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The Journal of Thoracic and... Jul 2020Paraneoplastic syndromes associated with thymomas remain incompletely understood. The objective was to examine the association between surgically resected thymomas and...
OBJECTIVE
Paraneoplastic syndromes associated with thymomas remain incompletely understood. The objective was to examine the association between surgically resected thymomas and paraneoplastic syndromes over the past half century.
METHODS
A primary PubMed/MEDLINE search was used to identify published articles describing paraneoplastic syndromes associated with thymomas from 1960 to 2019. A secondary search identified additional articles referenced in the articles found in the primary search. Kaplan-Meier and log-rank test were used for time-to-event data analyses.
RESULTS
From 407 articles describing 507 patients, 123 different paraneoplastic syndromes were associated with thymoma. The 5 most common paraneoplastic syndromes were myasthenia gravis, pure red cell aplasia, lichen planus, Good syndrome, and limbic encephalitis. Complete or partial resolution of paraneoplastic syndrome symptoms after surgery was noted in 76% of patients, of whom 21% had a relapse or new paraneoplastic syndrome onset after surgery. The most common adjunctive therapy associated with resolution of paraneoplastic syndrome was corticosteroids (30%). For all patients after surgery, thymoma recurrence was observed in 17% of cases, whereas recurrence of paraneoplastic syndrome was observed in 34% of cases, and both were observed in approximately 11% of cases. The 5- and 10-year overall survivals were 78% and 66%, respectively. Improved overall survival was associated with patients who had total resolution from paraneoplastic syndrome.
CONCLUSIONS
A comprehensive assessment of publications over the past half century suggests that a multimodal treatment approach that includes surgical resection of thymomas is able to achieve paraneoplastic syndrome resolution in a majority of patients. Onset of new paraneoplastic syndromes after surgery is associated with the recurrence of the first paraneoplastic syndrome, and resolution of paraneoplastic syndrome is associated with improved overall survival.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Child; Child, Preschool; Female; Humans; Infant; Male; Middle Aged; Neoplasm Recurrence, Local; Paraneoplastic Syndromes; Thymoma; Treatment Outcome; Young Adult
PubMed: 31982129
DOI: 10.1016/j.jtcvs.2019.11.052 -
Journal of Neurology Apr 2020Contactin-associated protein-like 2 (CASPR2) autoantibody disease has a variable clinical phenotype. We present a case report and performed a systematic review of the...
BACKGROUND
Contactin-associated protein-like 2 (CASPR2) autoantibody disease has a variable clinical phenotype. We present a case report and performed a systematic review of the literature to summarize: (1) the clinical phenotype of patients with CASPR2 antibodies, (2) the findings in neurological investigations, and (3) the associated neuroimaging findings.
METHODS
A chart review was performed for the case report. A systematic review of the medical literature was performed from first available to June 13, 2018. Abstracts were screened, and full-text peer-reviewed publications for novel patients with CASPR2 positivity in serum or cerebrospinal fluid (CSF) were included. Selected publications were reviewed, and relevant information was collated. Data were analyzed to determine overall frequency for demographic information, clinical presentations, and investigation findings.
RESULTS
Our patient was a previously healthy 61-year-old male with both serum and CSF CASPR2 antibodies who presented with limbic encephalitis and refractory epilepsy. He was successfully treated with immunosuppression. For our systematic review, we identified 667 patients from 106 studies. Sixty-nine percent were male. Median age was 54 years (IQR 39-65.5). Median disease duration was 12 months (IQR 5.6-20). Reported overall clinical syndromes were: autoimmune encephalitis [69/134 (51.5%)], limbic encephalitis [106/274 (38.7%)], peripheral nerve hyperexcitability [72/191 (37.7%)], Morvan syndrome [57/251 (22.7%)], and cerebellar syndrome [24/163 (14.7%)]. Patients had positive serum [642/642 (100%)] and CSF [87/173 (50.3%)] CASPR2 antibodies. MRI was reported as abnormal in 159/299 patients (53.1%), and the most common abnormalities were encephalitis or T2 hyperintensities in the medial temporal lobes, or hippocampal atrophy, mesial temporal sclerosis, or hippocampal sclerosis. FDG-PET was abnormal in 30/35 patients (85.7%), and the most common abnormality was temporomesial hypometabolism. The most commonly associated condition was myasthenia gravis (38 cases). Thymoma occurred in 76/348 patients (21.8%). Non-thymoma malignancies were uncommon [42/397 (10.6%)].
