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Endocrine-related Cancer Jul 2021Intrathyroidal thymic carcinoma (ITC) is a rare thyroid tumor that resembles thymic carcinoma, for which there are no recommendations on diagnostic and therapeutic... (Meta-Analysis)
Meta-Analysis
Intrathyroidal thymic carcinoma (ITC) is a rare thyroid tumor that resembles thymic carcinoma, for which there are no recommendations on diagnostic and therapeutic approaches. We performed a pooled analysis of published ITC cases to describe the natural history of this disease and identify prognostic factors. We performed a systematic review of histopathological-confirmed ITC cases published in the literature in English. The following keywords were used: 'intrathyroidal thymic carcinoma', 'carcinoma showing thymus-like differentiation', 'CASTLE tumor', 'thyroid carcinoma showing thymus like differentiation'. Fifty eligible publications were identified, providing data from 132 patients, plus a case diagnosed at our institution. Median disease-free survival (DFS) of this patient series was 144 months (range 91-197), while median overall survival (OS) was not reached. Upfront surgery was performed in 97% of patients and 24% of them experienced disease recurrence after a median of 19 months (range 13-25). Complaining of major symptoms, as a sign of more advanced local stage, was the only prognostic factor significantly associated with a higher risk of death at multivariate analysis (HR 4.903, 95% CI: 1.092-22.008, P = 0.038). Postoperative radiation therapy was not associated with prognosis, while not enough data were available to assess the efficacy of chemotherapy. ITC is a rather indolent disease and ITC patients have a relatively good prognosis. Surgery is the mainstay of therapy. Survival outcome of patients depends on tumor burden and complete surgical resection. Postoperative radiation effect seems to be negligible. Data on the efficacy of chemotherapy in advanced patients are lacking.
Topics: Carcinoma; Humans; Neoplasm Recurrence, Local; Prognosis; Retrospective Studies; Thymoma; Thymus Neoplasms; Thyroid Neoplasms
PubMed: 34105516
DOI: 10.1530/ERC-21-0123 -
Lung Cancer (Amsterdam, Netherlands) Jul 2021Pure red cell aplasia (PRCA) is a rare paraneoplastic syndrome observed in 2-5 % of thymomas. Literature reports great variability in its management. Based on an... (Review)
Review
Pure red cell aplasia (PRCA) is a rare paraneoplastic syndrome observed in 2-5 % of thymomas. Literature reports great variability in its management. Based on an illustrative clinical case, we present a systematic literature review whose main objective is to evaluate the therapeutic management of PRCA. The literature search was performed based on the PICO method in the Medline and Scopus databases. The reference clinical case concerns a 51-year-old woman with stage IVa thymoma. After initial response to chemotherapy, a locoregional progression occurred with PRCA development that responded favorably under second line chemotherapy. The patient finally died in a context of bicytopenia with febrile neutropenia. The systematic review covers 135 articles published between 1950 and 2019. Thymectomy alone or in combination with other therapies showed a 31 % complete remission (CR) rate for PRCA of, whereas none was reported with anti-tumor treatments without thymectomy. Among immunomodulatory therapies, cyclosporin gave the highest percentage of CR (74 %). Finally, the combination of thymectomy and immunomodulatory treatments showed a CR rate of 45 %. Thymectomy appeared to be the most effective anti-tumor treatment for PRCA. Immunomodulatory therapies, particularly cyclosporine, are shown effective, but the risk of infectious complications must be considered. The optimal place of anti-tumor and immunomodulatory therapies against PRCA has yet to be determined.
