-
Cancers Nov 2022Malignant Mesothelioma (MM) is an aggressive neoplasm of the pleural mesothelium, less frequently peritoneal and exceptionally of the vaginal tunic of the testicle and...
Malignant Mesothelioma (MM) is an aggressive neoplasm of the pleural mesothelium, less frequently peritoneal and exceptionally of the vaginal tunic of the testicle and pericardium [...].
PubMed: 36428633
DOI: 10.3390/cancers14225540 -
Journal For Immunotherapy of Cancer Feb 2021CD40 agonist immunotherapy can potentially license antigen-presenting cells to promote antitumor T-cell activation and re-educate macrophages to destroy tumor stroma....
BACKGROUND
CD40 agonist immunotherapy can potentially license antigen-presenting cells to promote antitumor T-cell activation and re-educate macrophages to destroy tumor stroma. Systemic administration of CD40 agonists has historically been associated with considerable toxicity, providing the rationale for development of tumor-targeted immunomodulators to improve clinical safety and efficacy. This phase I study assessed the safety, tolerability, preliminary antitumor activity, and preliminary biomarkers of ABBV-428, a first-in-class, mesothelin-targeted, bispecific antibody designed for tumor microenvironment-dependent CD40 activation with limited systemic toxicity.
METHODS
ABBV-428 was administered intravenously every 2 weeks to patients with advanced solid tumors. An accelerated titration (starting at a 0.01 mg/kg dose) and a 3+3 dose escalation scheme were used, followed by recommended phase II dose cohort expansions in ovarian cancer and mesothelioma, tumor types associated with high mesothelin expression.
RESULTS
Fifty-nine patients were treated at doses between 0.01 and 3.6 mg/kg. The maximum tolerated dose was not reached, and 3.6 mg/kg was selected as the recommended phase II dose. Seven patients (12%) reported infusion-related reactions. Treatment-related grade ≥3 treatment-emergent adverse events were pericardial effusion, colitis, infusion-related reaction, and pleural effusion (n=1 each, 2%), with no cytokine release syndrome reported. The pharmacokinetic profile demonstrated roughly dose-proportional increases in exposure from 0.4 to 3.6 mg/kg. Best response was stable disease in 9/25 patients (36%) treated at the recommended phase II dose. CD40 receptor occupancy >90% was observed on peripheral B-cells starting from 0.8 mg/kg; however, no consistent changes from baseline in intratumoral CD8+ T-cells, programmed death ligand-1 (PD-L1+) cells, or immune-related gene expression were detected post-ABBV-428 treatment (cycle 2, day 1). Mesothelin membrane staining showed greater correlation with progression-free survival in ovarian cancer and mesothelioma than in the broader dose escalation population.
CONCLUSIONS
ABBV-428 monotherapy exhibited dose-proportional pharmacokinetics and an acceptable safety profile, particularly for toxicities characteristic of CD40 agonism, illustrating that utilization of a tumor-targeted, bispecific antibody can improve the safety of CD40 agonism as a therapeutic approach. ABBV-428 monotherapy had minimal clinical activity in dose escalation and in a small expansion cohort of patients with advanced mesothelioma or ovarian cancer.
TRIAL REGISTRATION NUMBER
NCT02955251.
Topics: Adult; Aged; Aged, 80 and over; Antibodies, Bispecific; Antineoplastic Agents, Immunological; CD40 Antigens; Female; France; Humans; Male; Maximum Tolerated Dose; Mesothelin; Middle Aged; Neoplasms; Progression-Free Survival; Time Factors; Tumor Microenvironment; United States
PubMed: 33608377
DOI: 10.1136/jitc-2020-002015 -
Scandinavian Journal of Work,... Nov 2020Objectives The purposes of this study are to describe the epidemiology of pericardial and tunica vaginalis testis mesothelioma and assess the role of asbestos exposure...
