Cardiac herniation post left upper lobectomy and thymectomy: a case report.

BACKGROUND: Cardiac herniation occurs when there is a residual pericardial defect post thoracic surgery and is recognised as a rare but fatal complication. It confers a high mortality and requires immediate surgical correction upon recognition. We present a case of cardiac herniation occurring post thymectomy and left upper lobectomy. CASE PRESENTATION: Initial presentation: A 48-year-old male, hypertensive smoker presented with progressive breathlessness and was found to have a left upper zone mass confirmed on CT biopsy as carcinoid of unclear origin. PET-CT revealed avidity in a left anterior mediastinal area, left upper lobe (LUL) lung mass, mediastinal lymph nodes, and a right thymic satellite nodule. Intraoperatively: Access via left thoracotomy and sternotomy. The LUL tumour involved the left thymic lobe (LTL), left superior pulmonary vein (LSPV), left phrenic nerve and intervening mediastinal fat and pericardium, which were resected en-masse. The satellite nodule in the right thymic lobe (RTL) was adjacent to the junction between the left innominate vein and superior vena cava (SVC). The pericardium was resected from the SVC to the left atrial appendage. Clinical deterioration: Initially the patient was doing well clinically on day 1, however there was sudden bradycardia, hypotension, clamminess, and oligoanuria, with raised central venous pressures and troponins. ECG: no capture in leads V1-2, but positive deflections seen on posterior leads. Echo: no acoustic windows, but good windows seen posteriorly. CXR: left mediastinal shift. Redo operation: After initial resuscitation and stabilisation on the intensive care unit, on day 2 a redo-sternotomy revealed cardiac herniation into the left thoracic cavity with the left ventricular apex pointing towards the spine, and inferior caval kinking. After reduction and repair of the pericardial defect with a fenestrated GoreTex patch, the patient recovered well with complete resolution of the ECG and CXR. CONCLUSION: Cardiac herniation can even occur following sub-pneumonectomy lung resections and should be considered as a differential when faced with a sudden clinical deterioration, warranting early surgical correction.

The modified Lyon's position: an alternative approach to robotic thymectomy.

The conventional supine position for robotic thymectomy may present challenges in accessing the lower thymic horns, particularly in cases requiring extensive resection of mediastinal fat. To address this issue, the authors advocate for a lateral patient position during the procedure, emphasizing optimized access to the thymic horns and improved procedural efficacy. The lateral approach involves specific trocar placements and port arrangements to minimize conflicts between instruments. This report proposes an innovative approach to robotic thymectomy for patients diagnosed with thymoma or thymic hyperplasia associated with myasthenia gravis.

Generalized myasthenia gravis with acetylcholine receptor antibodies: A guidance for treatment.

BACKGROUND: Generalized myasthenia gravis (MG) with antibodies against the acetylcholine receptor is a chronic disease causing muscle weakness. Access to novel treatments warrants authoritative treatment recommendations. The Nordic countries have similar, comprehensive health systems, mandatory health registers, and extensive MG research. METHODS: MG experts and patient representatives from the five Nordic countries formed a working group to prepare treatment guidance for MG based on a systematic literature search and consensus meetings. RESULTS: Pyridostigmine represents the first-line symptomatic treatment, while ambenonium and beta adrenergic agonists are second-line options. Early thymectomy should be undertaken if a thymoma, and in non-thymoma patients up to the age of 50-65 years if not obtaining remission on symptomatic treatment. Most patients need immunosuppressive drug treatment. Combining corticosteroids at the lowest possible dose with azathioprine is recommended, rituximab being an alternative first-line option. Mycophenolate, methotrexate, and tacrolimus represent second-line immunosuppression. Plasma exchange and intravenous immunoglobulin are used for myasthenic crises and acute exacerbations. Novel complement inhibitors and FcRn blockers are effective and fast-acting treatments with promising safety profiles. Their use depends on local availability, refunding policies, and cost-benefit analyses. Adapted physical training is recommended. Planning of pregnancies with optimal treatment, information, and awareness of neonatal MG is necessary. Social support and adaptation of work and daily life activities are recommended. CONCLUSIONS: Successful treatment of MG rests on timely combination of different interventions. Due to spontaneous disease fluctuations, comorbidities, and changes in life conditions, regular long-term specialized follow-up is needed. Most patients do reasonably well but there is room for further improvement. Novel treatments are promising, though subject to restricted access due to costs.

The Impact Of Thymectomy In Thymomatous And Nonthymomatous Myasthenia Gravis - The Experience Of A Tertiary Center.

