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Se describe el caso clínico de un paciente de 54 años de edad, quien fue ingresado en el Hospital Docente Clínico-Quirúrgico Hermanos Ameijeiras de La Habana por presentar fiebre, hipotensión y diarrea, a lo que se añadió dificultad respiratoria complicada durante su estancia en la institución y requirió apoyo ventilatorio mecánico en la Unidad de Terapia Intensiva. Como hallazgo radiográfico se observó una sombra en el pulmón izquierdo que resultó ser un timoma; mientras que en el examen sanguíneo se comprobó hipogammaglobulinemia. Se decidió realizar timectomía convencional mediante esternotomía media, luego de lo cual evolucionó satisfactoriamente y se le dio el alta hospitalaria 10 días después.
The case report of a 54 years patient is described, who was admitted to Hermanos Ameijeiras Clinical-Surgical Teaching Hospital in Havana city due to fever, hypotension and diarrhea, to which complicated respiratory difficulty was added during his hospitalization and he required mechanical ventilator support in the Intensive Care Unit. As a radiographic finding, a shade in the left lung was observed that turned out to be a thymoma; while the blood test revealed hipogammaglobulinemia. It was decided to carry out conventional thymectomy by means of midline sternotomy, after which the patient had a favorable clinical course and was discharged from the hospital 10 days later.
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Resumen El síndrome de persona rígida es un cuadro neuro lógico infrecuente caracterizado por rigidez muscular de tronco y extremidades y espasmos musculares ga tillados por estímulos sensoriales o emocionales, que progresa hacia la postración. Cuenta con un mecanismo fisiopatogénico con base inmunológica, en el cual los autoanticuerpos, como el antiGAD65, cumplen un rol central. Asimismo, la detección de dichos anticuerpos corrobora el diagnóstico ante un paciente con cuadro clínico sugestivo. Un 4 a 6% de los casos tienen neoplasias subyacentes. El tratamiento se basa en el manejo sintomático, inmunomodulador y de la enfermedad de base en los casos paraneoplásicos. Reportamos un caso de síndrome de persona rígida clásico asociado a timoma y describimos las características principales de esta entidad.
Abstract Stiff-person syndrome is a rare neurological condi tion characterized by muscular rigidity of the trunk and extremities and muscle spasms triggered by sensory or emotional stimuli, which progresses towards prostra tion. It has a pathophysiogenic mechanism with an immunological basis, in which autoantibodies, such as antiGAD65, play a central role. Likewise, the detec tion of these antibodies corroborates the diagnosis in a patient with a suggestive clinical picture. Four to 6% of cases have underlying neoplasms. Treatment is based on symptomatic, immunomodulatory, and underlying disease management in paraneoplastic cases. We re port a case of classic stiff person syndrome associated with thymoma and review the main characteristics of this entity.
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RESUMEN El timoma cervical ectópico es una patología poco frecuente, motivo por el cual su diagnóstico suele ser dificultoso. Debe ser tenido en cuenta como diagnóstico diferencial en pacientes con masas cervicales laterales, sobre todo aquellas que se ubican cerca de la glándula tiroides. El tratamiento consiste en la resección quirúrgica completa. Son tumores de crecimiento lento, la mayoría de ellos histológicamente benignos. En el caso aquí presentado, por su tamaño y ubicación, fue necesario separarlo de los grandes vasos y estructuras nerviosas cercanas, lo que hizo más compleja la cirugía.
ABSTRACT Ectopic cervical thymoma is a rare entity; therefore, its diagnosis is often difficult. It should be considered as a differential diagnosis in patients with lateral cervical masses, especially those close to the thyroid gland. Surgical treatment is indicated with complete excision of the lesion. Cervical thymomas are slow-growing tumors, usually benign. In this case report, due to tumor size and location, it was necessary to separate it from the large vessels and adjacent nerve structures, resulting in a more complex procedure.
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Recurrent pericardial effusion is always complicated for the primary care physician to diagnose, and it often goes undiagnosed. Thymoma is rare cancer, but it is the most common tumor in the anterior mediastinum. It can present in a variety of ways; it can be asymptomatic for an extended period of time and only rarely as pericardial effusion. A 68‑year‑old male presented to us with two episodes of pericardial effusion in the previous 2 years and was later diagnosed with thymoma.
