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Blood Sep 2022Primary mediastinal large B-cell lymphoma (PMBCL) is a separate entity in the World Health Organization's classification, based on clinicopathologic features and a...
Primary mediastinal large B-cell lymphoma (PMBCL) is a separate entity in the World Health Organization's classification, based on clinicopathologic features and a distinct molecular signature that overlaps with nodular sclerosis classic Hodgkin lymphoma (cHL). Molecular classifiers can distinguish PMBCL from diffuse large B-cell lymphoma (DLBCL) using ribonucleic acid derived from paraffin-embedded tissue and are integral to future studies. However, given that ∼5% of DLBCL can have a molecular PMBCL phenotype in the absence of mediastinal involvement, clinical information remains critical for diagnosis. Studies during the past 10 to 20 years have elucidated the biologic hallmarks of PMBCL that are reminiscent of cHL, including the importance of the JAK-STAT and NF-κB signaling pathways, as well as an immune evasion phenotype through multiple converging genetic aberrations. The outcome of PMBCL has improved in the modern rituximab era; however, whether there is a single standard treatment for all patients and when to integrate radiotherapy remains controversial. Regardless of the frontline therapy, refractory disease can occur in up to 10% of patients and correlates with poor outcome. With emerging data supporting the high efficacy of PD1 inhibitors in PMBCL, studies are underway that integrate them into the up-front setting.
Topics: Hodgkin Disease; Humans; Lymphoma, Large B-Cell, Diffuse; Mediastinal Neoplasms; Mediastinum; Rituximab
PubMed: 34496020
DOI: 10.1182/blood.2020008376 -
The Journal of Cardiovascular Surgery Dec 2022Superior vena cava (SVC) syndrome refers to the clinical manifestations of cerebral venous hypertension secondary to obstruction of the SVC and/or the innominate veins....
Superior vena cava (SVC) syndrome refers to the clinical manifestations of cerebral venous hypertension secondary to obstruction of the SVC and/or the innominate veins. The most common cause of SVC syndrome is malignancy like small cell lung cancer and non-Hodgkin lymphoma, but there is an increasing trend of benign etiologies secondary to thrombosis due to central lines/ pacemakers or mediastinal fibrosis. Supportive measures include head elevation, diuresis, supplemental oxygen, and steroids. Thrombolysis with or without endovenous stenting is required emergently in those with airway compromise or symptoms secondary to cerebral edema. Definitive treatment in those with malignancy is multidisciplinary; this requires radiotherapy, chemotherapy, SVC stenting, oncologic surgery and SVC bypass or reconstruction. Endovascular treatment is the primary modality for palliation in malignancy and in those with benign etiology. Surgery is reserved for those who have failed or are unsuitable for endovascular treatment. In patients with benign disease endovenous stenting and open surgery provide excellent symptom relief and are safe and effective.
Topics: Humans; Superior Vena Cava Syndrome; Vena Cava, Superior; Stents; Mediastinitis; Thrombosis
PubMed: 36469045
DOI: 10.23736/S0021-9509.22.12448-1 -
Clinical Microbiology and Infection :... Jan 2020Mediastinitis is a rare but severe infection, defined as an inflammation of the connective tissues and structures within the mediastinum. Due to its proximity to vital... (Review)
Review
BACKGROUND
Mediastinitis is a rare but severe infection, defined as an inflammation of the connective tissues and structures within the mediastinum. Due to its proximity to vital structures, mediastinitis represents a highly morbid pathological process associated with a high risk of mortality. In most cases mediastinitis requires treatment in the intensive care unit.
OBJECTIVES
To highlight to the reader the clinical features of mediastinitis, to attempt to define each clinical scenario, to describe the responsible pathogens and finally to depict both the medical and surgical treatments.
SOURCES
We performed a literature search of the PubMed and Cochrane libraries, limited for articles published between January 2003 and December 2018, reporting on acute mediastinitis.
CONTENT
The term covers different entities of different aetiologies including deep sternal wound infection related to sternotomy; oesophageal perforation or anastomosis leakage; and finally descending necrotizing mediastinitis, often secondary to oropharyngeal abscess. The responsible pathogens and therefore subsequent management depends on the underlying aetiology. Empirical antimicrobial therapy should cover the suspected microorganisms while surgery and supportive measures should aim to reduce the inoculum of pathogens by providing adequate drainage and debridement.
IMPLICATIONS
Literature concerning mediastinitis in the intensive care unit is relatively scarce. We have collated the evidence and reviewed the different causes and treatment options of acute mediastinitis with a particular focus on microbiological epidemiology. Future research in larger cohorts is needed to better understand the treatment of this difficult disease.