CONCLUSIONS
Most patients have autoimmune or limbic encephalitis and corresponding abnormalities on neuroimaging. Other presentations include peripheral nerve hyperexcitability or Morvan syndromes, cerebellar syndromes, behavioral and cognitive changes, and more rarely movement disorders. The most commonly associated malignancy was thymoma and suggests a role for thymoma screening in CASPR2-related diseases.
Topics: Adult; Aged; Autoantibodies; Autoimmune Diseases of the Nervous System; Cognitive Dysfunction; Epilepsy; Female; Humans; Limbic Encephalitis; Male; Membrane Proteins; Middle Aged; Nerve Tissue Proteins
PubMed: 31912210
DOI: 10.1007/s00415-019-09686-2 -
Lung Cancer (Amsterdam, Netherlands) Dec 2018Thymic tumours are rare diseases that for most of the cases are cured with surgery and eventually adjuvant radiotherapy. However, about 30% of patients present with... (Review)
Review
Thymic tumours are rare diseases that for most of the cases are cured with surgery and eventually adjuvant radiotherapy. However, about 30% of patients present with advanced stage or relapsing tumours, which require administration of chemotherapy. While cisplatin-adriamycin-cyclophosphamide combination is regularly prescribed, other drugs have been assessed in the literature. Our aim is to evaluate the effectiveness (response rate) of systemic treatments, whatever the therapeutic line, including chemotherapy, targeted therapies and immunotherapies, in thymoma and thymic carcinoma, using the principles of evidence-based medicine. A systematic review was designed using the PICO system, by an experienced librarian and clinicians' experts in thoracic oncology, through the Ovid Medline system. Only phase II-IV trials and retrospective studies including at least 14 patients treated with the same regimen were considered. Articles were independently selected by at least two investigators. Fifty-five eligible articles were retrieved. Sixty% were dealing with platinum-based regimens, mainly cisplatin, and showed overall similar activity (mostly response rate above 50%) independently of the line of treatment or histological type (thymoma versus thymic carcinoma). Non-platinum based regimens included octreotide-prednisone and capecitabine-gemcitabine. Promising data of immunotherapy with antiPDL1 antibody (pembrolizumab) requires confirmation. Based on available data, the most popular and active regimens are cisplatin-anthracycline (CAP or ADOC) or cisplatin-etoposide combinations that should be recommended when considering first-line chemotherapy in thymoma or thymic carcinoma.
Topics: Anthracyclines; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Female; Humans; Male; Neoplasm Recurrence, Local; Survival Analysis; Thymoma; Thymus Neoplasms
PubMed: 30527189
DOI: 10.1016/j.lungcan.2018.10.018 -
Acta Oncologica (Stockholm, Sweden) Feb 2018advanced-stage non-small cell lung cancer (NSCLC) is characterized by having limited treatment options and thus a poor prognosis. However, new treatment options, in the... (Review)
Review
BACKGROUND
advanced-stage non-small cell lung cancer (NSCLC) is characterized by having limited treatment options and thus a poor prognosis. However, new treatment options, in the form of targeted agents (TA), have emerged during recent years. This systematic review aims to provide an overview of the accessible literature in PubMed evaluating TA used on NSCLC patients, and the resulting survival outcomes.
METHOD
this systematic literature review was conducted by reviewing all relevant literature in PubMed. Six separate searches were performed: Three searches where controlled entry terms were used and three free text searches. Furthermore, other relevant publications were included manually. A total of seventy-two studies met the search criteria and were thus further analyzed and evaluated.
RESULTS
In the included studies, various TAs and their effect on different molecular targets have been evaluated. Clinical responses vary considerably among the different genetic aberrations. The majority of studies evaluated TA for epidermal growth factor receptor (EGFR) mutations and TA for echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK) rearrangements. Studies regarding the use of TA for Rat sarcoma (RAS), rapidly accelerated fibrosarcoma (RAF), ROS proto-oncogene 1 (ROS1) rearrangement, Receptor tyrosine-protein kinase erbB-2 (ERBB2), Phosphatidylinositol 3-kinase (PIK3CA)/v-akt murine thymoma viral oncogene homolog; protein kinase B(AKT)/Phosphatase and tensin homolog deleted on chromosome 10(PTEN), The mammalian target of rapamycin (mTOR), and Mesenchymal-epithelial transition factor (MET) were included as well. In general, studies comparing treatment outcomes in EGFR-mutated patients and EML4-ALK (ALK) rearranged patients after use of either TA or standard chemotherapy, present significant better results after TA.
