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Evidence-based Mental Health Nov 2019The awareness and understanding of autoimmune encephalitis are blossoming in neurology, and patients are being diagnosed and successfully treated with immunotherapy. The... (Review)
Review
The awareness and understanding of autoimmune encephalitis are blossoming in neurology, and patients are being diagnosed and successfully treated with immunotherapy. The diverse symptomatology associated with autoimmune encephalitis means that patients may present initially to mental health services, which are, as yet, less well equipped to identify and investigate such phenomena. Older adult mental health services are used to managing complexity, but the range of pathologies presenting with unusual symptoms that may mimic autoimmune encephalitis is wide and there is no clear guidance as to when and how to investigate for possible autoimmune encephalitis. This paper examines the evidence supporting investigation and management strategies for patients with possible autoimmune encephalitis presenting to older adult psychiatrists.
Topics: Aging; Autoimmune Diseases of the Nervous System; Humans; Limbic Encephalitis; Paraneoplastic Syndromes, Nervous System
PubMed: 31537612
DOI: 10.1136/ebmental-2019-300110 -
Endocrine May 2019Our aim was to assess the prevalence of endocrine paraneoplastic syndromes (EPNS) in neuroendocrine neoplasms (NENs) and estimate its impact on patient outcomes.
OBJECTIVE
Our aim was to assess the prevalence of endocrine paraneoplastic syndromes (EPNS) in neuroendocrine neoplasms (NENs) and estimate its impact on patient outcomes.
DESIGN
This is a retrospective analysis of 834 patients with NENs (611 gastrointestinal, 166 thoracic, 57 of unknown and various other primary origin). We included 719 consecutive NEN patients treated at EKPA-Laiko Hospital, Athens, Greece and 115 patients with lung carcinoid (LC) treated at Uppsala University Hospital, Uppsala, Sweden. EPNS diagnosis was based on standard criteria.
METHODS
Twenty-one patients with EPNS were detected: 16 with ectopic Cushing's syndrome (ECS), one with hypercalcaemia due to parathyroid hormone-related protein (PTHrP) secretion, three with hypercalcitonaemia and one patient with dual secretion of calcitonin and beta-human chorionic gonadotropin (β-HCG). All tumours were well-differentiated; 10 patients had Stage IV disease at diagnosis.
RESULTS
The prevalence of EPNS in the Greek cohort was 1.9%, whereas that of ECS among LC patients in both centres was 6.7%. Median overall survival (OS) for patients with EPNS was 160.7 months (95%CI, 86-235.4) and median event-free survival (EFS) was 25.9 months (95%CI, 0-57.2). Patients presenting with EPNS prior to NEN diagnosis had longer EFS compared to patients with synchronous or metachronous EPNS (log-rank P = 0.013). Patients with ECS of extra-thoracic origin demonstrated shorter OS and EFS compared to patients with ECS of lung or thymic origin (log-rank P = 0.001 and P < 0.001, respectively). LC patients with and without ECS were comparable in 5-year and 10-year OS rates (66.7% and 33.3% versus 89.8% and 60.2%, respectively; 95%CI [189.6-300.4 months], log-rank P = 0.94) and in median EFS, 67 versus 183 months, 95%CI [50.5-207.5], log-rank P = 0.12).
CONCLUSION
EPNS are relatively rare in patients with NENs and mainly concern well-differentiated tumours of the foregut. Among patients with EPNS, LC-related ECS may not adversely affect patient outcomes when diagnosed prior to NEN and effectively been treated.
Topics: Adult; Aged; Female; Gastrointestinal Neoplasms; Greece; Humans; Male; Middle Aged; Neuroendocrine Tumors; Paraneoplastic Syndromes; Prevalence; Retrospective Studies; Sweden; Thoracic Neoplasms
PubMed: 30280284
DOI: 10.1007/s12020-018-1773-3 -
Journal of Thoracic Oncology : Official... Mar 2018Thymic epithelial tumors (TETs) are associated with paraneoplastic/autoimmune (PN/AI) syndromes. Myasthenia gravis is the most common PN/AI syndrome associated with TETs.
INTRODUCTION
Thymic epithelial tumors (TETs) are associated with paraneoplastic/autoimmune (PN/AI) syndromes. Myasthenia gravis is the most common PN/AI syndrome associated with TETs.
