Outcomes of extended surgical resections for locally advanced thymic malignancies: a narrative review.

Background and Objective: Thymic malignancies represent the most common anterior mediastinal neoplasms, as well as rare and challenging tumors. Surgery is the cornerstone in the treatment of thymic malignancies, although a multidisciplinary approach is mandatory, for both, locally advanced or metastatic disease. In our narrative review, we explored the recent literature to investigate clinical and radiological assessment, multimodality approach and outcomes of locally advanced thymic tumors. More than one-third of patients affected by an anterior mediastinal mass are asymptomatic at diagnosis. In case of locally advanced thymoma, symptoms are related to compression or invasion of adjacent structures, such as the superior vena cava (SVC), innominate veins and pericardium. Paraneoplastic syndromes, such as myasthenia gravis (MG), are related to release of antibodies, hormones and cytokines. Methods: Diagnostic methods must be chosen accurately to avoid unnecessary surgical resections, to define the best strategy of care, and to plan the surgical strategy. Therefore, each case must be evaluated in a multidisciplinary context, where surgery plays an essential role. Key Content and Findings: In this narrative review, we describe indications and surgical techniques for the treatment of locally advanced thymoma; focusing on oncological outcomes after different approaches. Conclusions: In conclusion, aggressive surgery is always indicated, when possible, and when a complete resection can be planned, yet, the multidisciplinary approach is mandatory, in case of both locally or metastatic advanced disease.

[Analysis of Influencing Factors for Postoperative Venous Thromboembolism 
of Thymic Malignancies].

BACKGROUND: The previous study has indicated that the incidence of venous thromboembolism (VTE) after thoracic surgery is high. The purpose of this study was to analyze the incidence and risk factors of postoperative VTE in thymic malignancy patients. METHODS: This was a single-center study. Patients undergoing resection for thymic malignancy between December 2017 and February 2021 in Department of Thoracic Surgery, Beijing Tongren Hospital Affiliated to Capital Medical University were enrolled in this study. In addition to the routine examination, all patients were screened for deep venous thrombosis (DVT) by using noninvasive duplex lower extremity ultrasound before and after surgery. Patients did not receive any prophylactic anticoagulant therapy before and after surgery. All patients received modified caprini risk assessment. According to whether VTE occurred after operation, patients were divided into VTE group and control group. The clinical data of the two groups were compared. The occurrence time and possible high risk factors of VTE after operation were analyzed. RESULTS: A total of 169 patients with thymic malignant tumor were enrolled, including 94 males and 75 females, aging from 22 to 76 years. A total of 95 patients underwent thoracoscopic surgery and 74 patients underwent median sternotomy. The total incidence of VTE was 12.4%. The median time for diagnosis of VTE was 4 days (2 days-15 days) after operation. According to the modified caprini score, the incidence of VTE in low risk patients (Caprini score≤4 points), moderate risk patients (Caprini score 5 to 8 points) and high risk patients (Caprini score≥9 points) were 0% (0/7), 7.0% (8/115) and 27.7% (13/47), respectively (Z=1.670, P=0.008). Univariate analysis showed that there were significant differences between VTE group and control group in age, operation method, operation time, indwelling central venous catheter, postoperative bed rest time more than 72 hours (P<0.05). Multivariate analysis showed that over 60 years old, operation method and operation time were independent risk factors for VTE after resection for thymic malignancies. CONCLUSIONS: Over 60 years old, operation method and operation time are independent risk factors for VTE. Modified caprini assessment can effectively screen high-risk patients.

A rare initial presentation of a thymic neuroendocrine tumor as Cushing's syndrome.

While evaluating the cause of Cushing's syndrome, biochemical confirmation should be sought first as imaging studies might misdirect the diagnosis toward the wrong problem. One of the rare secondary causes that should be kept in mind while evaluating Cushing's syndrome is the thymic neuroendocrine tumor.

Long-term, disease-specific outcomes of thymic malignancies presenting with de novo pleural metastasis.