Objectives The purposes of this study are to describe the epidemiology of pericardial and tunica vaginalis testis mesothelioma and assess the role of asbestos exposure for these rare diseases. Methods Based on incident pericardial and tunica vaginalis testis mesothelioma cases collected from the Italian national mesothelioma registry (ReNaM) in the period 1993-2015, incidence rates, survival median period and prognostic factors have been evaluated. A case-control study has been performed to analyze the association with asbestos exposure (occupational and non-occupational) for these diseases. Results Between 1993 and 2015, 58 pericardial (20 women and 38 men) and 80 tunica vaginalis testis mesothelioma cases have been registered with a mean annual standardized (world standard population as reference) incidence rates of 0.049 (per million) in men and 0.023 in women for the pericardial site, and 0.095 for tunica vaginalis testis mesothelioma. Occupational exposure to asbestos was significantly associated with the risk of the diseases [odds ratio (OR) 3.68, 95% confidence interval (CI) 1.85-7.31 and OR 3.42, 95% CI 1.93-6.04 in pericardial and tunica vaginalis testis mesothelioma, respectively]. The median survival was 2.5 months for pericardial and 33.0 months for tunica vaginalis testis mesotheliomas. Age was the main predictive factor for survival for both anatomical sites. Conclusions For the first time in an analytical study, asbestos exposure was associated with pericardial and tunica vaginalis testis mesothelioma risk, supporting the causal role of asbestos for all anatomical sites. The extreme rarity of the diseases, the poor survival and the prognostic role of age have been confirmed based on population and nationwide mesothelioma registry data.
Topics: Adolescent; Adult; Aged; Asbestos; Case-Control Studies; Child; Child, Preschool; Female; Humans; Incidence; Infant; Infant, Newborn; Italy; Male; Mesothelioma, Malignant; Middle Aged; Occupational Diseases; Occupational Exposure; Pericardium; Registries; Testicular Neoplasms; Young Adult
PubMed: 32253443
DOI: 10.5271/sjweh.3895 -
Cureus Nov 2021Primary pericardial mesothelioma (PPM) is an extremely rare malignancy with a very poor prognosis. It poses a diagnostic challenge given its often late and non-specific...
Primary pericardial mesothelioma (PPM) is an extremely rare malignancy with a very poor prognosis. It poses a diagnostic challenge given its often late and non-specific presentation. This report describes a 74-year-old man who presented with central pleuritic chest pain and mild breathlessness. The patient was febrile and mildly tachycardic with crepitations in the right lung base. Blood tests revealed raised inflammatory markers and chest X-ray showed no acute pathology. Following admission, CT pulmonary angiogram showed a large left-sided mediastinal mass (approximately 110 x 70 x 85 mm) centered on the pericardium. Further post venous phase CT imaging identified possible myocardial invasion alongside suspicious liver nodules. Later, outpatient fluorodeoxyglucose (FDG) positron emission tomography (PET) imaging highlighted further FDG avid pleural and liver lesions. CT-guided biopsy of the pericardial lesion was undertaken, with histology and immunohistochemistry indicating epitheliod-type mesothelioma. A significant malignant pericardial effusion was also identified, which ultimately required pericardial window formation. Immunotherapy was commenced utilizing dual nivolumab and ipilimumab, a novel regime for the treatment of mesothelioma. Palliative radiotherapy to the pericardial lesion will also be performed. Here, we demonstrate the diagnostic challenge of this vanishingly rare condition, which is usually diagnosed upon the development of associated complications. Early recognition gives the best chance of improved mortality, however, diagnosis requires a high index of clinical suspicion alongside prompt investigation, primarily involving cross-sectional imaging.
PubMed: 34984126
DOI: 10.7759/cureus.19966 -
Case Reports in Medicine 2016This case report describes a 37-year-old female who was admitted to our Emergency Department because of shortness of breath. On physical examination, she had dyspnea and...
This case report describes a 37-year-old female who was admitted to our Emergency Department because of shortness of breath. On physical examination, she had dyspnea and tachycardia and blood pressure was 80/50 mmHg with a pulsus paradoxus of 22 mmHg. Neck veins were distended, heart sounds were distant, and dullness was found on both lung bases. Her chest X-ray revealed bilateral pleural effusion and cardiomegaly. On both computed tomography and echocardiography the heart was of normal size and a large pericardial effusion was noted. The echocardiogram showed signs of impending tamponade, so the patient underwent an emergent pericardiocentesis. No infectious etiology was found and she was assumed to have viral pericarditis and was treated accordingly. However, when the pericardial effusion recurred and empirical therapy for tuberculosis failed, a pericardial window was performed. A typical staining pattern for mesothelioma was found on her pericardial biopsy specimen. Since no other mesodermal tissue was affected, a diagnosis of primary malignant pericardial mesothelioma was made. Chemotherapy was not effective and she passed away a year after the diagnosis was made. This case highlights the difficulties in diagnosing this uncommon disease in patients that present with the common finding of pericardial effusion.
PubMed: 28003826
DOI: 10.1155/2016/4810901 -
BMJ Open Aug 2021This paper aims to establish hospitalisation costs of mesothelioma in Italy and to evaluate hospital-related trends associated with the 1992 asbestos ban.