METHODS
The International Thymic Malignancy Interest Group retrospective database was examined to determine (1) baseline and treatment characteristics associated with PN/AI syndromes and (2) the prognostic role of PN/AI syndromes for patients with TETs. The competing risks model was used to estimate cumulative incidence of recurrence (CIR) and the Kaplan-Meier method was used to calculate overall survival (OS). A Cox proportional hazards model was used for multivariate analysis.
RESULTS
A total of 6670 patients with known PN/AI syndrome status from 1951 to 2012 were identified. PN/AI syndromes were associated with younger age, female sex, thymoma histologic type, earlier stage, and an increased rate of total thymectomy and complete resection status. There was a statistically significant lower CIR in the group with a PN/AI syndrome than in the group without a PN/AI syndrome (10-year CIR 17.3% versus 21.2%, respectively [p = 0.0003]). The OS was improved in the group with a PN/AI syndrome compared to the group without a PN/AI syndrome (median OS 21.6 years versus 17.0 years, respectively [hazard ratio = 0.63, 95% confidence interval: 0.54-0.74, p < 0.0001]). However, in the multivariate model for recurrence-free survival and OS, PN/AI syndrome was not an independent prognostic factor.
DISCUSSION
Previously, there have been mixed data regarding the prognostic role of PN/AI syndromes for patients with TETs. Here, using the largest data set in the world for TETs, PN/AI syndromes were associated with favorable features (i.e., earlier stage and complete resection status) but were not an independent prognostic factor for patients with TETs.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Child; Child, Preschool; Databases, Factual; Female; Humans; Male; Middle Aged; Paraneoplastic Syndromes; Retrospective Studies; Thymus Neoplasms; Young Adult
PubMed: 29191778
DOI: 10.1016/j.jtho.2017.11.118 -
Current Opinion in Rheumatology Nov 2015Recent data suggest a paraneoplastic mechanism of scleroderma pathogenesis in unique subsets of scleroderma patients. In this article, we review these data, explore... (Review)
Review
PURPOSE OF REVIEW
Recent data suggest a paraneoplastic mechanism of scleroderma pathogenesis in unique subsets of scleroderma patients. In this article, we review these data, explore potential links between cancer and scleroderma, and propose an approach to malignancy screening in scleroderma.
RECENT FINDINGS
Emerging data have demonstrated that patients with scleroderma and RNA polymerase III autoantibodies have a significantly increased risk of cancer within a few years of scleroderma onset. Genetic alterations in the gene encoding RNA polymerase III (POLR3A) have been identified, and patients with somatic mutations in POLR3A have evidence of mutation specific T-cell immune responses with generation of cross-reactive RNA polymerase III autoantibodies. These data strongly suggest that scleroderma is a by-product of antitumor immune responses in some patients. Additional epidemiologic data demonstrate that patients developing scleroderma at older ages may also have a short cancer-scleroderma interval, suggestive of paraneoplastic disease.
SUMMARY
Scleroderma may be a paraneoplastic disease in unique patient subsets. Aggressive malignancy screening in these patients may aid in early cancer detection. Further study is required to determine whether cancer therapy could improve scleroderma outcomes in this patient population.
Topics: Early Detection of Cancer; Humans; Neoplasms; Paraneoplastic Syndromes; Scleroderma, Systemic
PubMed: 26352736
DOI: 10.1097/BOR.0000000000000222 -
Nature Communications Feb 2024Paraneoplastic syndromes occur in cancer patients and originate from dysfunction of organs at a distance from the tumor or its metastasis. A wide range of organs can be...
Paraneoplastic syndromes occur in cancer patients and originate from dysfunction of organs at a distance from the tumor or its metastasis. A wide range of organs can be affected in paraneoplastic syndromes; however, the pathological mechanisms by which tumors influence host organs are poorly understood. Recent studies in the fly uncovered that tumor secreted factors target host organs, leading to pathological effects. In this study, using a Drosophila gut tumor model, we characterize a mechanism of tumor-induced kidney dysfunction. Specifically, we find that Pvf1, a PDGF/VEGF signaling ligand, secreted by gut tumors activates the PvR/JNK/Jra signaling pathway in the principal cells of the kidney, leading to mis-expression of renal genes and paraneoplastic renal syndrome-like phenotypes. Our study describes an important mechanism by which gut tumors perturb the function of the kidney, which might be of clinical relevance for the treatment of paraneoplastic syndromes.
