy use either a median sternotomy (transsternal), multiple small incisions (chest wall, subxiphoid) for port placement (video-assisted thoracoscopic or robotic-assisted thoracoscopic surgery), or a low horizontal neck incision (transcervical; with or without video assistance). Conversion to thoracotomy or sternotomy may be required to control bleeding with minimally invasive approaches. (See 'Procedure' above.)

•Open thymectomy - Open thymectomy using a transsternal technique is the standard technique and provides the widest exposure; however, it is also the most invasive and painful. (See 'Transsternal thymectomy' above.)

•Minimally invasive thymectomy - Minimally invasive thymectomy (MIT; video-assisted, robotic-assisted) is a popular technique and is associated with shorter hospitalization, less blood loss, less postoperative pulmonary dysfunction, and less pain. (See 'Minimally invasive thymectomy' above.)

-Complete resection of the thymus gland can be achieved by standard video-assisted thoracoscopic surgery (VATS), but a bilateral approach may be needed to see both phrenic nerves.

-A subxiphoid approach offers the advantages of a minimally invasive approach, including a view of the phrenic nerves bilaterally and reduced pain from intercostal incisions.

•Transcervical – A transcervical approach with video assistance is performed at select centers. The benefit is faster recovery and less pain, but whether the view is optimal, and the completeness of resection, is debated. (See 'Transcervical thymectomy' above.)

●Complications – The main complications specific to thymectomy are pulmonary complications, primarily related to myasthenia gravis, and inadvertent nerve injury. Surgical site infection and mediastinitis can also occur but are rare. Injury to the phrenic nerve can be avoided by minimizing dissection, traction, and use of electrocautery near the nerve. Left recurrent laryngeal nerve injury is avoided by taking care during dissection of the aorticopulmonary window. (See 'Complications' above.)

ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Bryan M Burt, MD, who contributed to earlier versions of this topic review.