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Paraneoplastic pemphigus (PNP) is a rare and life-threatening autoimmune blistering disease characterized by severe mucosal erosions and polymorphous cutaneous eruptions associated with lymphoproliferative neoplasmas. Castleman's disease, non-Hodgkin's lymphoma, thymoma, follicular dendritic cell sarcoma and chronic lymphocytic leukemia are the commonly associated neoplasmas in PNP, whereas malignant thymoma is rare. The prognosis of PNP is poor due to severe infections during immunosuppressive treatment, underlying malignancies and bronchiolitis obliterans mediated by autoimmunity. A 58-year-old woman who experienced recurrent oral erosive ulcer for 3 years, systemic erythema for 10 months, and dyspnea for 3 months was diagnosed with PNP with malignant thymoma and obliterated bronchiolitis by clinical, radiological, histopathological, and immunological examinations. She died of respiratory failure 3 weeks after resection of the malignant thymoma.
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Patients with thymoma without preoperative myasthenia gravis may develop symptoms of myasthenia gravis after tumor resection. A comprehensive understanding toward this rare clinical phenomenon is lacking. Recent studies indicate that post-operatively new onset myasthenia gravis (ponoMG) is the result of multiple mechanisms and their interactions, which may be related to the thymoma-mediated production, release and long-term presence of abnormal T cells and autoimmune antibodies in the periphery, as well as the presence of ectopic thymus and late recurrence of thymoma. Preoperative antibody titer is the main predictor. The treatment strategy is based on anticholinesterase drugs and hormonal therapy. In this study, we review the incidence, pathogenesis, predictors, and prevention and treatment strategies of ponoMG.
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@#Objective To evaluate the efficacy and safety of robot-assisted thymectomy (RATS) versus video-assisted thoracoscopic thymectomy (VATS). Methods Web of Science, PubMed, EMbase, The Cochrane Library, Wanfang, VIP and CNKI databases were searched by computer from inception to February 2022. Relevant literatures that compared the efficacy and safety of RATS with those of VATS were screened. The Newcastle-Ottawa Scale (NOS) was used to evaluate the quality of included cohort studies, and Review Manager 5.4 software was utilized to perform a meta-analysis. Results A total of 16 retrospective cohort studies were included, covering a total of 1 793 patients (874 patients in the RATS group and 919 patients in the VATS group). The NOS scores of the included studies were≥7 points. Meta-analysis results revealed that RATS had less intraoperative bleeding (MD=−22.45, 95%CI −34.16 to −10.73, P<0.001), less postoperative chest drainage (MD=−80.29, 95%CI −144.86 to −15.72, P=0.010), shorter postoperative drainage time (MD=−0.69, 95%CI −1.08 to −0.30, P<0.001), shorter postoperative hospital stay (MD=−1.14, 95%CI −1.55 to −0.72, P<0.001) and fewer conversion to thoractomy (OR=0.40, 95%CI 0.23 to 0.69, P=0.001) than VATS; whereas, the operative time (MD=8.37, 95%CI −1.21 to 17.96, P=0.090), incidence of postoperative myasthenia gravis (OR=0.85, 95%CI 0.52 to 1.40, P=0.530), overall postoperative complications rate (OR=0.80, 95%CI 0.42 to 1.50, P=0.480) and tumour size (MD=−0.18, 95%CI −0.38 to 0.03, P=0.090) were not statistically different between the two groups. Conclusion In the aspects of intraoperative bleeding, postoperative chest drainage, postoperative drainage time, postoperative hospital stay and conversion to thoracotomy, RATS has unique advantages over the VATS.
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@#Objective To analyze the clinicopathological characteristics of thymoma patients and the influencing factors for prognosis. Methods Thymoma patients who received treatment in Sichuan Cancer Hospital from March 2015 to March 2021 were collected. Clinical data of the patients were analyzed using Kaplan-Meier and Cox regression analyses. Results A total of 177 patients were included. There were 89 males and 88 females aged 17-88 (52.3±13.0) years, including 160 surgical patients and 17 non-surgical patients. There were 160 patients survived, 17 died of thymoma, and 5 had recurrence and metastasis. Overall, the 1-year, 3-year and 5-year progression-free survival rates were 94.4%, 88.7%, 88.1%, respectively; the 1-year, 3-year and 5-year overall survival rates were 94.9%, 91.5%, 91.0%, respectively. The Kaplan-Meier analysis showed that World Health Organization classification, clinical symptoms, Masaoka-Koga staging, treatment methods and surgery were statistically associated with progression-free survival; clinical symptoms, age, treatment methods and surgery were statistically associated with overall survival (P<0.05). Patients with younger age (P=0.018), without clinical symptoms (P=0.039), and with surgical treatment (P=0.004) had higher overall survival rates; those patients undergoing surgery had a higher progression-free survival rate (P=0.002). Conclusion Age, clinical symptoms and surgical treatment are independent factors influencing the prognosis of patients with thymoma.