OBJECTIVES
This paper aims to establish hospitalisation costs of mesothelioma in Italy and to evaluate hospital-related trends associated with the 1992 asbestos ban.
DESIGN
This is a retrospective population-based study of Italian hospitalisations treating pleura, peritoneum and pericardium mesothelioma in the period 2001-2018.
SETTINGS
Public and private Italian hospitals reached by the Ministry of Health (coverage close to 100%).
PARTICIPANTS
157 221 admissions with primary or contributing diagnosis of pleural, peritoneal or hearth cancer discharged from 2001 to 2018.Primary and secondary outcome measures: number, length and cost of hospitalisations with related percentages.
RESULTS
Each year, Italian hospitals treated a mesothelioma in 6025 admissions on average. Mean annual costs by site were €20 293 733, €3183 632 and €40 443 for pleura, peritoneum and pericardium, respectively. Pericardial mesothelioma showed the highest cost per admission (€6117), followed by peritoneal (€4549) and pleural cases (€3809). Percentage of hospitalisation costs attributable to mesothelioma was higher when it is located in pleura (53.4%) and pericardium (51.8%) with respect to peritoneum (41.2%). Overall annual hospitalisation cost, percentages of number and length of admissions showed an inverted U-shape, with maxima (of €25 850 276, 0.064% and 0.096%, respectively) reached in 2011-2013. Mean age at discharge and percentages of surgery and of urgent cases increased over time.
CONCLUSIONS
The highest impact of mesothelioma on the National Health System was recorded 20 years after the asbestos ban (2011-2013). Hospitals should expect soon fewer but more severe patients needing more cares. To study the disease prevalence could help assistance planning of next decade.
Topics: Asbestos; Hospitalization; Hospitals; Humans; Incidence; Italy; Mesothelioma; Mesothelioma, Malignant; Occupational Exposure; Patient Discharge; Pleural Neoplasms; Registries; Retrospective Studies
PubMed: 34373297
DOI: 10.1136/bmjopen-2020-046456 -
Journal of Surgical Case Reports May 2024Pericardial mesothelioma (PM) is rare with only 200 cases recorded, and a post-mortem prevalence of <0.0022%. It is the third most common cardiac/pericardial tumour,...
Pericardial mesothelioma (PM) is rare with only 200 cases recorded, and a post-mortem prevalence of <0.0022%. It is the third most common cardiac/pericardial tumour, behind angiosarcoma and rhabdomyosarcoma. PM incidence increases with age, typically incidentally diagnosed between 50 and 70 years, with a 3:1 male predominance. Occasional PM can cause chest pain, dyspnoea, cough and even dysphagia. PMs are often misdiagnosed with only 25% of cases being antemortem diagnoses. Unlike pleural mesothelioma, the link between asbestos exposure and malignancy is less convincing, with only 20% of cases having known exposure. 6 There are three histological types: epithelioid, fibrous (spindle cell), and biphasic (mixed). The average life-expectancy post diagnosis is 3-10 months. Due to the heterogeneity of the presentation and rarity there is no standardized management algorithm, and the diagnostic imaging or laboratory investigations are scarcely described. We are presenting one of the cases diagnosed in our unit here in the Gold Coast.
PubMed: 38711818
DOI: 10.1093/jscr/rjae279 -
World Journal of Clinical Cases Nov 2022Primary malignant pericardial mesothelioma (PMPM) is an extremely rare malignant tumor, and it is difficult to diagnose definitively before death. We present a case in...
BACKGROUND
Primary malignant pericardial mesothelioma (PMPM) is an extremely rare malignant tumor, and it is difficult to diagnose definitively before death. We present a case in which PMPM was diagnosed at autopsy. We consider this case to be highly suggestive and report it here.
CASE SUMMARY
A 78-year-old male presented with transient loss of consciousness and falls. The transient loss of consciousness was considered to result from complications of diastolic dysfunction due to pericardial disease, fever with dehydration, and paroxysmal atrial fibrillation. Ultrasound cardiography (UCG) and computed tomography showed cardiac enlargement and high-density pericardial effusion. We considered pericardial disease to be the main pathogenesis of this case. Cardiac magnetic resonance imaging and gadolinium contrast-enhanced T1-weighted images showed thick staining inside and outside the pericardium. Pericardial biopsy was considered to establish a definitive diagnosis, but the patient and his family refused further treatment and examinations, and the patient was followed conservatively. We noticed a thickening of the pericardium and massive changes in the pericardium on UCG over time. We performed an autopsy 60 h after the patient died of pneumonia. Giemsa staining of the autopsy tissue showed an epithelial-like arrangement in the pericardial tumor, and immunostaining showed positive and negative factors for the diagnosis of PMPM. Based on these findings, the final diagnosis of PMPM was made.