CONCLUSIONS
This systematic review provides an overview of available literature in PubMed regarding NSCLC and TA. Included studies point toward that TA appears to be a promising therapeutic tool in treating NSCLC patients and use of TA is expected to result in improved treatment outcomes.
Topics: Antineoplastic Agents; Carcinoma, Non-Small-Cell Lung; Humans; Lung Neoplasms; Molecular Targeted Therapy; Proto-Oncogene Mas
PubMed: 29172833
DOI: 10.1080/0284186X.2017.1404634 -
Chinese Medical Journal Jul 2017Good's syndrome (GS) is a rare disease characterized by thymoma, hypogammaglobulinemia, low or absent B-cells, decreased T-cells, an inverted CD4+/CD8+ T-cell ratio and... (Review)
Review
BACKGROUND
Good's syndrome (GS) is a rare disease characterized by thymoma, hypogammaglobulinemia, low or absent B-cells, decreased T-cells, an inverted CD4+/CD8+ T-cell ratio and reduced T-cell mitogen proliferative responses. GS is difficult to diagnose preoperatively due to its rarity and lack of typical symptoms, the characteristics of Chinese GS patients are still lacking. This study aimed to systematically review all the clinical, laboratory, and immunologic findings of reported cases of Chinese patients with GS.
METHODS
We searched for case reports and articles up to January 2017 using PubMed, China National Knowledge Infrastructure, Wangfang database and China Science and Technology Journal Database with the following words in combinations as key words: "thymoma," "hypogammaglobulinemia," and "Good's syndrome." The text words and MeSH terms were entered depending on the databases characteristics. The reference lists from retrieved articles were also screened for additional applicable studies. The authors were restricted to Chinese. There was no language restriction.
RESULTS
Forty-seven patients were reported in 27 studies. We found that GS has a nationwide distribution and that most cases (83%) have been described on the mainland of China. The initial clinical presentation is varied, ranging from symptoms related to the thymoma to infections resulting from immunodeficiency. Type AB (50%) is the most common histologic type of thymomas in Chinese GS patients according to the World Health Organization classification of thymomas. With respect to infection, sinopulmonary infection (74%) is the most common type, followed by skin infection (10%) and intestinal tract infection (10%). Diarrhea was presented in 36% of patients, and autoimmune manifestations were presented in 36% of patients.
CONCLUSIONS
GS is a rare association of thymoma and immunodeficiency with a poor prognosis. Astute clinical acumen and increased awareness of the clinical and immunological profile of GS are needed to increase early diagnosis, that would benefit improved therapeutic effects.
Topics: Agammaglobulinemia; Animals; China; Humans; Immunologic Deficiency Syndromes; Rare Diseases; Thymoma; Thymus Neoplasms
PubMed: 28639577
DOI: 10.4103/0366-6999.208234 -
Medicine Jan 2017Although hyperthermic intraperitoneal chemotherapy (HIPEC) has been widely used to treat malignant ascites or as a preventive strategy for microscopic carcinomatosis... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Although hyperthermic intraperitoneal chemotherapy (HIPEC) has been widely used to treat malignant ascites or as a preventive strategy for microscopic carcinomatosis following surgical resection of abdominal tumors, application of hyperthermic intrathoracic chemotherapy (HITHOC) in the treatment of malignant pleural effusion is limited. The objective of the current study was to conduct a systematic review and meta-analysis on the application of HITHOC in the palliative treatment of malignant pleural effusion.
METHODS
After thorough searching of online databases, total 27 articles were included into qualitative systematic review and 5 of them were used to conduct qualitative meta-analysis.
RESULTS
It was found that most of HITHOC was used in combination of cytoreductive surgery (CRS) including pleurectomy/decortication or after surgical resection of primary tumors, which mainly were lung cancer, thymoma or thymic carcinoma, breast cancer, and ovarian cancer. Patients who received HITHOC had significantly longer median survival length compared to the patients without HITHOC (Hedges g = 0.763, P < 0.001). In addition, HITHOC therapy was favored (Hedges g = 0.848, P < 0.001) in terms of median survival length, tumor-free survival rate, with tumor survival rate or Karnofsky performance status (KPS) scale.
