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Pediatric Rheumatology Online Journal Apr 2024Immune checkpoint inhibitors (ICIs) have expanded the arsenal of cancer therapeutics over the last decade but are associated with a spectrum of immune-related adverse...
BACKGROUND
Immune checkpoint inhibitors (ICIs) have expanded the arsenal of cancer therapeutics over the last decade but are associated with a spectrum of immune-related adverse events (irAEs), including inflammatory arthritis. While these complications are increasingly recognized in the adult population, no cases of inflammatory arthritis irAEs have been reported in the pediatric literature.
CASE PRESENTATION
A 14-year-old female with metastatic epithelioid mesothelioma was referred to the pediatric rheumatology clinic after developing progressive inflammatory joint pain in her bilateral shoulders, hips, and small joints of hands following the second cycle of Nivolumab and Ipilimumab. Initial examinations showed bilateral shoulder joint line tenderness, positive FABERs test bilaterally, tenderness over bilateral greater trochanters, and bilateral second PIP effusions. Her serological profile was notable for positive HLA-B27, positive anti-CCP, negative Rheumatoid Factor, and negative ANA. PET-CT scan performed for disease response following immunotherapy showed symmetric increased metabolic activity primarily involving the supraspinatus, gluteus medius and minimus, and semimembranosus tendon insertions. Her presentation was consistent with a grade 1 irAE that worsened to a grade 2 irAE despite NSAID therapy, prompting a short course of oral prednisolone. She achieved clinical remission of her mesothelioma following six cycles of Nivolumab and Ipilimumab and her inflammatory arthritis was controlled on Celebrex monotherapy.
CONCLUSIONS
To our knowledge, this is the first pediatric case of ICI-induced inflammatory arthritis and enthesitis. This case highlights the importance of increasing awareness of diagnosis and management of irAEs in children.
Topics: Humans; Ipilimumab; Female; Nivolumab; Adolescent; Immune Checkpoint Inhibitors; Arthritis; Mesothelioma, Malignant
PubMed: 38685034
DOI: 10.1186/s12969-024-00983-3 -
Cell Death & Disease Apr 2024Scientific literature supports the evidence that cancer stem cells (CSCs) retain inside low reactive oxygen species (ROS) levels and are, therefore, less susceptible to...
Scientific literature supports the evidence that cancer stem cells (CSCs) retain inside low reactive oxygen species (ROS) levels and are, therefore, less susceptible to cell death, including ferroptosis, a type of cell death dependent on iron-driven lipid peroxidation. A collection of lung adenocarcinoma (LUAD) primary cell lines derived from malignant pleural effusions (MPEs) of patients was used to obtain 3D spheroids enriched for stem-like properties. We observed that the ferroptosis inducer RSL3 triggered lipid peroxidation and cell death in LUAD cells when grown in 2D conditions; however, when grown in 3D conditions, all cell lines underwent a phenotypic switch, exhibiting substantial resistance to RSL3 and, therefore, protection against ferroptotic cell death. Interestingly, this phenomenon was reversed by disrupting 3D cells and growing them back in adherence, supporting the idea of CSCs plasticity, which holds that cancer cells have the dynamic ability to transition between a CSC state and a non-CSC state. Molecular analyses showed that ferroptosis resistance in 3D spheroids correlated with an increased expression of antioxidant genes and high levels of proteins involved in iron storage and export, indicating protection against oxidative stress and low availability of iron for the initiation of ferroptosis. Moreover, transcriptomic analyses highlighted a novel subset of genes commonly modulated in 3D spheroids and potentially capable of driving ferroptosis protection in LUAD-CSCs, thus allowing to better understand the mechanisms of CSC-mediated drug resistance in tumors.
Topics: Ferroptosis; Humans; Neoplastic Stem Cells; Adenocarcinoma of Lung; Lung Neoplasms; Spheroids, Cellular; Cell Line, Tumor; Lipid Peroxidation; Reactive Oxygen Species; Gene Expression Regulation, Neoplastic; Drug Resistance, Neoplasm; Iron
PubMed: 38684666
DOI: 10.1038/s41419-024-06667-w -
BMC Public Health Apr 2024Malignant mesothelioma is a rare form of cancer that mostly affects the pleura and has a strong link to asbestos exposure. Greece banned the use of asbestos in 2005,...
BACKGROUND
Malignant mesothelioma is a rare form of cancer that mostly affects the pleura and has a strong link to asbestos exposure. Greece banned the use of asbestos in 2005, however, the public was already aware of this substance in the 1980s. This research aims to present an overview of Greece's mesothelioma age-standardized mortality rates (ASMR) from 1983 to 2019 by age, gender, and geographic region and to determine whether the actions to ban asbestos impacted these rates.
METHODS
Data were retrieved by the Hellenic Statistical Authority (HSA) from death certificates that mentioned mesothelioma as the cause of death from 1983 to 2019 with details on the residence, gender, and age. Statistical analysis was performed using PRISM 6.0 software, a two-way ANOVA test, Trend analysis was conducted using Joinpoint Regression Program 5.0 software. The linear and non-linear model was used to calculate the age-standardized rates of annual percentage change (APC) and its 95% confidential interval (95% CI).