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@#Thymoma complicated with polymyositis and myasthenia gravis is a rare case, which can be clearly diagnosed and given symptomatic treatment according to its own diagnostic criteria, imaging and laboratory examinations. This paper reports the clinical data of a thymoma patient with polymyositis and myasthenia gravis admitted to the Seventh Affiliated Hospital of Sun Yat-Sen University, and discusses the possible pathogenesis and treatment methods.
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@#Objective To compare and analyze the occurrence of acute and chronic pain after subxiphoid and transcostal thoracoscopic extended thymectomy. Methods A retrospective analysis was performed on 150 patients who underwent thoracoscopic extended thymectomy in our hospital from July 2020 to June 2022, among whome 30 patients received subxiphoid video-assisted thoracic surgery, and 120 patients received transcostal video-assisted thoracic surgery. The patients were matched by the propensity score matching method. Postoperative pain was evaluated by numeric rating scale (NRS). The intraoperative conditions and postoperative pain incidence were compared between the two groups. Results After matching, 60 patients were enrolled, 30 in each group, including 30 males and 30 females with an average age of 50.78±12.13 years. There was no difference in the general clinical data between the two groups (P>0.05), and no perioperative death. There were statistical differences in the intraoperative blood loss, postoperative drainage volume, postoperative catheter duration, postoperative hospital stay, postoperative pain on 1 d, 2 d, 3 d, 7 d, 3 months and 6 months after the surgery (P<0.05), but there was no statistical difference in the operation time or the postoperative 14 d NRS score (P>0.05). Further univariate and multivariate analyses for postoperative chronic pain showed that surgical method and postoperative 14 d NRS score were risk factors for chronic pain at the 3 months and 6 months after the surgery (P<0.05). Conclusion The subxiphoid thoracoscopic extended thymectomy has advantages over transcostal thoracoscopic surgery in the postoperative acute and chronic pain.
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@#Objective To compare clinical effects of enlarged thymectomy for the treatment of myasthenia gravis (MG) complicated with thymoma via subxiphoid and subcostal arch thoracoscopic resection versus median sternotomy resection. Methods We retrospectively analyzed the clinical data of patients with MG complicated with thymoma admitted in Tangdu Hospital of the Air Force Military Medical University between December 2011 and December 2021. Patients who underwent subxiphoid and subcostal arch thoracoscopic enlarged thymectomy were allocated to a SR group, and patients who underwent median sternotomy enlarged thymectomy were allocated to a MR group. Perioperative outcomes were compared between the two groups. Results A total of 456 patients were collected. There were 51 patients in the MR group, including 30 males and 21 females aged 23-66 (49.5±11.8) years. There were 405 patients in the SR group, among whom 51 patients were matched to the MR group by propensity score matching, including 28 males and 23 females aged 26-70 (47.2±12.2) years. The operations were accomplished successfully in all patients, and no conversion to thoracotomy occurred in the SR group. The SR group had advantages in the operation time, intraoperative blood loss, chest drainage duration, hospital stay time, patients’ satisfaction level, pain score and complications (all P<0.05). No statistical difference was found in the number of intraoperative lymph node dissection stations, number of intraoperative lymph nodes dissected or remission of MG between the two groups (P>0.05). Conclusion Subxiphoid and subcostal arch thoracoscopic enlarged thymectomy and lymphadenectomy is a safe, effective and feasible minimally invasive procedure for the treatment of MG complicated with thymoma.