Topics: Female; Humans; Lung Neoplasms; Middle Aged; Red-Cell Aplasia, Pure; Thymectomy; Thymoma; Thymus Neoplasms
PubMed: 34049719
DOI: 10.1016/j.lungcan.2021.05.010 -
Reviews in Endocrine & Metabolic... Dec 2021Knowledge of ectopic Cushing's syndrome (CS) due to thymic neuroendocrine tumours (NETs) comes from short series or single cases. Our aim is to perform a systematic... (Review)
Review
Knowledge of ectopic Cushing's syndrome (CS) due to thymic neuroendocrine tumours (NETs) comes from short series or single cases. Our aim is to perform a systematic review using PubMed, Embase, Scopus, Ovid Medline and Biosis Previews of all cases with ectopic CS due to thymic NETs reported in the last 40 years and describe one illustrative patient attended in our institution. Search of literature: From 162 patients, 58.6% were male and mean age was 34.6 ± 13.9 years-old. Median of symptoms until diagnosis was 6 [2-24] months and 62% had aggressive CS. Imaging was positive in 93.7% (chest X-ray), 97.8% (computed tomography), 80.7% (somatostatin receptor scintigraphy) and median tumour size was 47 [25-68.5] mm. At presentation, 18% had localized disease, 26.2% locally invasive and 55.7% advanced. Eighty-eight present underwent surgery and histological subtypes were atypical (46.7%), typical (30.4%) and carcinoma (21.7%). Tumour persisted or recurred in 70.1%, 63% received radiotherapy and 45.2% chemotherapy. Follow-up median was 26.6 [14.5-57.5] months and mortality was reported in 35.8% with median survival of 38 [19-60] months. MEN-1 mutation was referred in 3.1%. Comparatively, carcinomas had aggressive CS more frequently while atypical showed advanced disease more often. In conclusion, thymic NETs causing ectopic CS are presented as aggressive hypercortisolism in the middle aged population. The disease is commonly extended at diagnosis and persists or recurs after surgery in most patients with a short term high mortality.
Topics: ACTH Syndrome, Ectopic; Adult; Cushing Syndrome; Humans; Male; Middle Aged; Neuroendocrine Tumors; Thymoma; Thymus Neoplasms; Young Adult
PubMed: 33961211
DOI: 10.1007/s11154-021-09660-2 -
Journal of Thoracic Oncology : Official... Apr 2021Our systematic review and meta-analysis aimed to evaluate the effect of postoperative radiotherapy (PORT) on completely resected Masaoka/Masaoka-Koga (M/MK) stage II/III... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Our systematic review and meta-analysis aimed to evaluate the effect of postoperative radiotherapy (PORT) on completely resected Masaoka/Masaoka-Koga (M/MK) stage II/III thymomas.
METHODS
We systematically searched four online databases and included studies that compared surgery alone versus surgery plus a PORT for completely resected M/MK stage II/III thymoma. The multivariate-adjusted hazard ratios (HRs) of overall survival (OS) and disease-free survival were evaluated as the primary and secondary end points, respectively. We performed a subgroup analysis for OS with respect to M/MK stage II, III, and inseparable II/III cases. A generic inverse variance meta-analysis using a random model was conducted.
RESULTS
Five studies including 4746 patients (among them, 2408 patients received PORT) met our selection criteria. A meta-analysis of these five studies revealed that PORT was associated with a significantly better OS (HR = 0.68, 95% confidence interval [CI]: 0.57-0.83, p < 0.001, I = 0%, p for heterogeneity = 0.97). Subgroup analyses for M/MK stage II disease (HR = 0.63, 95% CI: 0.44-0.91, p = 0.01, I = 0%, p for heterogeneity = 0.80) and M/MK stage III disease (HR = 0.72, 95% CI: 0.55-0.95, p = 0.02, I = 0%, p for heterogeneity = 0.84) revealed similar results. PORT was not associated with an improved disease-free survival (HR = 0.96, 95% CI: 0.70-1.33, p = 0.83, I = 0%, p for heterogeneity = 0.72).
CONCLUSIONS
Currently available evidence from observational studies suggests PORT for patients with completely resected M/MK stage II/III thymoma. A randomized trial is warranted.
Topics: Disease-Free Survival; Humans; Lung Neoplasms; Neoplasm Staging; Radiotherapy, Adjuvant; Retrospective Studies; Thymoma; Thymus Neoplasms
PubMed: 33515812
DOI: 10.1016/j.jtho.2020.12.023 -
BMJ Case Reports Dec 2020Nocardiosis is a rare infection in patients with myasthenia gravis (MG). We identified three cases of MG admitted with nocardiosis in our unit. We performed systematic...
