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The Thymectomy Trial in Non-Thymomatous Myasthenia Gravis Patients Receiving Prednisone (MGTX) showed that thymectomy combined with prednisone was superior to prednisone alone in improving clinical status as measured by the Quantitative Myasthenia Gravis (QMG) score in patients with generalised non-thymomatous myasthenia gravis at 3 years. We investigated the long-term effects of thymectomy up to 5 years on clinical status, medication requirements, and adverse events. We did a rater-blinded 2-year extension study at 36 centres in 15 countries for all patients who completed the randomised controlled MGTX and were willing to participate. MGTX patients were aged 18 to 65 years at enrolment, had generalised non-thymomatous myasthenia gravis of less than 5 years' duration, had acetylcholine receptor antibody titres of 1·00 nmol/L or higher (or concentrations of 0·50–0·99 nmol/L if diagnosis was confirmed by positive edrophonium or abnormal repetitive nerve stimulation, or abnormal single fibre electromyography), had Myasthenia Gravis Foundation of America Clinical Classification Class II–IV disease, and were on optimal anticholinesterase therapy with or without oral corticosteroids. In MGTX, patients were randomly assigned (1:1) to either thymectomy plus prednisone or prednisone alone. All patients in both groups received oral prednisone at doses titrated up to 100 mg on alternate days until they achieved minimal manifestation status. The primary endpoints of the extension phase were the time-weighted means of the QMG score and alternate-day prednisone dose from month 0 to month 60. Analyses were by intention to treat. The trial is registered with ClinicalTrials.gov, number NCT00294658. It is closed to new participants, with follow-up completed. Of the 111 patients who completed the 3-year MGTX, 68 (61%) entered the extension study between Sept 1, 2009, and Aug 26, 2015 (33 in the prednisone alone group and 35 in the prednisone plus thymectomy group). 50 (74%) patients completed the 60-month assessment, 24 in the prednisone alone group and 26 in the prednisone plus thymectomy group. At 5 years, patients in the thymectomy plus prednisone group had significantly lower time-weighted mean QMG scores (5·47 [SD 3·87] vs 9·34 [5·08]; p=0·0007) and mean alternate-day prednisone doses (24 mg [SD 21] vs 48 mg [29]; p=0·0002) than did those in the prednisone alone group. 14 (42%) of 33 patients in the prednisone group, and 12 (34%) of 35 in the thymectomy plus prednisone group, had at least one adverse event by month 60. No treatment-related deaths were reported during the extension phase. At 5 years, thymectomy plus prednisone continues to confer benefits in patients with generalised non-thymomatous myasthenia gravis compared with prednisone alone. Although caution is appropriate when generalising our findings because of the small sample size of our study, they nevertheless provide further support for the benefits of thymectomy in patients with generalised non-thymomatous myasthenia gravis. National Institutes of Health, National Institute of Neurological Disorders and Stroke.

Background The aim of this study was to evaluate the safety and effectiveness of robot‐assisted thymectomy (RAT) in large anterior mediastinal tumors (AMTs) (size ≥6 cm) compared with video‐assisted thymectomy (VAT) and open surgery. Methods A total of 132 patients with large AMTs who underwent surgical resection from January 2016 to June 2022 were included in this study. A total of 61 patients underwent RAT, 36 patients underwent VAT and 35 patients underwent open surgery. Perioperative outcomes were compared. Results There were no significant differences in tumor size (p = 0.141), or pathological types (p = 0.903). Compared with the open group, the RAT and VAT groups were associated with a shorter operation time (115.00 vs. 160.00, p = 0.012; 122.50 vs. 160.00, p = 0.071), and less blood loss (50.00 vs. 200.00, p < 0.001; 50.00 vs. 200.00, p < 0.001), respectively. The rate of conversion in the RAT group was similar to that in the VAT group (6.56% vs. 13.89%, p = 0.229). Concomitant resection was less frequently performed in the VAT group than in the RAT and open groups (5.56% vs. 31.15%, p = 0.040; 5.56% vs. 31.43%, p = 0.006). VAT patients had a lower drainage volume (365.00 vs. 700.00 and 910.00 mL, p < 0.001), shorter duration of chest tube (2.00 vs. 3.00 and 4.00, p < 0.001), and shorter hospital stay (5.00 vs. 6.00 and 7.00, p < 0.001) than the RAT and open groups. There was no 30‐day mortality in any group. No difference was seen in R0 resection rates (p = 0.846). The postoperative complication rates were similar among the three groups (p = 0.309). Total in‐hospital costs (66493.90 vs. 33581.05 and 42876.40, p < 0.001) were significantly higher in the RAT group. Conclusions RAT is safe and effective for the resection of large AMTs compared to VAT and open surgery. Vascular resection in RAT is technically feasible. A long‐term follow‐up is required. The robot‐assisted thymectomy (RAT) can be performed using various approaches. The sub‐xiphoid approach is routinely selected for centered and advanced large AMTs in our center; it can provide excellent visualization for exposing the proximal and distal ends of the innominate vein, which is convenient for resection of the invaded innominate vein, even for partial resection of the superior vena cava (SVC).