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@#Objective To compare the clinical efficacy and safety of da Vinci robot with totally no tube (TNT) versus subxiphoid video-assisted thymectomy surgery (SVATS) in the treatment of thymic tumors. Methods From 2019 to 2021, a retrospective analysis was conducted on patients with thymic tumor resection in the Department of Thoracic Surgery, General Hospital of Northern Theater Command. All patients underwent total thymectomy and mediastinal fat removal, and they were divided into a TNT group and a SVATS group according to the operation method. The intraoperative blood loss, conversion rate, postoperative visual analogue score (VAS), postoperative hospital stay time and postoperative complications were compared between the two groups. Results We finally included 435 patiets. There were 168 patients with 83 males and 85 females at an average age of 61.920±9.210 years in the TNT group and 267 patients with 147 males and 120 females at an average age of 61.460±8.119 years in the SVATS group. There was no death or postoperative myasthenic crisis in both groups. There was no statistical difference in postoperative hospital stay (1.540±0.500 d vs. 3.400±0.561 d, P=0.000), intraoperative blood loss (13.450±5.498 mL vs. 108.610±54.462 mL, P=0.000), postoperative 24 h VAS score (4.960±1.757 points vs. 3.600±1.708 points, P=0.000), or postoperative complication rate (3.0% vs. 11.6%, P=0.001). Conclusion TNT is a more efficient, safe, and effective surgical approach for treating thymic tumors, which can shorten hospital stay time and reduce postoperative complications. However, SVATS can minimize postoperative pain.
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@#Objective To analyze the research hotspots and progress of surgical treatment of myasthenia gravis. Methods The top 100 most cited articles on surgical treatment of myasthenia gravis were identified by searching the Web of Science database, and a bibliometric analysis was conducted. Results The publication year of the top 100 most cited articles ranged from 1939 to 2021, and the number of citations ranged from 55 to 850 per article. Most of the included articles were original research articles (75/100), which were mainly retrospective studies (64/75). The United States was the country with the most published articles and most citations, and Annals of Thoracic Surgery was the most sourced journal (n=20). Through VOSviewer analysis, high-density keywords were thymectomy, maximal thymectomy, extended thymectomy, transcervical thymectomy, thymoma, and autoantibodies. Conclusion The scope of surgical resection, surgical approach and pathogenesis are the current hotspots in the field of surgical treatment of myasthenia gravis. It is hoped that this paper can provide references for future researches in this field.
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@#National Comprehensive Cancer Network (NCCN) has updated and released the latest content of NCCN guidelines version 1. 2023 thymomas and thymic carcinomas (known as "guidelines"). The guideline sets standards for the diagnosis and treatment of thymoma and thymic carcinoma based on high quality clinical evidence and the latest advances in research. There have been some updates and revisions in the latest two versions of the guidelines, mainly focusing on the principles of radiotherapy, the principles of systematic therapy, multidisciplinary participation and the improvement of some footnotes, compared with the first version of the guidelines in 2022. In this paper, the contents of the new guideline will be interpreted in order to provide reference for the work of thymoma and thymic carcinoma in our country at the present stage.
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Objective:To explore the prognostic risk factors of thymoma patients after resection, and establish a novel nomogram to predict progression free survival(PFS) of patients with thymoma.Methods:A retrospectively analysis was performed on clinicopathological datas of 267 cases of thymoma patients underwent thymoma resection in Beijing Tongren Hospital from January 2010 to December 2019. The univariate and multivariate Cox risk ratio models were used to analyze the related factors that might affect PFS, and the prediction nomogram of PFS after thymoma resection was established using the screened independent risk factors. Then the predictive ability of the model was evaluated. Results:The univariate analysis showed that age, type of surgery, completeness of resection, WHO histologic classification, TNM stage and postoperative adjuvant therapy were significantly correlated with PFS after thymoma resection( P<0.05). The multivariate analysis showed that only age and TNM stage were independent prognostic factors affecting PFS after thymoma resection( P<0.05). The concordance index( C- index) of the prediction model for the prognosis of thymoma patients established by this method was 0.866(95% CI: 0.809-0.923), which had remarkable predictive efficiency. Conclusion:The nomogram model is constructed and verified based on age and TNM stage, excluding the interference of other clinicopathological factors on prognosis assessment, and which is convenient for clinicians to quickly and individually evaluate the prognosis of patients after thymoma resection.
