Search

Open in new tab Download slide OBJECTIVES Total thymectomy in addition to medical treatment is an accepted standard therapy for myasthenia gravis (MG). Patients with severe generalized MG present life-threatening events, poor prognosis and higher risk of postoperative myasthenic crisis. The aim of our study is to investigate neurological and surgical results in patients with Myasthenia Gravis Foundation of America (MGFA) class IV and V MG following thymectomy. METHODS Data on 76 MG patients with preoperative MGFA classes IV and V who underwent thymectomy were retrospectively collected. Primary end points included short-term surgical outcomes and long-term neurological results including the achievement of complete stable remission and any improvement as defined by MGFA Post-Intervention Status criteria. RESULTS There were 27 (35.5%) males and 49 (64.5%) females; 53 (69.7%) were classified as MGFA class IV and 23 (30.3%) as class V. Thymectomy was performed through sternotomy in 25 (32.9%) patients, Video-assisted thoracic surgery (VATS) in 5 (6.6%) and Robot-assisted thoracic surgery (RATS) in 46 (60.5%). The median operative time was 120 (interquartile range: 95; 148) min. In-hospital mortality was observed in 1 (1.3%) patient and postoperative complications in 14 (18.4%) patients. The median postoperative hospital stay was 4 (interquartile range: 3; 6) days. Pathological examination revealed 31 (40.8%) thymic hyperplasia/other benign and 45 (59.2%) thymomas. Cumulative complete stable remission and improvement probabilities were 20.6% and 83.7% at 5 years and 66.9% and 97.6% at 10 years, respectively. A significant improvement rate was found in patients with age at the time of thymectomy of ≤50 years (P  = 0.0236), MGFA class V (P  = 0.0154) and acetylcholine receptor antibodies positivity (P  = 0.0152). CONCLUSIONS Thymectomy in patients with severe MG yields good perioperative outcomes and satisfactory long-term neurological improvement, especially for patients younger than 50 years, with MGFA class V and anti-AChR+ MG. [ABSTRACT FROM AUTHOR]

Open in new tab Download slide Open in new tab Download slide OBJECTIVES The goal of this study was to analyse the outcomes in 53 patients with thymoma, 34 of whom had myasthenia gravis (MG), who were treated with robotic surgery. The oncological outcomes of the whole series of patients were analysed. Furthermore, because consistent data are not yet available in the literature, the main focus was the analysis of the neurological results of the patients affected by MG and thymoma. METHODS The clinical outcomes of 53 patients with a diagnosis of thymoma who underwent robotic thymectomy between January 2014 and December 2019 in our institution were collected and evaluated; 34 of these patients had a concomitant diagnosis of MG. The neurological status of the patients was determined from a clinical evaluation according to the Osserman classification and on pre- and post-surgery Myasthenia Gravis Composite scores, whereas neurological clinical outcomes were assessed using the Myasthenia Gravis Foundation of America Post-Intervention Score. Reduction of steroid therapy was also considered. The recurrence rate, adjuvant radiotherapy and overall survival of the patients with a thymoma were evaluated. RESULTS Neurological outcomes: improvement of the clinical conditions was obtained in 26 patients (76.5%) following the operation: complete stable remission was observed in 5 patients (14.7%), pharmacological remission in 10 (29.4%) and minimal manifestation in 11 (32.3%). Four patients (11.8%) exhibited no substantial change from the pretreatment clinical manifestations or reduction in MG medication and 4 (11.8%) patients experienced worsening of clinical conditions. In 21 patients (61.7%) a reduction of the dosage of steroid therapy was obtained. Oncological outcomes: at an average follow-up of 36 months, the overall survival was 96%, 4 patients (7.5%) had pleural relapses and 12 patients (22.6%) underwent postoperative radiotherapy, according to their stage. In accordance with Masaoka staging, 34% were in stage I, 56.6% in stage II and 9.4% in stage III CONCLUSIONS Our results suggest that robotic surgical treatment of patients with thymoma and concomitant MG is effective in improving the neurological outcomes. Moreover, the oncological results obtained in this series confirm the efficacy of robotic surgery for the treatment of thymic malignancies, with results in line with those of open surgery. However, due to the indolent growth of thymomas, further observations with longer follow-up are necessary. [ABSTRACT FROM AUTHOR]