The function of the thymus in human adults is unclear, and routine removal of the thymus is performed in a variety of surgical procedures. We hypothesized that the adult thymus is needed to sustain immune competence and overall health. We evaluated the risk of death, cancer, and autoimmune disease among adult patients who had undergone thymectomy as compared with demographically matched controls who had undergone similar cardiothoracic surgery without thymectomy. T-cell production and plasma cytokine levels were also compared in a subgroup of patients. After exclusions, 1420 patients who had undergone thymectomy and 6021 controls were included in the study; 1146 of the patients who had undergone thymectomy had a matched control and were included in the primary cohort. At 5 years after surgery, all-cause mortality was higher in the thymectomy group than in the control group (8.1% vs. 2.8%; relative risk, 2.9; 95% confidence interval [CI], 1.7 to 4.8), as was the risk of cancer (7.4% vs. 3.7%; relative risk, 2.0; 95% CI, 1.3 to 3.2). Although the risk of autoimmune disease did not differ substantially between the groups in the overall primary cohort (relative risk, 1.1; 95% CI, 0.8 to 1.4), a difference was found when patients with preoperative infection, cancer, or autoimmune disease were excluded from the analysis (12.3% vs. 7.9%; relative risk, 1.5; 95% CI, 1.02 to 2.2). In an analysis involving all patients with more than 5 years of follow-up (with or without a matched control), all-cause mortality was higher in the thymectomy group than in the general U.S. population (9.0% vs. 5.2%), as was mortality due to cancer (2.3% vs. 1.5%). In the subgroup of patients in whom T-cell production and plasma cytokine levels were measured (22 in the thymectomy group and 19 in the control group; mean follow-up, 14.2 postoperative years), those who had undergone thymectomy had less new production of CD4+ and CD8+ lymphocytes than controls (mean CD4+ signal joint T-cell receptor excision circle [sjTREC] count, 1451 vs. 526 per microgram of DNA [P = 0.009]; mean CD8+ sjTREC count, 1466 vs. 447 per microgram of DNA [P<0.001]) and higher levels of proinflammatory cytokines in the blood. In this study, all-cause mortality and the risk of cancer were higher among patients who had undergone thymectomy than among controls. Thymectomy also appeared be associated with an increased risk of autoimmune disease when patients with preoperative infection, cancer, or autoimmune disease were excluded from the analysis. (Funded by the Tracey and Craig A. Huff Harvard Stem Cell Institute Research Support Fund and others.).

Background: Minimally invasive thymectomy is fast becoming the preferred approach for myasthenia gravis and non-invasive thymoma. The most commonly employed approach for minimally invasive thymectomy is the lateral thoracic approach. Safe achievement of radical resection requires adequate visualisation of both the phrenic nerves along their entire course. In our experience, such visualisation is rather difficult with unilateral transthoracic approaches. We herein describe our technique and initial experience of 25 cases with subxiphoid robotic thymectomy (SRT) for myasthenia gravis with or without thymoma. To the best of our knowledge, this is the first such report from India. Subjects and Methods: We retrospectively analysed data of patients who underwent SRT at our centre from June 2017 to September 2018. Twenty-five consecutive patients were analysed, and demographic data, total duration of the procedure, console time, blood transfusion requirement, duration of chest drainage, length of hospital stay, pain score on post-operative day (POD) 1 and day of discharge and post-operative morbidity and mortality within 90 days were recorded. Results: A total of 25 patients underwent SRT. All our patients had myasthenia gravis with 4 of them having thymoma. There were 11 males and 14 females with mean age of 29.30 years (range 23-48). The mean console time was 102.85 min (range 88-120) while the mean total operative time was 199.14 (range 180-220). On first POD 1, visual analogue scale score average was 5, and at discharge, it was 2. There was no 30-day or 90-day mortality. All cases of thymoma had a complete R0 resection. Conclusion: Our experience suggests that subxiphoid approach offers a good operative view of the thymus in cervical region along with easy identification of bilateral phrenic nerves. Thus, SRT can be performed safely with comparable results.