INTRODUCTION: Thymectomy remains a mainstay of treatment in Thymomatous (T) and Nonthymomatous (nT) Myasthenia Gravis (MG), with improved clinical outcomes and reduced need for medical treatment, however, there is little research regarding long-term follow-up. We aim to assess the impact of surgery on the long-term outcome of patients with MG at our center. METHODS: Retrospective analyses of MG patients submitted to thymectomy between 2007 and 2017 at the thoracic surgery department of CHUC. Clinical assessment was performed according to the MG Foundation of America (MGFA) Clinical Classification (cMGFA). The follow-up was categorized according to the MGFA Post-intervention Status (MGFA-PIS) and cMGFA. Statistical analysis was performed with SPSS, to a significance level of 5%. RESULTS: Thirty-seven patients underwent extended thymectomy and 67.6% were female. Median age at diagnosis was 46.68±19.2 years. Most patients (83.8%) had anti-acetylcholine receptor antibodies and 81.1% had generalized forms of MG. Many patients (67.6%) had surgery less than 12 months after the clinical diagnosis. TMG was present in 19 (51.4%) patients. Compared to nTMG, these patients were older (54.06±17.9 vs 40.17±19.4 years) and most were men (52.9% vs 16.7%). We obtained a good outcome in most patients in the first (81.1%), second (86.1%), and fifth (84.8%) year of follow-up. There was a shift towards better prognosis categories in the good outcome group: 9.1% CSR, 3.0% PR, and 66,7% MM in the fifth year. Preoperative medical treatment did not influence the long-term follow-up outcome. A shorter time to surgery (< 12 months) correlated with better outcomes at year 5 (p=0.016). CONCLUSION: Thymectomy led to a sustained clinical improvement in our cohort, allowing for a reduced need for medication. A shorter time to surgery seems to have a positive influence on long-term prognosis. We expect that an extended follow-up would improve our results.

Steroid-resistant minimal change nephrotic syndrome associated with thymoma treated effectively with rituximab following thymectomy and cyclosporine: a case report.

BACKGROUND: Minimal change nephrotic syndrome (MCNS) can be complicated by thymoma; however, no standard therapy for thymoma-associated MCNS has yet been established. We herein describe a case of steroid-resistant MCNS associated with thymoma, treated effectively with rituximab. CASE PRESENTATION: A 71-year-old Japanese man was referred to our department with severe proteinuria (20 g/gCr). Renal biopsy showed minimal change disease and computed tomography revealed an anterior mediastinal mass. Based on these findings, he was diagnosed with thymoma-associated MCNS. He was treated with oral prednisolone (50 mg/day) and cyclosporine, and underwent thymectomy and plasma exchange. However, no improvement in proteinuria was observed. He therefore received intravenous rituximab 500 mg, resulting in a marked decrease in proteinuria from 5328 to 336 mg/day after 1 week. CONCLUSIONS: This case suggests that rituximab might be an effective therapy in patients with steroid-resistant MCNS associated with thymoma.

Myasthenia Gravis with Toxic Goiter: Challenges with Management in a Low-Resource Setting in Africa; Review of Literature and Case Report.

ABSTRACT: Myasthenia gravis (MG) is an antibody-mediated autoimmune disease with the cardinal feature being exertional voluntary skeletal muscle weakness and fatigability. It can be an isolated finding or in association with other autoimmune conditions such as Hashimoto's thyroiditis, Graves' disease, systemic lupus erythematosus (SLE), or rheumatoid arthritis. Thymectomy is recommended for most patients with MG whose symptoms begin before the age of 60 years. Patients with thymoma or thymic hyperplasia do respond to thymectomy compared to those without thymoma or enlarged thymus. Those with enlarged goiter would benefit from thyroidectomy. The management of these patients requires a multidisciplinary approach as performed in a low-resource setting. We are reporting the case of a 24-year-old who presented with MG with toxic goiter and had good control on medication. A computed tomography scan of the chest showed a superior mediastinal mass and a soft tissue scan of the neck was done which showed a diffusely enlarged thyroid gland. She subsequently had thymectomy and subtotal thyroidectomy with a satisfactory outcome. We highlight this case to show that MG with thymoma and goiter could coexist. Reports of such findings are infrequently reported in our environment.

Pure white cell aplasia before and after thymectomy in the rare conundrum of thymoma: A case report and review of the literature.