Topics: Animals; Humans; Drosophila; Nephrotic Syndrome; Paraneoplastic Syndromes; Kidney; Signal Transduction; Egg Proteins; Drosophila Proteins
PubMed: 38336808
DOI: 10.1038/s41467-024-45493-8 -
Journal of Investigative Medicine High... 2024Cutaneous paraneoplastic syndromes due to Hodgkin lymphoma present with a wide spectrum of clinical manifestations from generalized pruritus to exfoliative erythroderma....
Cutaneous paraneoplastic syndromes due to Hodgkin lymphoma present with a wide spectrum of clinical manifestations from generalized pruritus to exfoliative erythroderma. We summarize the clinical findings and outcomes of 14 patients with Hodgkin lymphoma and associated cutaneous paraneoplastic syndromes treated at Mayo Clinic over the past 3 decades. Cutaneous paraneoplastic syndromes may be present at the time of lymphoma diagnosis, whereas in other patients, it may appear at the time of relapse, including patients with initial absence of cutaneous manifestations during the initial lymphoma presentation. Our results indicate that complete resolution of the paraneoplastic syndrome is associated with significantly improved overall survival. Recognition of cutaneous paraneoplastic syndromes is a crucial surrogate of relapsed malignancy and treatment requires targeting the underlying malignancy.
Topics: Humans; Hodgkin Disease; Paraneoplastic Syndromes; Male; Female; Middle Aged; Adult; Aged; Young Adult; Skin Diseases; Adolescent
PubMed: 38767173
DOI: 10.1177/23247096241255840 -
Paraneoplastic autoimmunity and small-cell lung cancer: Neurological and serological accompaniments.Thoracic Cancer Apr 2019Paraneoplastic neurological autoimmunity is often associated with small-cell lung cancer (SCLC), a highly malignant neuroendocrine tumor. Paraneoplastic autoimmunity...
Paraneoplastic neurological autoimmunity is often associated with small-cell lung cancer (SCLC), a highly malignant neuroendocrine tumor. Paraneoplastic autoimmunity often correlates with longer survival. We describe the paraneoplastic neurological manifestations of patients with SCLC with and without SCLC-predictive autoantibodies and the correlation between autoimmunity and survival. We reviewed the records of 116 patients (51% male) from the Mayo Clinic with histopathologically confirmed SCLC for whom stored serum was available for neural autoantibody testing. Cancer was limited stage in 41%; the median age at diagnosis was 64 years. Paraneoplastic neurological manifestations were recorded in 61% (decreasing frequency: peripheral neuropathy, dysautonomia, cognitive decline, cerebellar ataxia, neuromuscular junction disorder, seizures, cranial neuropathy, movement disorder, brainstem disorder, or myelopathy). Neural autoantibodies, some with pathogenic potential, were detected in the sera of SCLC patients with and without neurological autoimmunity. The most frequent among patients with neurological manifestations were: anti-neuronal nuclear antibody-type 1, voltage-gated calcium channel (VGCC)-N-type, VGCC-P/Q-type, glutamic acid decarboxylase 65 (GAD65), SOX1, and muscle acetylcholine receptor (AChR); while the most common in patients without neurological manifestations were: GAD65, muscle-AChR, and VGCC-P/Q-type. Neither cancer stage at diagnosis nor survival correlated with neurological manifestations or autoantibody-positivity, except for shorter survival in patients with myelopathy. The only predictor of longer survival was limited-stage disease at diagnosis.
Topics: Adult; Aged; Aged, 80 and over; Autoantibodies; Female; Humans; Lung Neoplasms; Male; Middle Aged; Neoplasm Staging; Paraneoplastic Syndromes, Nervous System; Small Cell Lung Carcinoma; Survival Analysis
PubMed: 30810271
DOI: 10.1111/1759-7714.13009 -
Journal For Immunotherapy of Cancer Dec 2019Paraneoplastic syndromes (PNS) are autoimmune disorders specifically associated with cancer. There are few data on anti-PD-1 or anti-PD-L1 immunotherapy in patients with...
BACKGROUND
Paraneoplastic syndromes (PNS) are autoimmune disorders specifically associated with cancer. There are few data on anti-PD-1 or anti-PD-L1 immunotherapy in patients with a PNS. Our objective was to describe the outcome for patients with a pre-existing or newly diagnosed PNS following the initiation of anti-PD-1 or anti-PD-L1 immunotherapy.
METHODS
We included all adult patients (aged ≥18) treated with anti-PD-1 or anti-PD-L1 immunotherapy for a solid tumor, diagnosed with a PNS, and registered in French pharmacovigilance databases. Patients were allocated to cohorts 1 and 2 if the PNS had been diagnosed before vs. after the initiation of immunotherapy, respectively.