High-dose prednisone use, lasting several months or longer, is the primary initial therapy for myasthenia gravis (MG). Upwards of a third of patients do not respond to treatment. Currently no biomarkers can predict clinical responsiveness to corticosteroid treatment. We conducted a discovery-based study to identify treatment responsive biomarkers in MG using sera obtained at study entry to the thymectomy clinical trial (MGTX), an NIH-sponsored randomized, controlled study of thymectomy plus prednisone versus prednisone alone. We applied ultra-performance liquid chromatography coupled with electro-spray quadrupole time of flight mass spectrometry to obtain comparative serum metabolomic and lipidomic profiles at study entry to correlate with treatment response at 6 months. Treatment response was assessed using validated outcome measures of minimal manifestation status (MMS), MG-Activities of Daily Living (MG-ADL), Quantitative MG (QMG) score, or a strictly defined composite measure of response. Increased serum levels of phospholipids were associated with treatment response as assessed by QMG, MMS, and the Responders classification, but all measures showed limited overlap in metabolomic profiles, in particular the MG-ADL. A panel including histidine, free fatty acid (13:0), γ-cholestenol and guanosine was highly predictive of the strictly defined treatment response measure. The AUC in Responders' prediction for these markers was 0.90 irrespective of gender, age, thymectomy or baseline prednisone use. Pathway analysis suggests that xenobiotic metabolism could play a major role in treatment resistance. There was no association with outcome and gender, age, thymectomy or baseline prednisone use. We have defined a metabolomic and lipidomic profile that can now undergo validation as a treatment predictive marker for MG patients undergoing corticosteroid therapy. Metabolomic profiles of outcome measures had limited overlap consistent with their assessing distinct aspects of treatment response and supporting unique biological underpinning for each outcome measure. Interindividual variation in prednisone metabolism may be a determinate of how well patients respond to treatment.

Background Surgery for thymic cancers is considered the key of curative treatment. Preoperative patients’ characteristics and intraoperative features might influence postoperative outcome. We aim to verify short-term outcomes and possible risk factors for complications after thymectomy. Methods We retrospectively investigated patients undergoing surgery for thymoma or thymic carcinoma in the period between January 1, 2008, and December 31, 2021, in our department. Preoperative features, surgical technique (open, bilateral VATS, RATS), intraoperative characteristics and incidence of postoperative complications (PC) were analyzed. Results We included in the study 138 patients. Open surgery was performed in 76 patients (55.1%), in 36 VATS (26.1%) and in 26 RATS (36.1%). Resection of one or more adjacent organs due to neoplastic infiltration was required in 25 patients. PC appeared in 25 patients (52% Clavien–Dindo grade I, 12% grade IVa). Open surgery had a higher incidence of PC ( p  < 0.001), longer postoperative in-hospital stay ( p  = 0.045) and larger neoplasm ( p  = 0.006). PC were significant related to pulmonary resection ( p  = 0.006), phrenic nerve resection ( p  = 0.029), resection of more than one organ ( p  = 0.009) and open surgery ( p  = 0.001), but only extended surgery of more organs was confirmed as independent prognostic factor for PC ( p  = 0.0013). Patients with preoperative myasthenia symptoms have a trend toward stage IVa complications ( p  = 0.065). No differences were observed between outcomes of VATS and RATS. Conclusions Extended resections are related to a higher incidence of PC, while VATS and RATS guarantee a lower incidence of PC and shorter postoperative stay even in patients that require extended resections. Symptomatic myasthenia patients might have a higher risk toward more severe complications.