RATIONALE: Pure white cell aplasia (PWCA) is a rare paraneoplastic syndrome that occurs in patients with thymomas. Currently, the pathogenesis and treatment of this disease remain in the exploratory stage. PATIENT CONCERNS: We report a 68-year-old woman with thymoma experienced PWCA involvement as her first presentation. The patient had high fever and agranulocytosis at the onset of the disease. The white blood cell count in the complete blood count was 1.9 × 109/L with a neutrophil of 0.1 × 109/L. The bone marrow aspirates showed decreased granulocyte proliferation. Computed tomography showed a large mass in the anterior mediastinum. DIAGNOSES: The final diagnosis of our patient was PWCA and thymoma. INTERVENTIONS: She underwent a thymectomy and cyclosporine A administration during first remission. OUTCOMES: Long-term remission was achieved following the readministration of cyclosporine A after the disease recurrence. LESSONS: PWCA or agranulocytosis with thymoma has been confirmed to be an extremely rare disease. Thymomas with PWCA correlate with autoimmunity. From this case study and the literature review, we concluded that the pathogenesis of thymomas in PWCA is mainly related to the activation of autoreactive T cells. Thymectomy and the immunosuppressive drug, cyclosporine A, were chosen for treatment. The patient's granulocyte levels were unable to recover after surgery because of the inability to promptly clear activated T cells. After surgery, cyclosporine A continued to take for a long time. Thymectomy combined with prolonged cyclosporine A administration may be an effective method for treating this rare disease.

Robot-assisted surgery outperforms video-assisted thoracoscopic surgery for anterior mediastinal disease: a multi-institutional study.

Anterior mediastinal procedures are increasingly being performed using robot-assisted thoracic surgery (RATS) or video-assisted thoracoscopic surgery (VATS). While both approaches have shown superior outcomes compared to open surgery, their comparative benefits are not as distinct. The aim of this retrospective study was to bridge this knowledge gap using a multicenter dataset. Patients who underwent elective minimally invasive surgery for anterior mediastinal disease between 2015 and 2022 were deemed eligible. The study participants were grouped based on whether a robot was used or not, and perioperative outcomes were compared. To mitigate selection bias, inverse probability of treatment weighting (ITPW) was applied using the propensity score. The final analysis included 312 patients (RATS = 120; VATS = 192). Following the application of IPTW, RATS was found to be associated with a longer operating time (215.3 versus 139.31 min, P < 0.001), fewer days with a chest tube (1.96 versus 2.61 days, P = 0.047), and a shorter hospital stay (3.03 versus 3.91 days, P = 0.041) compared to VATS. Subgroup analyses indicated that the benefit of RATS in reducing the length of hospital stay was particularly pronounced in patients with tumors larger than 6 cm (mean difference [MD] = - 2.28 days, P = 0.033), those diagnosed with myasthenia gravis (MD = - 3.84 days, P = 0.002), and those who underwent a trans-subxiphoid surgical approach (MD = - 0.81 days, P = 0.04). Both VATS and RATS are safe and effective approaches for treating anterior mediastinal disease. However, RATS holds distinct advantages over VATS including shorter hospital stays and reduced chest tube drainage periods.

Thymoma negatively affects the neurological outcome of myasthenia gravis after thymectomy: a propensity score matching study.

BACKGROUND: Thymoma and myasthenia gravis (MG) interact with each other. This study aimed to evaluate the effects of thymoma on neurological outcome of MG patients after thymectomy using the propensity score matching (PSM) method. METHODS: Consecutive patients with MG who underwent thymectomy at Beijing Hospital between January 2012 and August 2021 were retrospectively enrolled. Clinical and follow-up data were collected. Statistical analysis was performed using SPSS 23.0 software. PSM was performed to eliminate selection bias. RESULTS: A total of 456 patients were included in this study. Thymoma was present in 138 (30.3%) patients. The median follow-up time was 72 (range, 12-135) months. At the last follow-up, a lower proportion of thymomatous MG patients achieved complete stable remission (CSR) compared with non-thymomatous MG patients (P = 0.011), and the effective rate [CSR + pharmatologic remission (PR) + minimal manifestations (MM)] of thymomatous MG patients was also lower (P = 0.037). Considering time to CSR, Kaplan-Meier analysis showed thymomatous MG patients had lower cumulative CSR rate than non-thymomatous MG patients (log-rank, P = 0.019). After PSM, 105 pairs of patients were matched successfully. For the matched patients, thymomatous MG patients had a lower CSR rate and a lower effective rate (P = 0.002, 0.039, respectively), and K-M analysis still showed thymomatous MG patients had lower cumulative CSR rate (log-rank, P = 0.048). Multivariate Cox analysis demonstrated that thymoma (HR: 0.592, 95% CI 0.389-0.900, P = 0.014), older age at the time of surgery (HR: 0.971, 95% CI 0.953-0.990, P = 0.003), and preoperative course of MG > 12 months (HR: 0.474, 95% CI 0.317-0.708, P = 0.000) were negative predictive factors for CSR. CONCLUSIONS: Thymoma had a negative effect on the neurological outcome of MG after thymectomy. MG patients with old age and a preoperative course of longer than one year had a lower probability of achieving CSR.