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Objective:To investigate the clinical characteristics and outcome of patients with voltage-gated potassium channel complex (VGKCc) antibody associated clinical syndromes complicated with myasthenia gravis (MG) with thymoma.Methods:The clinical history, examinations and follow-up prognosis of 2 cases of VGKCc antibodies associated clinical syndromes with MG complicated with thymoma in Qilu Hospital (Qingdao), Cheeloo College of Medicine,Shandong University in September 2020 and December 2020 were reviewed. Related literatures were summarized at the same time.Results:Case 1, a 64-year-old female clinically presented with cognitive impairment, psychosis, and epilepsy seizures, whose serum autoimmune antibody testing showed positive leucine-rich glioma-inhibited 1 (LGI1) antibody, was diagnosed as anti-LGI1 encephalitis,and had history of MG with thymoma. Her symptoms were improved by immunotherapy. Case 2, a 67-year-old male, was diagnosed as MG, and developed cognitive impairment, myokymia and autonomic dysfunction later. His serum autoimmune antibody testing showed positive contactin associated protein-like 2 antibody. Therefore, Morvan syndrome complicated with MG with thymoma was definitely diagnosed. After admission, the patient was improved with immunotherapy and thymoma resection.Conclusions:Patients with VGKCc antibody-associated clinical syndromes complicated with MG have the clinical characteristics of the two diseases simultaneously, and there is also crossover. Immunotherapy and treatment for thymoma are generally effective.
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Objective:To evaluate the safety of thymic surgery in patients aged 65 years and over.Methods:A total of 696 patients who underwent thymectomy/thymoma resection in the Department of Thoracic Surgery of Beijing Hospital from November 2011 to March 2022 were collected and divided into two groups according to the age of 65 years old.The preoperative course of disease, MG stage, dosage of pyridostigmine bromide, American College of Anesthesiologists(ASA)score, surgical method, intraoperative bleeding, postoperative drainage, postoperative complications, Clavien-dindo score(CDC), and myasthenic crisis were recorded and statistically analyzed.Results:A total of 696 patients were enrolled, including 364 males and 332 females, aged 15~86 years, with an average age of 49.1 years.There were 309 patients with thymoma, 565 patients with MG, and 178 patients with both.There were 124 cases in the elderly group(≥65 years old)and 572 cases in the non-elderly group(<65 years old). The incidence of thymoma was higher in the elderly group(54.8 % versus 42.1 %, χ2=6.664, P=0.010), while the incidence of MG was lower(67.7 % versus 84.1 %, χ2=17.827, P<0.001). The ASA score of the elderly group was higher than that of the non-elderly group( χ2=52.372, P=0.000), and the preoperative ventilation function FEV1 and FEV1/FVC were also significantly lower than those of the non-elderly group( z=8.187, 4.580, P=0.000 for all). The drainage volume in the first 3 days after operation and postoperative drainage tube time in the elderly group were significantly higher than those in the non-elderly group( P=0.018, P=0.003). The incidence of postoperative myasthenia crisis in the elderly group was higher than that in the non-elderly group( P=0.034). There was no significant difference in the incidence of postoperative complications between the two groups, but after Clavien-dindo classification, the score of the elderly group was higher than that of the non-elderly group( P=0.003). Although the ASA score and Clavien-dindo score of the elderly group were both higher than those of the non-elderly group, there was no correlation between the two. Conclusions:Although the preoperative ASA score and pulmonary function of elderly patients were poorer than those in the non-elderly group, while the incidence of postoperative myasthenia crisis was higher, and the incidence of postoperative complications was not higher, the Clavien-dindo classification, however, was higher in elderly patients than that of the non-elderly group.After careful preoperative evaluation and strengthening perioperative management, most elderly patients can receive thymus surgery safely with acceptable risks.
