-
Translational Pediatrics May 2021This article reviews the contemporary diagnosis and management of the most common abdominal neoplasms and cystic lesions diagnosed in the fetus. Fetal tumors discussed... (Review)
Review
This article reviews the contemporary diagnosis and management of the most common abdominal neoplasms and cystic lesions diagnosed in the fetus. Fetal tumors discussed include teratomas (sacrococcygeal, cervical or mediastinal), mesoblastic nephroma, nephroblastoma (Wilms' tumor), neuroblastoma, and hepatoblastoma. Fetal abdominal cystic lesions discussed include ovarian cyst, choledochal cyst, intestinal duplication cyst, mesenteric cyst, simple hepatic cyst, and meconium pseudocyst. We discuss the rare indications for fetal intervention or fetal surgery and other perinatal management, including prenatal interventions and fetal surgery for sacrococcygeal teratoma. The lesions reviewed are detected by widespread use of screening ultrasonography during pregnancy. Work-up for these abnormalities may include fetal MRI which enhances the diagnostic accuracy of abdominal tumors and cystic lesions and can aid in characterization of the lesion in relationship to surrounding anatomic structures. Accurate prenatal diagnosis of such lesions permits recommendations for optimal location and timing of delivery, and inclusion of appropriate caregivers and expertise to facilitate postnatal management. Perinatal management of the fetus with a neoplasm requires consideration of the optimal timing and mode of delivery, and pediatric oncology and surgical specialty care. The majority of tumors diagnosed antenatally have good prognosis with current multimodality treatment.
PubMed: 34189111
DOI: 10.21037/tp-20-440 -
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 -
Interactive Cardiovascular and Thoracic... Jun 2022Isolated Chylopericardium (without chylothorax) is a rare clinical disorder that may happen idiopathically or secondary to trauma, radiotherapy, lymphatic anomalies,...
Isolated Chylopericardium (without chylothorax) is a rare clinical disorder that may happen idiopathically or secondary to trauma, radiotherapy, lymphatic anomalies, infections or mediastinal neoplasm. We present a case of middle-aged male with no past medical history of note prior to developing heavy sweating, loss of weight and cough. A series of investigations were done including chest computed tomography which showed enlarged mediastinal lymph nodes leading to uncomplicated mediastinoscopy and lymph node biopsy. Six days after being discharged, he developed dyspnoea and chest pain. Echocardiography revealed massive pericardial effusion. Pericardiocentesis was done and surprisingly revealed milky white chylous fluid. The patient was then successfully managed without the need for further intervention.
Topics: Chylothorax; Humans; Lymph Nodes; Male; Mediastinum; Middle Aged; Pericardial Effusion; Pericardiocentesis
PubMed: 34964452
DOI: 10.1093/icvts/ivab365 -
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 -
BMJ Case Reports Jul 2019A 22-year-old female patient was admitted to hospital after being referred from the oral medicine clinic where she had been seen for persistent gingivitis and mouth...
A 22-year-old female patient was admitted to hospital after being referred from the oral medicine clinic where she had been seen for persistent gingivitis and mouth ulcers. She described an insidious history of persistent fevers, dry cough and unexplained weight loss over 4-6 weeks. Imaging showed extensive bilateral pulmonary nodules with mediastinal lymphadenopathy and two lesions in the pancreas. MRI revealed these lesions to be well-defined fluid-filled cysts in the tail of the pancreas, without features of malignancy. Core biopsies taken from her lung nodules demonstrated features of vasculitis with granulomata. This was consistent with her positive immunology for c-antinuclear cytoplasmic antibodies and proteinase-3, which were sent after her fever failed to settle with antibiotic treatment. In keeping with a diagnosis of vasculitis, the patient showed a significant clinical and biochemical response to intravenous methylprednisolone and high-dose daily prednisolone thereafter.