Recent studies have raised concerns about thymectomy's deleterious effects. However, this conclusion was not exclusive to patients with myasthenia gravis (MG). The objective of this study was to test this hypothesis in thymectomy patients, regardless of their MG status. We conducted a retrospective case-control study to analyze clinical and radiological data from 1 January 2010 to 30 November 2023. Patients were divided into four groups: MG with (MG-Thy) or without thymectomy (MG-NO-Thy); thoracoscopic surgery without thymectomy (Surgery-NO-Thy) and Non-MG with thymectomy (Non-MG-Thy). We identified a total of 456 patients (n=41, MG-Thy; n= 278, MG-NO-Thy; n=65, Non-MG-Thy; and n=72, Surgery-NO-Thy). The median ages were as follows: MG-Thy, 45.6 years (range: 22-79); MG-NO-Thy, 65 years (13-93); Non-MG-Thy, 59.8 (19-85) years; and Surgery-NO-Thy, 59.8 years (range: 19-85) (p<0.001). The median follow-up times were 5.5 years in MG-Tym, 3 in MG-NO-Thy, 3.9 in Non-MG-Thy, and 4.7 years in Surgery-NO-Thy. A thymic mass was detected with chest computed tomography (CT) in 56% (23/41) of the MG-Thy cohort and in all the Non-MG-Thy cohort. Thymic pathology in the MG-Thy group showed normal/fat atrophic thymus in 31.7% (13/41), hyperplasia in 26.8% (11/41), thymic cyst in 2.4% (1/41), and malignant in 39% (16/41). Thymic pathology in the non-MG group showed hyperplasia, fat, or normal thymus in 16.9% (11/65); thymic cyst in 18.5% (12/65); malignant thymoma in 60% (39/65); and others in 4.6% (3/65). The death rate was the lowest in the MG-Thy group, compared to the non-MG groups and the MG-No-Thy group. Specifically, death occurred in zero cases in the MG-Thy group, while it occurred in 13.8% (9/65) of the thymectomized non-MG group and in 35.6% (99/278) of the MG-without thymectomy group. Excluding late-onset MG patients (LOMG), the death incidence was 14.4% (15/104). The prevalence of autoimmune diseases before thymectomy was 14.6% (6/41) in the MG-Thy group versus 12.3% (8/65) in the Non-MG-Thy group, with three new cases post thymectomy in non-MG group. Post thymectomy cancer incidence was zero in the MG-Thy group, versus 16.2% (45/278) in the MG-NO-Thy group. The benefits of thymectomy outweigh potential risks for patients with MG or patients with thymic malignancies. Incidental thymectomy should be avoided. This call for reevaluation of thymectomy especially for non-neoplastic causes.

The last 10 years has brought transformative developments in the effective treatment of myasthenia gravis (MG). Beginning with the randomized trial of thymectomy in myasthenia gravis that demonstrated efficacy of thymectomy in nonthymomatous MG, several new treatment approaches have completed successful clinical trials and regulatory launch. These modalities, including B cell depletion, complement inhibition, and blockade of the neonatal Fc receptor, are now in use, offering prospects of sustained remission and neuromuscular protection in what is a long-term disease. In this review, we update our clinico-immunological review of 2016 with these important advances, examine their role in treatment algorithms, and focus attention on key issues of biomarkers for prognostication and the growing cohort of older patients, both those with long-term disease, and late-onset MG (‘LOMG’). We close by expressing our four hopes for the next 5–10 years: improvements in laboratory medicine to facilitate rapid diagnosis, effective strategies for neuromuscular protection, more research into and better understanding of pathophysiology and treatment response in older individuals, and the potentially transformative role of therapies aimed at delivering a durable response such as chimeric antigen receptor (CAR) T cells. Our postscript summarizes some emerging themes in the field of serological and online biomarkers, which may develop greater stature in the next epoch.