A Rare Case of Metaplastic Thymoma Presenting With Myasthenia Gravis.

Thymomas are tumors of the mediastinum often associated with autoimmune conditions, in particular myasthenia gravis. In contrast, among the fewer than 40 reports of metaplastic thymoma, myasthenia gravis is rarely found. We describe the fourth patient, and first man, with metaplastic thymoma and myasthenia gravis. A 34-year-old had acute onset of double vision with associated dysphagia and was found to have an elevation of serum acetylcholine receptor antibodies. He underwent a transsternal thymectomy. Tissue sections showed a biphasic proliferation of keratin-positive epithelial cells with a complement of spindle cells confirming the diagnosis of metaplastic thymoma. Terminal deoxynucleotidyl transferase (TDT)-positive T lymphocytes were rare and only found in the periphery of the tumor, consistent with thymic remnant. A YAP1::MAML2 gene fusion, with an in-frame fusion between genes YAP1 Exon5 (NM_001130145) and MAML2 Exon2 (NM_032427) was found, supporting further the diagnosis of metaplastic thymoma (Anchored multiplex RNA sequencing [Archer Dx, Boulder, CO] assay). The patient's gender and relatively young age, the presence of an autoimmune condition, and the lack of lymphocytic infiltrate all contribute unusual features to this case and suggest avenues for further exploration.

Germinal centers are associated with postthymectomy myasthenia gravis in patients with thymoma.

BACKGROUND AND PURPOSE: Germinal centers (GCs) can be observed in the thymic tissues of patients with thymoma-associated myasthenia gravis (MG). Although an association between thymic GCs and MG has been suggested, it is unknown whether the presence of GCs could predict the development of MG after the resection of thymoma, known as postthymectomy MG. METHODS: We conducted a retrospective analysis of previously nonmyasthenic patients who underwent surgical removal of the thymoma. All available thymic tissue slides were rereviewed by a pathologist to assess for GCs. Patients were classified into GC-positive and GC-negative groups based on the presence of GCs. The incidence of postthymectomy MG was compared between the two groups, and the risk factors for postthymectomy MG were assessed. RESULTS: Of the 196 previously nonmyasthenic patients who underwent thymoma resection, 21 were GC-positive, whereas 175 were GC-negative. Postthymectomy MG developed in 11 (5.6%) patients and showed a higher incidence in the GC-positive group than in the GC-negative group (33.3% vs. 2.3%, p < 0.001). No postoperative radiotherapy and the presence of GCs were risk factors for postthymectomy MG in the univariate analysis. In multivariate analysis, invasive thymoma (hazard ratio [HR] = 9.835, 95% confidence interval [CI] = 1.358-105.372), postoperative radiotherapy (HR = 0.160, 95% CI = 0.029-0.893), and presence of GCs (HR = 15.834, 95% CI = 3.742-67.000) were significantly associated with postthymectomy MG. CONCLUSIONS: Thymic GCs may be a significant risk factor for postthymectomy MG. Even in patients with thymoma who do not show clinical symptoms of MG, postthymectomy MG should be considered, especially if thymic GCs are observed.

The Clinical Course and Treatment of a Case of Refractory Systemic Juvenile Myasthenia Gravis Successfully Treated with Thymectomy.

Juvenile myasthenia gravis (JMG) exhibits a more favorable response to glucocorticoids and has a better prognosis than adult myasthenia gravis. However, no established treatment exists for refractory JMG. Although thymectomy has been performed in several patients with refractory systemic JMG, there are few detailed clinical descriptions of patients who underwent thymectomy. Here, we present the case of a 10-year-old boy with refractory systemic JMG who was successfully treated with thymectomy. The patient developed symptoms, including dysphagia, malaise, diurnal ptosis, and weakness in the trunk muscles, and he was diagnosed with generalized JMG. Despite undergoing various treatments, including steroids, tacrolimus, steroid pulse therapy, intravenous immunoglobulin, azathioprine (AZT), and rituximab, his symptoms did not improve. Therefore, he underwent a thoracoscopic thymectomy 24 months after disease onset. Thymectomy led to remission, as demonstrated by a significant reduction in the quantitative myasthenia gravis score and anti-acetylcholine receptor antibody levels, which persisted for 43 months after surgery. Our case demonstrates the effectiveness of thymectomy in systemic JMG patients with positive anti-acetylcholine receptor antibodies, despite therapeutic failure with AZT and rituximab, within 2 years of disease onset.