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Aims: Thymectomy specimens are uncommon in routine histopathology practice. However, awareness of various pathologic entities and definite reporting of these specimens is paramount to optimal patient management. Our objective was to determine the histomorphologic spectrum of thymectomy specimens spanning the non-neoplastic, benign to malignant spectrum. Methods and Results: Thymectomies received over an 8-year period were retrospectively analyzed by reviewing clinical details and histologic findings in detail, incorporating the latest World Health Organization (WHO) 2015 histologic classification. A total of 303 thymectomy specimens (179 males/124 females, mean age 45.3 years [3–84 years]) were included. Around 51.2% (n = 155) patients had associated myasthenia gravis (MG), while 17.5% (n = 53) had incidentally detected anterior mediastinal mass (AMM). Non-neoplastic and benign pathologies comprised 31% (n = 94) cases and showed stronger association with MG (P = 0.009). Thymic follicular hyperplasia (TFH) was the commonest non-neoplastic pathology (n = 32), while the benign tumor group included thymic hemangioma/lymphangioma, thymolipoma, and ectopic parathyroid adenoma. Thymic epithelial tumors (TETs) comprised 64.7% cases, with majority being thymomas (185/303; 61.1%). Thymoma type B2 was the commonest histologic subtype and Stage I/T1 was the most frequent stage. Type A and AB thymomas affected older patients (P = 0.005) and were in lower stage (both Masaoka and American Joint Committee on Cancer [AJCC]) than type B thymomas (P = 0.007). No significant association between MG and thymoma subtype, patient sex or Masaoka stage was seen (P > 0.05). Thymic carcinomas comprised 11 cases and showed no association with MG (0/11, P < 0.001); squamous cell carcinoma was the commonest histologic type (8/11; 72.7%). Conclusion: TETs are the commonest thymic lesions; however, a diverse spectrum of pathologic processes can affect the thymus.
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Background: Myasthenia gravis (MG) is a prototypic T-cell-dependent antibody-mediated autoimmune disease that leads to ocular or generalized muscular weakness. The disease is most commonly caused by antibodies to the acetylcholine receptors, often with underlying thymic pathology. Aims: This study is aimed at analyzing the pathological spectrum of the excised thymuses in patients with myasthenia. Materials and Methods: This was a retrospective 10-year study of 68 thymectomy specimens performed as a part of the treatment of patients with MG. Statistical Analysis: Nil. Results: There were 47 males and 21 females (male to female ratio of 2.2:1) with a mean age of 41 years. Only three patients presented with ocular myasthenia. The thymus was normal in 9 patients (13.2%) and atrophic in 17 patients (25%). Follicular hyperplasia and thymomas were seen in 6 and 36 patients, respectively. Conclusion: The thymectomies performed in patients of MG had a fairly variable spectrum on histology; the thymic tumors were predominantly of the cortical phenotype.
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Objective:To analyze the clinical efficacy of different treatment modalities and prognostic factors of patients with Masaoka-Koga stage Ⅲ thymoma.Methods:Clinical data of patients diagnosed with Masaoka-Koga stage Ⅲ thymoma admitted to Affiliated Cancer Hospital of Zhengzhou University from January 2000 to December 2018 were analyzed retrospectively. A total of 133 patients had complete treatment and follow-up data. Kaplan-Meier method was used to calculate the cumulative survival rate, log-rank method was used to compare the survival between two groups, and Cox regression model was used for multivariate analysis.Results:The median follow-up time was 50 months (3-221 months). The median overall survival (OS) was 51 (3-221) months, and the median disease-free survival (DFS) was 45 (2-221) months. The survival rate in the radical surgery group was better than that in the palliative surgery group. The 5- and 10-year OS rates in radical surgery group were 88.2% and 74.4% respectively, while in palliative surgery group were 51.8% and 32.4% respectively ( P<0.001). The 5- and 10-year DFS rates in radical surgery group were 72.2% and 45.5%, respectively, while in palliative surgery group were 32.3% and 16.1% respectively ( P=0.001). The OS in the surgery combined with radiotherapy group was better than that in the surgery alone group. The 5- and 10-year OS rates in the radical surgery group were 82.8% and 64.2% respectively, while in the palliative surgery group were 55.8% and 50.2% ( P=0.033). There was no significant difference in DFS between two groups ( P=0.176). Multivariate analysis showed that age < 50 years old ( HR=0.264, P=0.001), radical resection ( HR=0.134, P<0.001), surgery combined with radiotherapy ( HR=2.778, P=0.009) were independently associated with better OS. Age < 50 years old ( HR=0.550, P=0.046), radical resection ( HR=0.555, P=0.042), and invasion of single organ ( HR=0.111, P=0.003) were independently associated with better DFS. Conclusions:OS and DFS in patients undergoing radical surgery are significantly better than those in their counterparts treated with palliative surgery, which is the most important factor affecting prognosis. Surgery combined with radiotherapy yields better OS. It is necessary to design a rigorous and reasonable multicenter prospective study to evaluate the efficacy of various treatment modalities and prognostic factors.