CONCLUSION
HITHOC is a safe and effective therapy in controlling pleural effusion and increasing patient's survival rate.
Topics: Antineoplastic Agents; Chemotherapy, Cancer, Regional Perfusion; Combined Modality Therapy; Cytoreduction Surgical Procedures; Humans; Hyperthermia, Induced; Neoplasm Staging; Palliative Care; Pleural Effusion, Malignant; Survival Analysis; Thoracic Cavity; Thoracic Surgical Procedures
PubMed: 28072694
DOI: 10.1097/MD.0000000000005532 -
International Journal of Radiation... Apr 2016To evaluate the survival impact of postoperative radiation therapy (PORT) in stage II to IV thymomas, using systematic review and meta-analysis. (Meta-Analysis)
Meta-Analysis Review
PURPOSE
To evaluate the survival impact of postoperative radiation therapy (PORT) in stage II to IV thymomas, using systematic review and meta-analysis.
METHODS AND MATERIALS
A database search was conducted with EMBASE, PubMed, Web of Science, Cochrane Library, and Ovid from inception to August 2015. Thymic carcinomas were excluded, and studies comparing overall survival (OS) with and without PORT in thymomas were included. The hazard ratios (HRs) of OS were extracted, and a random-effects model was used in the pooled analysis.
RESULTS
Seven retrospective series with a total of 1724 patients were included and analyzed. Almost all of the patients underwent macroscopically complete resection, and thymoma histology was confirmed by the World Health Organization criteria. In the overall analysis of stage II to IV thymomas, OS was not altered with the receipt of PORT (HR 0.79, 95% confidence interval [CI] 0.58-1.08). Although PORT was not associated with survival difference in Masaoka stage II disease (HR 1.45, 95% CI 0.83-2.55), improved OS was observed with the addition of PORT in the discrete pooled analysis of stage III to IV (HR 0.63, 95% CI 0.40-0.99). Significant heterogeneity and publication bias were not found in the analyses.
CONCLUSIONS
From the present meta-analysis of sole primary thymomas, we suggest the potential OS benefit of PORT in locally advanced tumors with macroscopically complete resection, but not in stage II disease. Further investigations with sufficient survival data are needed to establish detailed treatment indications.
Topics: Humans; Neoplasm Staging; Observational Studies as Topic; Postoperative Care; Prognosis; Publication Bias; Radiotherapy, Adjuvant; Retrospective Studies; Survival Analysis; Thymoma; Thymus Neoplasms
PubMed: 27026316
DOI: 10.1016/j.ijrobp.2016.01.007 -
Journal of Thoracic Oncology : Official... Jan 2016Complete resection is the standard of care for treatment of thymic malignancies. The use of minimally invasive surgery remains controversial. We searched online... (Comparative Study)
Comparative Study Meta-Analysis Review
Complete resection is the standard of care for treatment of thymic malignancies. The use of minimally invasive surgery remains controversial. We searched online databases and identified studies from 1995 to 2014 that compared minimally invasive to open thymectomy for thymic malignancies. Study end points included operative blood loss, operative time, respiratory complications, cardiac complications, length of hospital stay, R0 resection, and recurrence. We summarized outcomes across studies using random-effects meta-analysis to account for study heterogeneity. We calculated ORs for binary outcomes and standardized mean differences for continuous outcomes. We calculated incidence rate ratios for the number of recurrences, accounting for total person-time observed in each study. Of 516 potential reference studies, 30 with a total of 2038 patients met the inclusion criteria. Patients with Masaoka stage I or II thymic malignancy constituted 94.89% of those in the minimally invasive surgery (MIS) group and 78.62% of those in open thymectomy (open) group. Mean tumor size was 4.09 cm (MIS) versus 4.80 (open). Of the 1355 MIS cases, 32 were converted to open cases. Patients in the MIS group had significantly less blood loss; however, no significant differences in operating time, respiratory complications, cardiac complications, or overall complications were identified. Length of stay was shorter for patients in the MIS group. When patients with Masaoka stage I and II thymic malignancy only were analyzed, there was no difference in rate of R0 resection or overall recurrence rate. One postoperative death occurred in the open group. The results of this unadjusted meta-analysis of published reports comparing minimally invasive with open thymectomy suggest that in selected patients with thymic malignancy, minimally invasive thymectomy is safe and can achieve oncologic outcomes similar to those of open thymectomy.