Topics: Administration, Intravenous; Antibodies, Antineutrophil Cytoplasmic; Diagnosis, Differential; Female; Glucocorticoids; Granulomatosis with Polyangiitis; Humans; Lung; Lymphadenopathy; Mediastinal Neoplasms; Methylprednisolone; Myeloblastin; Pancreas; Treatment Outcome; Young Adult
PubMed: 31289155
DOI: 10.1136/bcr-2018-228693 -
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 -
Journal of Thoracic Oncology : Official... Jul 2023We aimed to prospectively evaluate our previously proposed selective mediastinal lymph node (LN) dissection strategy for peripheral clinical T1N0 invasive NSCLC.
INTRODUCTION
We aimed to prospectively evaluate our previously proposed selective mediastinal lymph node (LN) dissection strategy for peripheral clinical T1N0 invasive NSCLC.
METHODS
This is a multicenter, prospective clinical trial in China. We set six criteria for predicting negative LN stations and finally guiding selective LN dissection. Consolidation tumor ratio less than or equal to 0.5, segment location, lepidic-predominant adenocarcinoma (LPA), negative hilar nodes (stations 10-12), and negative visceral pleural invasion (VPI) were used separately or in combination as predictors of negative LN status in the whole, superior, or inferior mediastinal zone. LPA, hilar node involvement, and VPI were diagnosed intraoperatively. All patients actually underwent systematic mediastinal LN dissection. The primary end point was the accuracy of the strategy in predicting LN involvement. If LN metastasis occurred in certain mediastinal zone that was predicted to be negative, it was considered as an "inaccurate" case.
RESULTS
A total of 720 patients were enrolled. The median number of LN dissected was 15 (interquartile range: 11-20). All negative node status in certain mediastinal zone was correctly predicted by the strategy. Compared with final pathologic findings, the accuracy of frozen section to diagnose LPA, VPI, and hilar node metastasis was 94.0%, 98.9%, and 99.6%, respectively. Inaccurate intraoperative diagnosis of LPA, VPI, or hilar node metastasis did not lead to inaccurate prediction of node-negative status.
CONCLUSIONS
This is the first prospective trial validating the specific mediastinal LN metastasis pattern in cT1N0 invasive NSCLC, which provides important evidence for clinical applications of selective LN dissection strategy.
Topics: Humans; Lung Neoplasms; Prospective Studies; Neoplasm Staging; Carcinoma, Non-Small-Cell Lung; Lymph Node Excision; Lymph Nodes; Adenocarcinoma of Lung; Lymphatic Metastasis; Retrospective Studies
PubMed: 36841542
DOI: 10.1016/j.jtho.2023.02.010 -
Journal of Clinical Oncology : Official... Nov 2019Primary mediastinal B-cell lymphoma (PMBL) is a rare but aggressive non-Hodgkin lymphoma with poor outcomes in patients with relapsed/refractory (R/R) disease. PMBL is...
PURPOSE
Primary mediastinal B-cell lymphoma (PMBL) is a rare but aggressive non-Hodgkin lymphoma with poor outcomes in patients with relapsed/refractory (R/R) disease. PMBL is characterized by high expression of programmed death-1 ligand and variable expression of CD30. Nivolumab, an anti-programmed death-1 immune checkpoint inhibitor, and brentuximab vedotin (BV), an anti-CD30 antibody-drug conjugate, may have synergistic activity in R/R PMBL.
METHODS
The expansion cohort of the open-label, phase I/II CheckMate 436 study enrolled patients with confirmed R/R PMBL who were previously treated with either autologous hematopoietic cell transplantation or two or more prior chemotherapy regimens if ineligible for autologous hematopoietic cell transplantation. Patients received nivolumab (240 mg intravenously) and BV (1.8 mg/kg intravenously) every 3 weeks until disease progression or unacceptable toxicity. Primary end points were investigator-assessed objective response rate (ORR) per the Lugano 2014 criteria and safety.