Nocardiosis is a rare infection in patients with myasthenia gravis (MG). We identified three cases of MG admitted with nocardiosis in our unit. We performed systematic literature search of previous publications and identified 18 patients. This paper presents three patients and reviews the clinical characteristics of 21 patients. The first case was a 69-year-old woman with thymomatous MG who presented with pustules and left lower limb pain. Evaluation showed osteomyelitis of the pubic ramus and ileopsoas abscess. The second case was a 54-year-old man who presented in myasthenic crisis due to pulmonary nocardiosis. The third case was a 48-year-old man with thymomatous MG who presented with lung abscess. All of them recovered completely after treatment with co-trimoxazole. Analysis of the 21 patients identified four risk factors for nocardiosis in MG: elderly men; thymoma; immunosuppressant medication, mainly steroid therapy; and pre-existing lung disease. Lungs was the most common site of infection. Suppurative disease was common manifestation regardless of organ involved. Clinical course is not unfavourable.
Topics: Aged; Anti-Bacterial Agents; Female; Humans; Male; Middle Aged; Myasthenia Gravis; Nocardia Infections; Rare Diseases; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination
PubMed: 33384345
DOI: 10.1136/bcr-2020-237208 -
Cancer Treatment Reviews Jan 2021Primary enteric adenocarcinoma of the thymus (EAT) is a recently proposed rare subtype of thymic carcinoma. Unlike thymic carcinomas with squamous histology, for which...
BACKGROUND
Primary enteric adenocarcinoma of the thymus (EAT) is a recently proposed rare subtype of thymic carcinoma. Unlike thymic carcinomas with squamous histology, for which clinical guidelines are available, little knowledge is available regarding the clinical and pathological features of EAT, and there is no consensus on the best treatment algorithm for such tumors.
METHODS
We performed a systematic review of the literature, searching for all cases of EAT reported. We also retrospectively reviewed all cases of EAT treated at the European Institute of Oncology (IEO) between January 2000 and January 2020. Individual patient data were extracted and analyzed in order to delineate clinical and pathological features, as well as patients' prognosis and treatments outcome, evaluated in terms of Disease free Survival (DFS), Progression free survival (PFS) and overall survival (OS).
RESULTS
Thirty-three cases (29 reported in literature and 4 new cases treated at IEO) of thymic adenocarcinoma deploying enteric differentiation as defined by WHO-criteria were analyzed. All tumors showed positive immunoreactivity for cytokeratin (CK) 20 and/or caudal type homeobox 2 (CDX2). Data on molecular profiling by next-generation sequencing were available in only 3 cases, and did not show actionable findings. At diagnosis, 11 pts had an early-stage (Masaoka I-II) and 22 a locally advanced (10 pts) or metastatic (12 pts) disease. Median-DFS of patients with localized disease was 12 months (95% CI, 7-19). Patients who received systemic chemotherapy were mostly treated with regimens commonly used for thymic epithelial tumors, with a discouraging PFS of 3-5 months for patients with stage IV disease. Median OS of the whole population was 34 months (95% CI, 24-NA:. mOS was not reached for patients with stage I-II disease versus 34 months in stage III-IV (p < 0.05).
CONCLUSION
Available evidence suggests that EAT represents a distinct entity in the context of thymic epithelial tumors, characterized by aggressive clinical behavior, poor responsiveness to chemotherapy and dismal patients prognosis. More research is needed to better define optimal management strategies for patients with such rare disease.
Topics: Adenocarcinoma; Adolescent; Adult; Aged; Female; Humans; Male; Middle Aged; Progression-Free Survival; Retrospective Studies; Thymoma; Treatment Outcome; Young Adult
PubMed: 33296826
DOI: 10.1016/j.ctrv.2020.102133 -
Journal of Neurology Dec 2021Corticosteroids (CS) are among the most widely- used immunosuppressive agents for immune-mediated conditions, including myasthenia gravis (MG). While their effectiveness... (Review)
Review
Corticosteroids (CS) are among the most widely- used immunosuppressive agents for immune-mediated conditions, including myasthenia gravis (MG). While their effectiveness in MG is documented and supported in the clinical practice over several decades, one of the main drawbacks of treatment results from the notion that MG patients may experience symptom worsening following CS treatment initiation. This may lead to the administration of lower than necessary doses of CS for the disorder, or even avoiding them altogether. As a consequence, some patients may not receive the optimal treatment to control their disease. In the present review, we analyzed 27 relevant publications and determined the prevalence of clinical exacerbation following CS treatment, its' severity and relation to the type and dose of CS. The rate of MG exacerbation is highest with the administration of cortisone, intermediate with prednisone, and lowest with methylprednisolone. High dose daily or alternate-day prednisone is associated with exacerbation more frequently than low-dose treatment, but most exacerbations are of mild to moderate severity. Other factors related to increased risk of an initial exacerbation include older age, generalized MG, bulbar symptoms, disease severity, presence of thymoma, and thymectomy. However, the current information is based mostly on heterogeneous studies of low quality, and prospective clinical trials designed to compare between the various agents and doses and assess the rate and severity of the exacerbation by a unified scale are warranted.