Background: Thymoma‐associated myasthenia gravis (TAMG) is one of the subtypes of myasthenia gravis with autoantibodies against the acetylcholine receptor (AChR‐Ab). We analyzed the clinical features of our cohort of TAMG patients and the changes in AChR‐Ab titer before and after thymectomy in order to identify factors predicting thymoma relapses. Methods: We retrospectively assessed: age of MG onset, MG clinical status according to MGFA (Myasthenia Gravis Foundation of America), epoch of thymectomy, post‐thymectomy status, oncological features and surgical approach. AChR‐Ab dosages were measured both before and after thymectomy. Linear regression models were applied to identify clinical determinants of AChR‐Ab titers and the Cox regression model was fitted to estimate the factors associated with the risk of thymoma recurrence. Results: The study sample included 239 MG patients, 27 of whom experienced one or more recurrences (median follow‐up time: 4.8 years). The AChR‐Ab titers decreased after first thymectomy (P < 0.001); the decrease was more pronounced in female patients (P = 0.05), in patients diagnosed with MG at an older age (P = 0.003), and in those who had lower MG stage before surgery (P = 0.02) or higher Masaoka‐Koga stage (P = 0.005). The risk of relapse was closely linked with the age of the patient, the Masaoka‐Koga stage and the surgical approach. Conclusions: Presurgery levels of AChR‐Ab or their change after surgery were not associated with thymoma recurrence. The reduction of AChR‐Ab titers after thymectomy confirms an immunological role of thymoma in the pathogenesis of MG. Key points: Significant findings of the study: Young MG patients with an advanced Masaoka staging score of the primary tumor who underwent thymectomy with approaches different from sternotomy and VATS should be monitored for high risk of recurrence.What this study adds: No other study has ever investigated the changes in AChR‐Ab titers before and after thymectomy in a large cohort of TAMG patients. The reduction of AChR‐Ab titers after thymectomy suggests an immunological role of thymoma in the pathogenesis of MG. [ABSTRACT FROM AUTHOR]

Background Myasthenia Gravis (MG) is caused, in approximately 80% of the patients, by autoantibodies against the nicotinic acetylcholine receptor (AChR). The disease is often associated with pathological changes of the thymus: thymic epithelial tumours are present in about 10–20% of the patients, while up to 80% of the patients with early disease onset have thymic hyperplasia. Folate metabolism is required for the production of DNA precursors and for proper DNA methylation reactions, and impaired folate metabolism has been often associated with cellular growth and cancer. Methods We investigated if major polymorphisms of folate-related genes, namely MTHFR c.677C > T, MTR c.2756A > G, MTRR c.66A > G and TYMS TSER (a 28-bp tandem repeat in the 5′ promoter enhancer region of TYMS) increase the risk of pathological changes of the thymus in AChR + MG patients. A total of 526 AChR + MG patients, including 132 patients with normal (involuted) thymus, 146 patients with thymic hyperplasia, and 248 patients with a thymoma were included in the study. Allele and genotype comparisons were performed among the three study groups, after correcting for multiple testing. Results The frequency of the TYMS TSER 3R allele was significantly higher in MG patients with thymic hyperplasia ( P = 0.004), and the TYMS TSER 3R3R genotype was significantly associated with increased risk of thymic hyperplasia [OR 2.71 (95% CI: 1.34–5.47)]. Conclusions The 3R allele in the thymidylate synthase promoter enhancer region results in increased protein production, required for the synthesis of DNA precursors. The present study suggests that the TYMS TSER 3R allele increases the risk of thymic lymphoid hyperplasia in AChR + MG patients. [ABSTRACT FROM AUTHOR]