RESULTS
Thirty patients with PMBL were treated and evaluable. At a median follow-up of 11.1 months, ORR (95% CI) was 73% (54% to 88%), with a 37% complete remission rate per investigator, and ORR of 70% (51% to 85%), with a 43% complete metabolic response rate per independent review. Median duration of response, median progression-free survival, and median overall survival have not been reached. Eleven responders had consolidation with autologous (n = 5) or allogeneic (n = 6) transplantation. Treatment-related adverse events were reported in 25 patients (83%). Sixteen patients (53%) had grade 3 to 4 treatment-related adverse events; the most common were neutropenia (n = 9), thrombocytopenia (n = 3), and peripheral neuropathy (n = 3). There were no treatment-related deaths.
CONCLUSION
In patients with R/R PMBL, the combination of nivolumab plus BV represents a promising option, with high antitumor activity and a manageable safety profile.
Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Brentuximab Vedotin; Cohort Studies; Female; Humans; Lymphoma, Large B-Cell, Diffuse; Male; Mediastinal Neoplasms; Middle Aged; Neoplasm Staging; Nivolumab; Recurrence; Young Adult
PubMed: 31398081
DOI: 10.1200/JCO.19.01492 -
The Lancet. Digital Health Sep 2023Mediastinal neoplasms are typical thoracic diseases with increasing incidence in the general global population and can lead to poor prognosis. In clinical practice, the...
BACKGROUND
Mediastinal neoplasms are typical thoracic diseases with increasing incidence in the general global population and can lead to poor prognosis. In clinical practice, the mediastinum's complex anatomic structures and intertype confusion among different mediastinal neoplasm pathologies severely hinder accurate diagnosis. To solve these difficulties, we organised a multicentre national collaboration on the basis of privacy-secured federated learning and developed CAIMEN, an efficient chest CT-based artificial intelligence (AI) mediastinal neoplasm diagnosis system.
METHODS
In this multicentre cohort study, 7825 mediastinal neoplasm cases and 796 normal controls were collected from 24 centres in China to develop CAIMEN. We further enhanced CAIMEN with several novel algorithms in a multiview, knowledge-transferred, multilevel decision-making pattern. CAIMEN was tested by internal (929 cases at 15 centres), external (1216 cases at five centres and a real-world cohort of 11 162 cases), and human-AI (60 positive cases from four centres and radiologists from 15 institutions) test sets to evaluate its detection, segmentation, and classification performance.
FINDINGS
In the external test experiments, the area under the receiver operating characteristic curve for detecting mediastinal neoplasms of CAIMEN was 0·973 (95% CI 0·969-0·977). In the real-world cohort, CAIMEN detected 13 false-negative cases confirmed by radiologists. The dice score for segmenting mediastinal neoplasms of CAIMEN was 0·765 (0·738-0·792). The mediastinal neoplasm classification top-1 and top-3 accuracy of CAIMEN were 0·523 (0·497-0·554) and 0·799 (0·778-0·822), respectively. In the human-AI test experiments, CAIMEN outperformed clinicians with top-1 and top-3 accuracy of 0·500 (0·383-0·633) and 0·800 (0·700-0·900), respectively. Meanwhile, with assistance from the computer aided diagnosis software based on CAIMEN, the 46 clinicians improved their average top-1 accuracy by 19·1% (0·345-0·411) and top-3 accuracy by 13·0% (0·545-0·616).
INTERPRETATION
For mediastinal neoplasms, CAIMEN can produce high diagnostic accuracy and assist the diagnosis of human experts, showing its potential for clinical practice.
FUNDING
National Key R&D Program of China, National Natural Science Foundation of China, and Beijing Natural Science Foundation.
Topics: Humans; Mediastinal Neoplasms; Mediastinum; Artificial Intelligence; Cohort Studies; Diagnosis, Computer-Assisted
PubMed: 37625894
DOI: 10.1016/S2589-7500(23)00106-1