OBJECTIVE: Treatment of patients with thymic malignancies metastatic to the pleura or pericardium is challenging, and benefits of aggressive treatment are unclear. We sought to characterize the long-term outcomes in this population. METHODS: We retrospectively identified patients who underwent resection for de novo thymic malignancies metastatic to the pleura between May 1997 and December 2017. Patients with pleural recurrence after prior thymectomy were excluded. Patient demographics, perioperative treatments, pathologic findings, and postoperative outcomes were collected. Descriptive statistics and Kaplan-Meier analyses were performed. RESULTS: Seventy-two patients were included (median age, 51 years [range 25-80]; 36/72 women [50%]). Pathologic diagnosis was thymoma in 57 patients (79%) and thymic carcinoma in 15 patients (21%). Most patients (67/72; 93%) received chemotherapy, radiation, or both. Forty-eight patients underwent thymectomy with pleurectomy, 7 patients underwent extrapleural pneumonectomy, 10 patients underwent thymectomy alone, and 7 patients were unresectable. Macroscopic complete resection was achieved in 52 patients (73%). Five-, 10-, and 15-year overall survivals were 73%, 51%, and 18%, respectively, and median overall survival was 11 years (median follow-up, 5.9 years). Forty-six patients (64%) had disease progression (median time to progression, 2.2 years). Repeat episodes of progression and treatment were common (median, 3 episodes/patient). The longest disease-free interval was 12.4 years. Thirteen patients (18%) remain disease-free; 7 patients (10%) were disease-free for more than 5 years. The longest ongoing survival without progression or reintervention is 9.9 years. CONCLUSIONS: Prolonged survival and, in some cases, cure can be achieved in patients with thymic malignancies metastatic to the pleura or pericardium. Aggressive multimodality therapy may be appropriate for select patients.

Impact of Lymph Node Dissection on Thymic Malignancies: Multi-Institutional Propensity Score Matched Analysis.

INTRODUCTION: Surgical resection is a standard treatment for thymic malignancies. However, prognostic significance of nodal metastases and lymph node dissection remains unclear. The aim of this study is to determine prognostic significance of nodal metastases and the role of lymph node dissection (LND) in thymic malignancies. METHODS: Between 2000 and 2013, 1597 patients who underwent thymectomy due to thymic malignancy were included. Predictive factors for nodal metastasis and prognostic significance of LND were evaluated. Patients were divided into two groups: (1) LND+ group, with intentional LND (446 patients, 27.9%); and (2) LND- group, without intentional LND (1151 patients, 72.1%). Propensity score matching was performed between the two groups. RESULTS: Lymph node metastasis was identified in 20 (6.7%) of 298 patients with thymoma and 47 (31.7%) of 148 patients with thymic carcinoma. In multivariable analysis, thymic carcinoma (hazard ratio: 19.2, p < 0.001) and tumor size (hazard ratio: 1.09, p = 0.02) were significant predictive factors for lymph node metastasis. The 10-year freedom from recurrence rate of pN1 and pN2 was significantly worse than that of pN0 (p < 0.001). LND did not increase operative mortality or complication. There was no significant difference in 10-year freedom from recurrence rate between LND+ and LND- groups (82.4% versus 80.9%, p = 0.46 in thymoma; 45.7% versus 44.0%, p = 0.42 in thymic carcinoma). CONCLUSIONS: Lymph node metastasis was a significant prognostic factor in thymic malignancies. Although LND did not improve long-term outcomes in thymic malignancies, LND played a role in accurate staging, and improved prediction of prognosis.

Minimally invasive surgery in thymic malignances: the new standard of care.

Surgery is the most important therapy for thymic malignancies. The last decade has seen increasing adoption of minimally invasive thymectomy (MIT) for thymic tumors. MIT for early stage diseases has been shown to yield similar oncological results while being helpful in minimizing surgical trauma, improving postoperative recovery, and reducing incisional pain. Similar surgical and oncological principles should be observed in both minimally invasive and open procedures so as to ensure radical resection and accurate staging of the tumor.

Analysis of Influencing Factors for Postoperative Venous Thromboembolism of Thymic Malignancies / 中国肺癌杂志