FINDINGS
Of the 1304 adult patients screened between June 27th, 2014, and January 2nd, 2019, 32 (2.45%) had a PNS and were allocated to either cohort 1 (n = 16) or cohort 2 (n = 16). The median (range) age was 64 (45-88). The tumor types were non-small-cell lung cancer (n = 15, 47%), melanoma (n = 6, 19%), renal carcinoma (n = 3, 9%), and other malignancies (n = 8, 25%). Eleven (34%) patients presented with a neurologic PNS, nine (28%) had a rheumatologic PNS, eight (25%) had a connective tissue PNS, and four (13%) had other types of PNS. The highest severity grade for the PNS was 1-2 in 10 patients (31%) and ≥ 3 in 22 patients (69%). Four patients (13%) died as a result of the progression of a neurologic PNS (encephalitis in three cases, and Lambert-Eaton syndrome in one case). Following the initiation of immunotherapy, the PNS symptoms worsened in eight (50%) of the 16 patients in cohort 1.
INTERPRETATION
Our results show that PNSs tend to be worsened or revealed by anti-PD-1 or anti-PD-L1 immunotherapy. Cases of paraneoplastic encephalitis are of notable concern, in view of their severity. When initiating immunotherapy, physicians should carefully monitor patients with a pre-existing PNS.
Topics: Aged; Aged, 80 and over; Antineoplastic Agents, Immunological; Autoimmune Diseases; B7-H1 Antigen; Female; France; Humans; Male; Middle Aged; Neoplasms; Paraneoplastic Syndromes; Programmed Cell Death 1 Receptor; Severity of Illness Index; Symptom Assessment
PubMed: 31796119
DOI: 10.1186/s40425-019-0821-8 -
Journal of Nuclear Medicine : Official... Jul 2017The purpose of this study was to assess the diagnostic performance of whole-body F-FDG PET or F-FDG PET/CT for detection of underlying malignancy in patients with... (Comparative Study)
Comparative Study Meta-Analysis Review
The purpose of this study was to assess the diagnostic performance of whole-body F-FDG PET or F-FDG PET/CT for detection of underlying malignancy in patients with clinically suspected neurologic and nonneurologic paraneoplastic syndromes. A systematic search was performed in PubMed (Medline), Embase, and Scopus (last updated November 2016) to identify relevant published studies reporting the performance of F-FDG PET or F-FDG PET/CT in patients with suspected paraneoplastic syndrome. Histopathologic confirmation or clinical follow-up was considered as the reference standard. Pooled estimates, with 95% confidence intervals (CIs), of sensitivity, specificity, and diagnostic odds ratio were calculated. A summary receiver-operating-characteristic curve was constructed, and the area under the curve (AUC) was determined along with the Q* index. Twenty-one studies including a total of 1,293 individual patients suspected of having a paraneoplastic syndrome and who underwent F-FDG PET or F-FDG PET/CT examinations met our inclusion criteria. There was moderate to high heterogeneity among the included studies. The pooled sensitivity, specificity, and diagnostic odds ratio of F-FDG PET or F-FDG PET/CT for the detection of underlying malignancy were 0.81 (95% CI, 0.76-0.86), 0.88 (95% CI, 0.86-0.90), and 34.03 (95% CI, 18.76-61.72), respectively. The AUC and the Q* index were 0.916 (SE, 0.018) and 0.849, indicating excellent diagnostic accuracy. The diagnostic accuracy was slightly improved after studies with high applicability concerns were excluded (AUC, 0.931; SE, 0.020). In a subgroup analysis, F-FDG PET/CT was found to have a significantly higher specificity (0.89 vs. 0.79) than F-FDG PET alone, with no evidence of significant difference in the overall performance (AUC, 0.930 vs. 0.891; 2-tailed value for difference, 0.31). This meta-analysis of available studies demonstrates that whole-body F-FDG PET or F-FDG PET/CT has high diagnostic accuracy and moderate to high sensitivity and specificity for detection of underlying malignancy in patients suspected of having a paraneoplastic syndrome.
Topics: Fluorodeoxyglucose F18; Incidence; Paraneoplastic Syndromes; Positron Emission Tomography Computed Tomography; Positron-Emission Tomography; Prevalence; Prognosis; Radiopharmaceuticals; Reproducibility of Results; Risk Factors; Sensitivity and Specificity; Whole Body Imaging
PubMed: 27980049
DOI: 10.2967/jnumed.116.183905 -
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