Objective The efficacy and safety of subxiphoid thoracoscopic thymectomy (SVATS) for early thymoma are unknown. The purposes of this meta-analysis were to evaluate the effectiveness and safety of SVATS for early thymoma, to compare it with unilateral intercostal approach video thoracoscopic surgery (IVATS) thymectomy, and to investigate the clinical efficacy of modified subxiphoid thoracoscopic thymectomy (MSVATS) for early anterior mediastinal thymoma. Methods Original articles describing subxiphoid and unilateral intercostal approaches for thoracoscopic thymectomy to treat early thymoma published up to March 2023 were searched from PubMed, Embase, and the Cochrane Library. Standardized mean differences (SMDs) and 95% confidence intervals (CIs) were calculated and analyzed for heterogeneity. Clinical data were retrospectively collected from all Masaoka stage I and II thymoma patients who underwent modified subxiphoid and unilateral intercostal approach thoracoscopic thymectomies between September 2020 and March 2023. The operative time, intraoperative bleeding, postoperative drainage, extubation time, postoperative hospital stay, postoperative visual analog pain score (VAS), and postoperative complications were compared, and the clinical advantages of the modified subxiphoid approach for early-stage anterior mediastinal thymoma were analyzed. Results A total of 1607 cases were included in the seven studies in this paper. Of these, 591 cases underwent SVATS thymectomies, and 1016 cases underwent IVATS thymectomies. SVATS thymectomy was compared with IVATS thymectomy in terms of age (SMD = − 0.09, 95% CI: −0.20 to − 0.03, I 2  = 20%, p  = 0.13), body mass index (BMI; SMD = − 0.10, 95% CI: −0.21 to − 0.01, I 2  = 0%, p  = 0.08), thymoma size (SMD = − 0.01, 95% CI: −0.01, I 2  = 0%, p  = 0.08), operative time (SMD = − 0.70, 95% CI: −1.43–0.03, I 2  = 97%, p  = 0.06), intraoperative bleeding (SMD = − 0.30. 95% CI: −0.66–0.06, I 2  = 89%, p  = 0.10), time to extubation (SMD = − 0.34, 95%CI: −0.73–0.05, I 2  = 91%, p  = 0.09), postoperative hospital stay (SMD = − 0.40, 95% CI: −0.93–0.12, I 2  = 93%, p  = 0.13), and postoperative complications (odds ratio [OR] = 0.94, 95% CI: 0.42–2.12, I 2  = 57%, p  = 0.88), which were not statistically significantly different between the SVATS and IVATS groups. However, the postoperative drainage in the SVATS group was less than that in the IVATS group (SMD = − 0.43, 95%CI: −0.84 to − 0.02, I 2  = 88%, p  = 0.04), and the difference was statistically significant. More importantly, the postoperative VAS was lower in the SVATS group on days 1 (SMD = − 1.73, 95%CI: −2.27 to − 1.19, I 2  = 93%, p  < 0.00001), 3 (SMD = − 1.88, 95%CI: −2.84 to − 0.81, I 2  = 97%, p  = 0.0005), and 7 (SMD = − 1.18, 95%CI: −2.28 to − 0.08, I 2  = 97%, p  = 0.04) than in the IVATS group, and these differences were statistically significant. A total of 117 patients undergoing thoracoscopic thymectomy for early thymoma in the Department of Thoracic Surgery of the Second Hospital of Jilin University were retrospectively collected and included in the analysis, for which a modified subxiphoid approach was used in 42 cases and a unilateral intercostal approach was used in 75 cases. The differences between the two groups (MSVATS vs. IVATS) in general clinical characteristics such as age, sex, tumor diameter, Masaoka stage, Word Health Organization (WHO) stage, and intraoperative and postoperative conditions, including operative time, postoperative drainage, extubation time, postoperative hospital stay, and postoperative complication rates, were not statistically significant ( p  > 0.05), while BMI, intraoperative bleeding, and VAS on postoperative days 1, 3, and 7 were all statistically significant ( p  < 0.05) in the MSVATS group compared with the IVATS group. Conclusion The meta-analysis showed that the conventional subxiphoid approach was superior in terms of postoperative drainage and postoperative VAS pain scores compared with the unilateral intercostal approach. Moreover, the modified subxiphoid approach had significant advantages in intraoperative bleeding and postoperative VAS pain scores compared with the unilateral intercostal approach. These results indicate that MSVATS can provide more convenient operation conditions, a better pleural cavity view, and a more complete thymectomy in the treatment of early thymoma, indicating that is a safe and feasible minimally invasive surgical method.

Background/Objectives: Total thymectomy is currently the gold standard operation for treating thymoma. However, recent studies have suggested the potential health consequences of thymus removal in adults, including possible increased autoimmune disease and all-cause mortality. In this context, we assess oncologic outcomes following total vs. partial thymectomy for early-stage thymoma. Methods: We identified patients diagnosed with WHO types A–B3 thymoma between 2010–2021 from a national hospital-based dataset. We excluded patients with stage II or higher disease, open resections and perioperative chemo-/radiation therapy. We stratified patients into total and partial thymectomy cohorts. We used propensity score matching to minimize confounding, Kaplan–Meier analysis to estimate survival, and Cox proportional hazards to identify associations. Results: Of 1598 patients with early-stage thymoma, 495 (31.0%) underwent partial and 1103 (69.0%) total thymectomy. Patients undergoing partial thymectomy were similar in sex (female 53.7% vs. 53.4%; p = 0.914), race (white 74.5% vs. 74.0%; p = 0.921), comorbidities (0 in 77.0% vs. 75.5%; p = 0.742), and tumor size (48.7 mm vs. 50.4 mm; p = 0.455) compared to total thymectomy. There were no differences in 30-day (0.8% vs. 0.6%, p = 0.747) or 90-day mortality (0.8% vs. 0.8%, p > 0.999), which persisted after matching. Moreover, 10-year survival was similar in both unmatched (p = 0.471) and matched cohorts (p = 0.828). Partial thymectomy was not independently associated with survival (aHR = 1.00, p = 0.976). Conclusions: In patients with early-stage thymoma, partial and total thymectomy were associated with similar short- and long-term outcomes. In light of recent attention to the role of the thymus gland, the results add important insights to shared decision-making discussions.