Topics: Humans; Minimally Invasive Surgical Procedures; Risk Assessment; Thymectomy; Thymoma; Thymus Neoplasms
PubMed: 26762737
DOI: 10.1016/j.jtho.2015.08.004 -
Medical Science Monitor : International... Aug 2015The association between PTPN22 R620W polymorphism and risk of myasthenia gravis (MG) remains controversial. Therefore, we did this meta-analysis to investigate this... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The association between PTPN22 R620W polymorphism and risk of myasthenia gravis (MG) remains controversial. Therefore, we did this meta-analysis to investigate this association.
MATERIAL AND METHODS
We did a comprehensive search in PubMed, Medline, Embase, CNKI (China National Knowledge Infrastructure), and Wanfang electronic databases to retrieve relevant articles. The overall effect was measured by odds ratios (ORs) with its 95% confidence intervals (CIs). Statistical analyses were conducted with STATA software.
RESULTS
Overall, a total of 7 case-control studies with 2802 cases and 3730 controls were finally included in this review. PTPN22 R620W polymorphism was significantly associated with an increased risk of MG (OR=1.57; 95% CI, 1.34-1.82; I(2)=31%). In the subgroup analysis, thymoma patients were significantly associated with risk of MG (OR=1.59; 95% CI, 1.28-1.98; I(2)=0%). However, non-thymoma patients with this polymorphism did not have increased MG risk (OR=1.36; 95% CI, 0.86-2.15; I(2)=77%). In addition, PTPN22 R620W polymorphism showed increased early-onset myasthenia gravis (EOMG) risk (OR=2.38; 95% CI, 1.52-3.71; I(2)=0%).
CONCLUSIONS
This meta-analysis shows a significant association between PTPN22 R620W polymorphism and MG risk.
Topics: Genetic Predisposition to Disease; Humans; Myasthenia Gravis; Polymorphism, Genetic; Protein Tyrosine Phosphatase, Non-Receptor Type 22
PubMed: 26318187
DOI: 10.12659/MSM.894307 -
Lung Cancer (Amsterdam, Netherlands) Oct 2014To perform a systematic review and meta-analysis of published data on the role of fluorine-18-fluorodeoxyglucose positron emission tomography ((18)F-FDG PET) in... (Meta-Analysis)
Meta-Analysis Review
AIM
To perform a systematic review and meta-analysis of published data on the role of fluorine-18-fluorodeoxyglucose positron emission tomography ((18)F-FDG PET) in predicting the WHO grade of malignancy in thymic epithelial tumors (TETs).
METHODS
A comprehensive literature search of studies published up to March 2014 was performed. Data on maximum standardized uptake value (SUVmax) in patients with low-risk thymomas (A, AB, B1), high-risk thymomas (B2, B3) and thymic carcinomas (C) according to the WHO classification were collected when reported by the retrieved articles. The comparison of mean SUVmax between low-risk thymomas, high-risk thymomas and thymic carcinomas was expressed as weighted mean difference (WMD) and a pooled WMD was calculated including 95% confidence interval (95%CI).
RESULTS
Eleven studies were selected for the meta-analysis. The pooled WMD of SUVmax between high-risk and low-risk thymomas was 1.2 (95%CI: 0.4-2.0). The pooled WMD of SUVmax between thymic carcinomas and low-risk thymomas was 4.8 (95%CI: 3.4-6.1). Finally, the pooled WMD of SUVmax between thymic carcinomas and high-risk thymomas was 3.5 (95%CI: 2.7-4.3).
CONCLUSIONS
(18)F-FDG PET may predict the WHO grade of malignancy in TETs. In particular, we demonstrated a statistically significant difference of SUVmax between the different TETs (low-grade thymomas, high-grade thymomas and thymic carcinomas).
Topics: Fluorodeoxyglucose F18; Humans; Neoplasm Grading; Neoplasm Staging; Neoplasms, Glandular and Epithelial; Positron-Emission Tomography; Thymoma; Thymus Neoplasms; Tomography, X-Ray Computed
PubMed: 25175317
DOI: 10.1016/j.lungcan.2014.08.008