Topics: Adrenal Cortex Hormones; Aged; Humans; Myasthenia Gravis; Prospective Studies; Thymectomy; Thymus Neoplasms
PubMed: 33064188
DOI: 10.1007/s00415-020-10264-0 -
Journal of Cardiothoracic Surgery Sep 2020Despite the burgeoning literature describing preoperative and postoperative risks of a myasthenic crisis after thymectomy (MCAT) in patients with myasthenia gravis,... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Despite the burgeoning literature describing preoperative and postoperative risks of a myasthenic crisis after thymectomy (MCAT) in patients with myasthenia gravis, substantial differences exist in the risk factors identified by previous studies. We conducted a meta-analysis to assess the reported risk factors and MCAT risk.
METHODS
We collected relevant studies on the risk factors for MCAT by searching the PubMed, Embase, The Cochrane Library, China Biology Medicine (CBM), WanFang Data, VIP and CNKI databases. The search period ranged from the establishment of the database to November 2019.
RESULTS
Twenty-five of the 458 identified studies were eligible for the meta-analysis. Seven retrospective cohort studies and 18 case-control studies were included, and 14 risk factors for MCAT were extracted. Meta-analyses of the association between MCAT and risk factors related to the patient's preoperative condition included a preoperative history of MC, preoperative bulbar symptoms, IIa + IIb + III + VI, IIb + III + VI, VI + V, dosage of pyridostigmine bromide prior to the operation, a preoperative AchR-Ab level > 100 (nm/L), preoperative pulmonary function, preoperative complications, and preoperative disease course. Meta-analyses of the association between MCAT and surgery-related risk factors included intraoperative blood loss > 1000 mL and the mode of operation. Meta-analyses of the association between MCAT and postoperative risk factors included postoperative lung infection, thymoma and the WHO classification. The operation time was not an independent risk factor for MCAT.
CONCLUSIONS
The independent risk factors for MCAT were a preoperative history of MC, preoperative bulbar symptoms, preoperative MG Osserman stage, preoperative dosage of pyridostigmine bromide, preoperative serum AchR-Ab level, lung function, major postoperative complications, disease duration before thymectomy, blood loss, thoracotomy, postoperative lung infection, thymoma, and WHO classification.
Topics: Blood Loss, Surgical; Databases, Factual; Female; Humans; Male; Myasthenia Gravis; Operative Time; Postoperative Complications; Risk Factors; Thymectomy
PubMed: 32993739
DOI: 10.1186/s13019-020-01320-x -
Medicine Jun 2020The pathogenesis of myasthenia gravis (MG) has strong connection with thymic abnormalities. Thymic hyperplasia or thymoma can be found with most patients. Thymectomy is... (Comparative Study)
Comparative Study
Effectiveness and safety of thymectomy plus prednisone compares with prednisone monotherapy for the treatment of non-thymomatous Myasthenia Gravis: Protocol for a systematic review.
BACKGROUND
The pathogenesis of myasthenia gravis (MG) has strong connection with thymic abnormalities. Thymic hyperplasia or thymoma can be found with most patients. Thymectomy is currently one of the regular treatment in clinic, which is, however, still controversial for non-thymomatous MG. This research will assess the effectiveness and safety of thymectomy plus prednisone compared to prednisone monotherapy for the treatment of non-thymomatous MG systematically.