• We investigated GHSR methylation levels in thymomas from patients with Myasthenia Gravis. • GHSR hypermethylation was observed in 18 thymomas,28% of the total. • Samples showing GHSR hypermethylation were enriched in advanced disease stages than stage I. • GHSR hypermethylation is not a pan-cancer marker and is infrequent in encapsulated tumors. Hypermethylation of the growth hormone secretagogue receptor gene (GHSR) is increasingly observed in human cancers, suggesting that it could represent a pan-cancer biomarker of clinical interest. However, little is still known concerning GHSR methylation levels in thymic epithelial tumors, and particularly in thymomas from patients with Myasthenia Gravis (TAMG). In the present study we collected DNA samples from circulating lymphocytes and surgically resected tumor tissues of 65 TAMG patients, and from the adjacent healthy thymic tissue available from 43 of them. We then investigated GHSR methylation levels in the collected tissues searching for correlation with the clinical characteristics of the samples. GHSR hypermethylation was observed in 18 thymoma samples (28%) compared to the healthy thymic tissues (P < 1 × 10−4), and those samples were particularly enriched in advanced disease stages than stage I (94% were in stage II or higher). GHSR was demethylated in the remaining 47 thymomas, as well as in all the investigated healthy thymic samples and in circulating lymphocytes. GHSR hypermethylation is not a pan-cancer marker or an early event in TAMG, but occurs in almost 1/4 of them and mainly from stage II onward. Subsequent studies are required to clarify the molecular pathways leading to GHSR hypermethylation in TAMG tissues and their relevance to disease progression. [ABSTRACT FROM AUTHOR]

Introduction Although Myasthenia gravis (MG) is the most common autoimmune disease associated with thymoma, a small proportion of thymomatous patients can suffer from limbic autoimmune encephalitis (LE). LE is usually characterized by rapid progressive short-term memory deficits, psychiatric symptoms, and seizures. Patients can present antibodies against cell surface antigens, including contactin-associated protein-like 2 (CASPR2) and a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR). Our aim was to analyze the EEG findings of these patients to find possible EEG homologies among their patterns. Methods Clinical information was obtained from a retrospective review of medical records and EEG recordings of three patients with thymoma and LE: two with seropositivity for AMPAR antibodies and one for CASPR2 antibodies. Results The first case was a 37 years-old man with a subacute onset of memory loss, confusion, anxiety and behavioral disorders in the setting of an invasive thymoma (type B2-B3). Brain MRI and dosage of acetylcholine receptor antibodies (AChR-Abs) were normal. EEG showed bilateral fronto-temporal spikes together with slow theta and delta activity. Clinical suspicion of a paraneoplastic neurological syndrome associated with thymoma was confirmed by the serological presence of AMPAR-Abs. The second case was a 47 years-old female patient with Myasthenia Gravis (MG) and seropositivity for AChR-Abs, treated for recurrent thymoma (type B2). She presented three episodes of generalized seizures, together with mental disorientation, impairment of recent memory and insomnia. Brain MRI was normal. EEG showed a peculiar pattern, comprising lateralized right fronto-temporal spikes and generalized sharp waves. Serological tests detected the presence of antibodies to CASPR2. The third case was a 52 years-old female patient with thymoma (type B2-B3) who developed confusion, short-term memory loss and psychomotor agitation after thymectomy. Cerebrospinal fluid (CSF) examination showed a mild blood-CSF barrier damage and brain MRI revealed increased T2 signal involving mesio-temporal cortical areas. EEG showed electrical abnormalities in the fronto-temporal regions. Antibodies to the glutamate receptor 1 (GluR1) and GluR3 subunits of AMPAR were detected both in serum and CSF. Conclusion Limbic autoimmune encephalitis should be suspected in patients with invasive thymoma and subacute onset of confusion, memory loss and seizures. In all these three cases EEG showed epileptiform activity, especially in the fronto-temporal regions, together with slow theta and delta activity, without a pathognomonic pattern. Our results strongly emphasize the importance of testing biological samples when a possible autoimmune CNS involvement is suspected. Even if antibody testing remains the cornerstone in the diagnostic pathway, EEG is paramount in the differential diagnosis with similar disorders, in orienting toward limbic encephalopathy, especially when MRI is inconclusive. [ABSTRACT FROM AUTHOR]