BACKGROUND@#The previous study has indicated that the incidence of venous thromboembolism (VTE) after thoracic surgery is high. The purpose of this study was to analyze the incidence and risk factors of postoperative VTE in thymic malignancy patients.@*METHODS@#This was a single-center study. Patients undergoing resection for thymic malignancy between December 2017 and February 2021 in Department of Thoracic Surgery, Beijing Tongren Hospital Affiliated to Capital Medical University were enrolled in this study. In addition to the routine examination, all patients were screened for deep venous thrombosis (DVT) by using noninvasive duplex lower extremity ultrasound before and after surgery. Patients did not receive any prophylactic anticoagulant therapy before and after surgery. All patients received modified caprini risk assessment. According to whether VTE occurred after operation, patients were divided into VTE group and control group. The clinical data of the two groups were compared. The occurrence time and possible high risk factors of VTE after operation were analyzed.@*RESULTS@#A total of 169 patients with thymic malignant tumor were enrolled, including 94 males and 75 females, aging from 22 to 76 years. A total of 95 patients underwent thoracoscopic surgery and 74 patients underwent median sternotomy. The total incidence of VTE was 12.4%. The median time for diagnosis of VTE was 4 days (2 days-15 days) after operation. According to the modified caprini score, the incidence of VTE in low risk patients (Caprini score≤4 points), moderate risk patients (Caprini score 5 to 8 points) and high risk patients (Caprini score≥9 points) were 0% (0/7), 7.0% (8/115) and 27.7% (13/47), respectively (Z=1.670, P=0.008). Univariate analysis showed that there were significant differences between VTE group and control group in age, operation method, operation time, indwelling central venous catheter, postoperative bed rest time more than 72 hours (P<0.05). Multivariate analysis showed that over 60 years old, operation method and operation time were independent risk factors for VTE after resection for thymic malignancies.@*CONCLUSIONS@#Over 60 years old, operation method and operation time are independent risk factors for VTE. Modified caprini assessment can effectively screen high-risk patients.

Perioperative outcomes and long-term survival in clinically early-stage thymic malignancies: video-assisted thoracoscopic thymectomy versus open approaches.

BACKGROUND: Video-assisted thoracoscopic surgery (VATS) theoretically offers advantages over open thymectomy for clinically early-stage (Masaoka-Koga stage I and II) thymic malignancies. However, long-term outcomes have not been well studied. We compared the postoperative outcomes and survival from a cohort study based on the database of the Chinese Alliance for Research in Thymomas (ChART). METHODS: Between 1994 and 2012, data of 1,117 patients having surgery for clinically early-stage (Masaoka-Koga stage I and II) tumors were enrolled for the study. Among them, 241 cases underwent VATS thymectomy (VATS group), while 876 cases underwent open thymectomy (Open group). Univariate analyses were used to compare the clinical character and perioperative outcomes between the two groups. And multivariate analysis was performed to determine the independent predictive factors for long-term survival. RESULTS: Compared with the Open group, the VATS group had higher percentage of total thymectomy (80.5% vs. 73.9%, P=0.028), resection rate (98.8% vs. 88.7%, P=0.000) and less recurrence (2.9% vs. 16.0%, P=0.000). Five-year overall survival was 92% after VATS and 92% after open thymectomy, with no significant difference between the two groups (P=0.15). However, 5-year disease free survival were 92% in VATS group and 83% in Open group (P=0.011). Cox proportional hazards model revealed that WHO classification, Masaoka-Koga stage and adjuvant therapy were independent predictive factors for overall survival, while surgical approach had no significant impact on long-term outcome. CONCLUSIONS: This study suggests that VATS thymectomy is an effective approach for clinically early-stage thymic malignancies. And it may offer better perioperative outcomes, as well as equal oncological survival.

Do thymic malignancies respond to target therapies?

A best evidence topic in cardiothoracic surgery was written according to a structured protocol. The question addressed was 'Do thymic malignancies respond to target therapies?' Altogether, 347 papers were found using the reported search, of which, in our opinion, 16 papers represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers were tabulated. We did not find any randomized controlled trials on target therapies for the thymic malignancies, due to the very small incidence of this tumour, and it seems unlikely that there will be any such trials in the foreseeable future. Three studies on target therapies showed that several cases of thymic malignancies were reported to have partial response (PR) to epidermal growth factor receptor tyrosine kinase inhibitors such as cetuximab and erlotinib, whereas, one study on erlotinib and another on gefitinib showed no activity. Proto-oncogene c-KIT (KIT) mutant thymic carcinomas were noted to benefit from target therapies, implying that systematic sequencing of KIT in thymic carcinoma tumours may be warranted for optimal patient selection. A study that investigated the efficacy of cixutumumab, a fully human IgG1 monoclonal antibody that binds to insulin-like growth factor 1 receptor, indicated that relapsed thymomas tended to respond, whereas thymic carcinoma did not. The antiangiogenesis agent belinostat had modest antitumour activity in heavily pretreated thymoma, but no response to thymic carcinoma was found. Several cases with metastatic thymic carcinoma showed that multitargeted kinase inhibitors, such as sunitinib and sorafenib, were effective. We concluded that, as the side-effects of the agents were tolerable in almost all reported cases, target therapies can be an option for patients with heavily pretreated thymoma.