Association between systemic lupus erythematosus and myasthenia gravis: A population-based National Study.

BACKGROUND: Systemic lupus erythematosus (SLE) and myasthenia gravis (MG) are autoimmune diseases. Previous case reports and case series suggest an association may exist between these diseases, as well as an increased risk of SLE after thymectomy for MG. We undertook this study to determine whether SLE and MG were associated in large cohorts. METHODS: We searched the IBM Watson Health Explorys platform and the Department of Veterans Affairs Million Veteran Program (MVP) database for diagnoses of SLE and MG. In addition, we examined subjects enrolled in the Lupus Family Registry and Repository (LFRR) as well as controls for a diagnosis of MG. RESULTS: Among 59,780,210 individuals captured in Explorys, there were 25,750 with MG and 65,370 with SLE. 370 subjects had both. Those with MG were >10 times more likely to have SLE than those without MG. Those with both diseases were more likely to be women, African American, and at a younger age than MG subjects without SLE. In addition, the MG patients who underwent thymectomy had an increased risk of SLE compared to MG patients who had not undergone thymectomy (OR 3.11, 95% CI: 2.12 to 4.55). Autoimmune diseases such as pernicious anemia and miscellaneous comorbidities such as chronic kidney disease were significantly more common in MG patients who developed SLE. In the MVP, SLE and MG were also significantly associated. Association of SLE and MG in a large SLE cohort with rigorous SLE classification confirmed the association of SLE with MG at a similar level. CONCLUSION: While the number of patients with both MG and SLE is small, SLE and MG are strongly associated together in very large databases and a large SLE cohort.

Early life thymectomy induces arterial dysfunction in mice.

Aging of the arteries is characterized by increased large artery stiffness and impaired endothelium-dependent dilation. We have previously shown that in old (22-24 month) mice T cells accumulate within aorta and mesentery. We have also shown that pharmacologic and genetic deletion of these T cells ameliorates age-related arterial dysfunction. These data indicate that T cells contribute to arterial aging; however, it is unknown if aged T cells alone can induce arterial dysfunction in otherwise young mice. To produce an aged-like T cell phenotype, mice were thymectomized at three-weeks of age or were left with their thymus intact. At 9 months of age, thymectomized mice exhibited greater proportions of both CD4 + and CD8 + memory T cells compared to controls in the blood. Similar changes were observed in the T cells accumulating in the aorta and mesentery. We also observed greater numbers of proinflammatory cytokine producing T cells in the aorta and mesentery. The phenotypic T cell changes in the blood, aorta and mesentery of thymectomized mice were similar to those observed when we compared young (4-6 month) to old thymus intact mice. Along with these alterations, compared to controls, thymectomized mice exhibited augmented large artery stiffness and greater aortic collagen deposition as well as impaired mesenteric artery endothelium dependent dilation due to blunted nitric oxide bioavailability. These results indicate that early life thymectomy results in arterial dysfunction and suggest that an aged-like T cell phenotype alone is sufficient to induce arterial dysfunction in otherwise young mice.

Unexpected fibrous mediastinitis in a patient with myasthenia gravis - a case report.

BACKGROUND: Fibrous mediastinitis (FM) is a rare mediastinal lesion characterized by proliferation of fibrous tissue within the mediastinum. Previous reports have shown that this lesion can be caused by histoplasmosis and tuberculosis. In extremely rare cases, FM can also be caused by autoimmune diseases such as antineutrophil cytoplasmic antibody-associated vasculitis and large-vessel arteritis. CASE PRESENTATION: In our case, we report unexpected fibrous mediastinitis found after robotic thymectomy in a patient with myasthenia gravis (MG). The preoperative imaging indicated no obvious lesion in the mediastinum and the patient denied histories of both histoplasmosis and tuberculosis. After the operation, both proliferation of fibrous tissue and ectopic germinal centres (GCs) could be found in the thymus. CONCLUSION: This rare case might enrich our knowledge of the relationship between FM and autoimmune diseases.