Topics: Abscess; Anti-Bacterial Agents; Bacteria; Bacterial Infections; Debridement; Drainage; Humans; Intensive Care Units; Mediastinitis; Oropharynx; Sepsis
PubMed: 31306791
DOI: 10.1016/j.cmi.2019.07.005 -
British Journal of Haematology Jun 2020Aggressive B-cell non-Hodgkin lymphoma (B-NHL) accounts for ≈60% of NHL in children/adolescents. In newly diagnosed Burkitt lymphoma and diffuse large B-cell lymphoma,... (Review)
Review
Aggressive B-cell non-Hodgkin lymphoma (B-NHL) accounts for ≈60% of NHL in children/adolescents. In newly diagnosed Burkitt lymphoma and diffuse large B-cell lymphoma, short intensive multiagent chemotherapy is associated with a five-year event-free survival of around 90%. Very few children/adolescents with aggressive B-NHL show a relapsed/refractory (r/r) disease. The outcome is poor, with cure rates <30%, and there is no standard of care. Rituximab-containing salvage regimens may provide a complete/partial response in 60-70% of cases. However, long-term survival is <10% for non-transplanted patients. Autologous or allogeneic haematopoietic stem cell transplant is, nowadays, the best option for responding patients, with survival rates around 50%. The benefit of autologous versus allogeneic HSCT is not clear. Numerous novel therapies for r/r B-NHL are currently being tested in adults, including next-generation monoclonal antibodies, novel cellular therapy strategies and therapies directed against new targets. Some are under investigation also in children/adolescents, with promising preliminary results.
Topics: Adolescent; Antineoplastic Combined Chemotherapy Protocols; Central Nervous System Neoplasms; Child; Combined Modality Therapy; Cranial Irradiation; Female; Hematopoietic Stem Cell Transplantation; Humans; Immunotherapy; Kaplan-Meier Estimate; Lymphoma, B-Cell; Male; Mediastinal Neoplasms; Prognosis; Recurrence; Risk Factors; Salvage Therapy; Therapies, Investigational; Treatment Outcome; Young Adult
PubMed: 32141616
DOI: 10.1111/bjh.16461 -
Journal of Clinical Oncology : Official... Dec 2019Patients with relapsed or refractory primary mediastinal large B-cell lymphoma (rrPMBCL) have a poor prognosis, and their treatment represents an urgent and unmet need....
PURPOSE
Patients with relapsed or refractory primary mediastinal large B-cell lymphoma (rrPMBCL) have a poor prognosis, and their treatment represents an urgent and unmet need. Because PMBCL is associated with genetic aberrations at 9p24 and overexpression of programmed cell death-1 (PD-1) ligands (PD-L1), it is hypothesized to be susceptible to PD-1 blockade.
METHODS
In the phase IB KEYNOTE-013 (ClinicalTrials.gov identifier: NCT01953692) and phase II KEYNOTE-170 (ClinicalTrials.gov identifier: NCT02576990) studies, adults with rrPMBCL received pembrolizumab for up to 2 years or until disease progression or unacceptable toxicity. The primary end points were safety and objective response rate in KEYNOTE-013 and objective response rate in KEYNOTE-170. Secondary end points included duration of response, progression-free survival, overall survival, and safety. Exploratory end points included association between biomarkers and pembrolizumab activity.
RESULTS
The objective response rate was 48% (7 complete responses; 33%) among 21 patients in KEYNOTE-013 and 45% (7 complete responses; 13%) among 53 patients in KEYNOTE-170. After a median follow-up time of 29.1 months in KEYNOTE-013 and 12.5 months in KEYNOTE-170, the median duration of response was not reached in either study. No patient with complete response experienced progression, including 2 patients with complete response for at least 1 year off therapy. Treatment-related adverse events occurred in 24% of patients in KEYNOTE-013 and 23% of patients in KEYNOTE-170. There were no treatment-related deaths. Among 42 evaluable patients, the magnitude of the 9p24 gene abnormality was associated with PD-L1 expression, which was itself significantly associated with progression-free survival.
CONCLUSION
Pembrolizumab is associated with high response rate, durable activity, and a manageable safety profile in patients with rrPMBCL.