CONCLUSION
PMPM has a poor prognosis, and early diagnosis and treatment are important. The temporal echocardiographic findings may provide a clue for the diagnosis of PMPM.
PubMed: 36483836
DOI: 10.12998/wjcc.v10.i33.12380 -
BMC Veterinary Research Jul 2023Pericardial effusions are one of the most common cardiac diseases in dogs. Common causes of haemorrhagic pericardial effusions include neoplasia, such as...
BACKGROUND
Pericardial effusions are one of the most common cardiac diseases in dogs. Common causes of haemorrhagic pericardial effusions include neoplasia, such as hemangiosarcoma, mesothelioma, chemodectoma, and ectopic thyroid tumours, and benign idiopathic pericardial effusion. Distinguishing among reactive mesothelial cells, malignant mesothelioma, and adenocarcinoma in body effusions is a diagnostic challenge. Therefore, the author aimed to discover whether the observed cells were reactive mesothelial, mesothelioma, or adenocarcinoma cells through immunocytochemistry using five markers (cytokeratin, vimentin, desmin, E-cadherin, and calretinin) in a canine patient.
CASE PRESENTATION
A 2.1 kg, spayed female, 10-year-old Yorkshire Terrier dog presented to a local hospital with dyspnoea and was evaluated for pericardial effusion. The presence of pericardial fluid was confirmed, and she was referred to our hospital for further evaluation. In cytological evaluation, cells shed individually or in clusters were observed, along with numerous non-degenerative neutrophils and macrophages. The cells showed binucleation, anisocytosis, anisokaryosis, abnormal nucleoli, abundant basophilic cytoplasm, high nuclear-cytoplasmic ratio, and coarse chromatin. Large atypical multinucleate cells were also observed. Erythrophagia was observed, indicating chronic haemorrhage. Immunocytochemistry using pericardial fluid was positive for cytokeratin, vimentin, desmin, E-cadherin, and calretinin. Therefore, malignant mesothelioma was diagnosed.
CONCLUSIONS
Immunocytochemistry is a very useful diagnostic technique because it can determine whether several fluorescent markers are simultaneously expressed in the same cell. Further, E-cadherin and calretinin can be used for the differential diagnosis of reactive mesothelial cells, malignant mesothelioma, and adenocarcinoma in dogs.
Topics: Female; Dogs; Animals; Pericardial Effusion; Pericardial Fluid; Mesothelioma, Malignant; Calbindin 2; Vimentin; Immunohistochemistry; Desmin; Thymus Neoplasms; Mesothelioma; Heart Neoplasms; Adenocarcinoma; Cadherins; Dog Diseases
PubMed: 37480011
DOI: 10.1186/s12917-023-03655-8 -
Radiologia 2021To describe the radiologic findings of extrapulmonary air in the chest and to review atypical and unusual causes of extrapulmonary air, emphasizing the importance of the... (Review)
Review
OBJECTIVE
To describe the radiologic findings of extrapulmonary air in the chest and to review atypical and unusual causes of extrapulmonary air, emphasizing the importance of the diagnosis in managing these patients.
CONCLUSION
In this article, we review a series of cases collected at our center that manifest with extrapulmonary air in the thorax, paying special attention to atypical and uncommon causes. We discuss the causes of extrapulmonary according to its location: mediastinum (spontaneous pneumomediastinum with pneumorrhachis, tracheal rupture, dehiscence of the bronchial anastomosis after lung transplantation, intramucosal esophageal dissection, Boerhaave syndrome, tracheoesophageal fistula in patients with esophageal tumors, bronchial perforation and esophagorespiratory fistula due to lymph-node rupture, and acute mediastinitis), pericardium (pneumopericardium in patients with lung tumors), cardiovascular (venous air embolism), pleura (bronchopleural fistulas, spontaneous pneumothorax in patients with malignant pleural mesotheliomas and primary lung tumors, and bilateral pneumothorax after unilateral lung biopsy), and thoracic wall (infections, transdiaphragmatic intercostal hernia, and subcutaneous emphysema after lung biopsy).
Topics: Humans; Mediastinal Emphysema; Rupture; Subcutaneous Emphysema; Thorax; Trachea
PubMed: 34246426
DOI: 10.1016/j.rxeng.2021.02.005