METHODS
According to eligibility and ineligibility criteria, 8 databases, including PubMed, EMBASE, the Web of Science, the Cochrane Library, China National Knowledge Infrastructure (CNKI), Wan-fang Database, Chinese Biomedical Literature Database (CBM), China Science and Technology Journal Database (CSTJ), will be searched to gather the up-to-standard articles from September 2000 to September 2025. Inclusion criteria are as follows: randomized controlled trials of thymectomy plus prednisone for the treatment of non-thymomatous MG. The quantitative myasthenia gravis score (QMG) and the dose of prednisone required will be accepted as the main outcomes. Data synthesis, subgroup analysis, sensitivity analysis, and meta-regression analysis will be conducted using RevMan 5.3 software. We will use Egger or Begg test to evaluate symmetry on a funnel plot which is made to assess reporting bias, and use trial sequential analysis (TSA) to exclude the probability of false positives.
RESULTS
This systematic review will measure the QMG and the dose of prednisone required, the myasthenia gravis activities of daily living scale scores (MG-ADL), treatment-associated complications, incidence of myasthenic crisis and other aspects to comprehensively assess the clinical benefits of thymectomy plus prednisone for MG patients without thymoma.
CONCLUSION
The conclusion of this study will achieve convincing evidence to evaluate the effectiveness and safety of thymectomy plus prednisone for the treatment of non-thymomatous MG.
PROSPERO REGISTRATION NUMBER
CRD 42020167735.
Topics: Anti-Inflammatory Agents; Combined Modality Therapy; Humans; Myasthenia Gravis; Prednisone; Thymectomy; Treatment Outcome
PubMed: 32569233
DOI: 10.1097/MD.0000000000020832 -
Current Opinion in Neurology Jun 2020To systematically review the clinical features, diagnosis, and management of anti-gamma-aminobutyric acid receptor Type A (GABAA) autoimmune encephalitis with a focus on...
PURPOSE OF REVIEW
To systematically review the clinical features, diagnosis, and management of anti-gamma-aminobutyric acid receptor Type A (GABAA) autoimmune encephalitis with a focus on recent data.
RECENT FINDINGS
In a review of published reports, we identified 50 cases of anti-GABAA receptor encephalitis with clinical features reported. The median age at presentation was 47 years old (range, 2.5 months-88 years old), 64% were adults, 36% were children and it occurred in both males and females. Eight-two percent (41/50) presented with seizures, 72% (36/50) with encephalopathy, and 58% (29/50) with both. Of those presenting with seizures, 42% developed status epilepticus during their disease course. Ninety-six percent (48/50) had MRI results reported, with 83% of these cases having abnormal findings, most commonly multifocal/diffuse cortical and subcortical T2/FLAIR hyperintense lesions without associated gadolinium enhancement. Almost one-third, 28% (14/50), had an associated malignancy detected by the time of diagnosis, 64% (9/14) of which was thymoma. Of 44 patients with outcomes reported, 80% had partial or complete recovery, whereas 20% had poor outcomes including 11% (5/44) who died. Of the 42 patients with type of treatment(s) and outcomes reported, 54% (23/42) received only first-line immunotherapy and 31% (13/42) received first-line and second-line immunotherapy. Receiving a combination of first-line and second-line immunotherapy may be associated with higher likelihood of complete recovery. When follow-up MRIs were reported, all showed improvement, and sometimes complete resolution, of T2/FLAIR hyperintensities.
SUMMARY
Anti-GABAA receptor encephalitis can present across the age spectrum and should be considered in patients who present with rapidly progressive encephalopathy and/or seizures. Brain MRI often shows a distinctive pattern of multifocal cortical and subcortical T2/FLAIR hyperintense lesions, generally not typical of other known central nervous system autoantibody associated encephalitis syndromes. High clinical suspicion and early diagnosis are important given the potential for clinical improvement with immunotherapy.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Autoantibodies; Child; Child, Preschool; Encephalitis; Female; Hashimoto Disease; Humans; Immunotherapy; Infant; Magnetic Resonance Imaging; Male; Middle Aged; Receptors, GABA-A; Seizures; Young Adult
PubMed: 32374573
DOI: 10.1097/WCO.0000000000000814