Topics: Adult; Antibodies, Monoclonal, Humanized; Antineoplastic Agents, Immunological; Disease Progression; Drug Resistance, Neoplasm; Europe; Female; Humans; Lymphoma, B-Cell; Male; Mediastinal Neoplasms; Middle Aged; Neoplasm Recurrence, Local; Progression-Free Survival; Risk Assessment; Risk Factors; South America; Time Factors; United States; Young Adult
PubMed: 31609651
DOI: 10.1200/JCO.19.01389 -
Jornal Brasileiro de Pneumologia :... Jul 2019
Topics: Adult; Barotrauma; Cocaine-Related Disorders; Humans; Male; Mediastinal Emphysema; Radiography, Thoracic; Tomography, X-Ray Computed
PubMed: 31365685
DOI: 10.1590/1806-3713/e20190169 -
The British Journal of Radiology Dec 2019Erdheim-Chester disease (ECD) is a rare non-Langerhans cell histiocytosis which can have a broad range of clinical and radiological presentations. Typically, ECD affects... (Review)
Review
Erdheim-Chester disease (ECD) is a rare non-Langerhans cell histiocytosis which can have a broad range of clinical and radiological presentations. Typically, ECD affects multiple organ systems, with skeletal involvement present in almost all ECD patients and cardiothoracic manifestations in more than half. Cardiac and thoracic involvement contributes significantly to morbidity and mortality in affected patients and may have prognostic implications. The diagnosis of ECD can be challenging due to its rarity and similarity to other systemic disease processes. Although the diagnosis can be suggested on imaging, histopathology and immunohistochemistry are required for confirmation. We describe the multimodal imaging features of mediastinal, cardiac, pleural and lung parenchymal ECD. This review identifies the most common radiological manifestations of cardiac and thoracic ECD on contrast-enhanced CT, fluorine-fludeoxyglucose positron emission tomography/CT and cardiac MRI, and highlights the role of these cross-sectional techniques in disease diagnosis.
Topics: Contrast Media; Erdheim-Chester Disease; Fluorodeoxyglucose F18; Heart Diseases; Humans; Lung Diseases; Magnetic Resonance Imaging; Mediastinal Diseases; Multimodal Imaging; Pleural Diseases; Positron Emission Tomography Computed Tomography; Radiopharmaceuticals; Tomography, X-Ray Computed
PubMed: 31386554
DOI: 10.1259/bjr.20190473 -
Blood Jul 2023Previous analyses of the phase 2 KEYNOTE-170 (NCT02576990) study demonstrated effective antitumor activity and acceptable safety of pembrolizumab 200 mg given every 3... (Clinical Trial)
Clinical Trial
Previous analyses of the phase 2 KEYNOTE-170 (NCT02576990) study demonstrated effective antitumor activity and acceptable safety of pembrolizumab 200 mg given every 3 weeks for up to 35 cycles (∼2 years) in patients with relapsed/refractory (R/R) primary mediastinal B-cell lymphoma (PMBCL) whose disease progressed after or who were ineligible for autologous stem cell transplantation. The end points included objective response rate (ORR), progression-free survival (PFS), and duration of response (DOR) according to the investigator per 2007 Response Criteria; overall survival (OS); and safety. In this final analysis, median duration of follow-up was 48.7 months (range, 41.2-56.2). The ORR was 41.5% (complete response, 20.8%; partial response, 20.8%). The median DOR was not reached; no patients who achieved a complete response progressed at the data cutoff. The median PFS was 4.3 months; the 4-year PFS rate was 33.0%. The median OS was 22.3 months; the 4-year OS rate was 45.3%. At the data cutoff, 30 patients (56.6%) had any-grade treatment-related adverse events (AEs); the most common were neutropenia, asthenia, and hypothyroidism. Grade 3/4 treatment-related AEs occurred in 22.6% of the patients; no grade 5 AEs occurred. After 4 years of follow-up, pembrolizumab continued to provide durable responses, with promising trends for long-term survival and acceptable safety in R/R PMBCL.
Topics: Adult; Humans; Antibodies, Monoclonal, Humanized; Hematopoietic Stem Cell Transplantation; Lymphoma, Large B-Cell, Diffuse; Mediastinal Neoplasms; Thymus Neoplasms; Transplantation, Autologous
PubMed: 37130017
DOI: 10.1182/blood.2022019340 -
Internal Medicine (Tokyo, Japan) Jan 2022
Topics: Esophageal Diseases; Esophageal Perforation; Humans; Mediastinal Diseases; Rupture, Spontaneous
PubMed: 34219113
DOI: 10.2169/internalmedicine.7807-21 -
CMAJ : Canadian Medical Association... Sep 2021
Topics: Alcohol Drinking; Esophageal Perforation; Humans; Hydropneumothorax; Male; Mediastinal Diseases; Mediastinal Emphysema; Middle Aged; Vomiting
PubMed: 34580144
DOI: 10.1503/cmaj.202893