RESULTS
From 1983 to 2019, 850 total mesothelioma deaths were recorded, the majority of whom were males (634). A rate of 74.6% accounts for males and 25.4% for females, and the ratio of Males: Females was 3:1. Males' ASMR and the whole population's ASMR reached their highest levels in 2011 (0.93/100000person-years and 0.53/100000person-years, respectively). To look for potential changes between the first two decades of the 21st century, we compared the mean ASMR of each geographic region in Greece between two different 10-year subperiods (2000-2009 and 2010-2019). Except for Epirus, all regions of Greece had elevated regional ASMRs, particularly in those with the highest asbestos deposits. Notably, the ASMR in Epirus decreased from 0.54/100000person-years (2000-2009) to 0.31/100000person-years (2010-2019). After 2011, the ASMR for men and the general population stabilized. This stability is important since mesothelioma in men is associated with occupational asbestos exposure. The intriguing discovery of a lower ASMR in Epirus emphasizes the need to raise awareness of the condition and implement effective public health measures.
CONCLUSIONS
In Greece, the annual ASMR for males and the whole population reached its highest level in 2011, which is positive and encouraging and may be a sign that the rate will stabilize during the following years. Moreover, this study showed that the actions made in the 1980s regarding public awareness and surveillance directly impacted the decrease in Epirus rates. Future research, continual awareness, information, and recording are needed to monitor the mesothelioma epidemic. The possible benefit of a mesothelioma registry and the epidemiological surveillance of asbestos-related diseases, particularly mesothelioma mortality, need to be addressed.
TRIAL REGISTRATION
Not applicable.
Topics: Humans; Greece; Male; Female; Asbestos; Mesothelioma; Middle Aged; Aged; Adult; Mesothelioma, Malignant; Aged, 80 and over; Environmental Exposure; Lung Neoplasms
PubMed: 38671450
DOI: 10.1186/s12889-024-18030-x -
Medicine Apr 2024Malignant peritoneal mesothelioma (MPM) is a rare clinical disease. Although there are several reports describing intraperitoneal mesothelioma of the lung, liver, and...
RATIONALE
Malignant peritoneal mesothelioma (MPM) is a rare clinical disease. Although there are several reports describing intraperitoneal mesothelioma of the lung, liver, and intestine, retroperitoneal mesothelioma is, to our knowledge, very rare and rarely reported. In recent years, our best clinical protocols for the treatment and diagnosis of retroperitoneal mesothelioma have not been proven and the diagnosis and treatment are challenging.
PATIENT CONCERNS
A 37-year-old Chinese woman complained of bilateral low back pain for a month, with obvious symptoms of low back pain on the left side. To treat low back pain, retroperitoneal masses were found during physical examination. The patient consulted a urological specialist for further treatment.
DIAGNOSIS
After the operation, pathological biopsy confirmed retroperitoneal epithelioid diffuse mesothelioma.
INTERVENTIONS
After exclusion of surgical contraindications, the patient underwent laparoscopic retroperitoneal lesion resection under tracheal intubation and general anesthesia, and the operation was successful.
OUTCOMES
On the tenth day after surgery, the patient vital signs were stable, and he was discharged.
LESSONS
Patients with malignant peritoneal mesothelioma may have no typical clinical symptoms, and the diagnosis is based on pathological and immunohistochemical examination. In selected patients, surgical cell reduction and intraoperative intraperitoneal heat chemotherapy have become the first choice of treatment, which can achieve ideal therapeutic effects and prolong survival.
Topics: Humans; Adult; Female; Retroperitoneal Neoplasms; Mesothelioma, Malignant; Mesothelioma; Peritoneal Neoplasms; Lung Neoplasms; Laparoscopy
PubMed: 38669368
DOI: 10.1097/MD.0000000000037985 -
Current Oncology (Toronto, Ont.) Apr 2024Maintenance chemotherapy is a standard treatment in patients with non-progressive advance staged IV non-squamous non-small cell lung cancer after induction therapy....
Maintenance chemotherapy is a standard treatment in patients with non-progressive advance staged IV non-squamous non-small cell lung cancer after induction therapy. Here, we report the case of a 53-year-old man undergoing a maintenance monotherapy with pemetrexed who presented prolonged pancytopenia despite filgrastim injections. A bone marrow aspiration revealed a macrophage activation syndrome with amastigotes. A Polymerase Chest Reaction testing confirmed the diagnosis of visceral leishmaniasis. Treatment with liposomal amphotericin B was started. Oncologists should bear in mind that visceral leishmaniasis in endemic areas can potentially induce severe and prolonged pancytopenia in immunosuppressed patients, during chemotherapy in particular.
Topics: Humans; Pancytopenia; Leishmaniasis, Visceral; Male; Middle Aged; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Diagnosis, Differential; Pemetrexed; Antineoplastic Agents; Antiprotozoal Agents; Amphotericin B
PubMed: 38668071
DOI: 10.3390/curroncol31040168 -
Sao Paulo Medical Journal = Revista... 2024There is still a debate regarding the most appropriate pleural collector model to ensure a short hospital stay and minimum complications. (Randomized Controlled Trial)
Randomized Controlled Trial Comparative Study
BACKGROUND
There is still a debate regarding the most appropriate pleural collector model to ensure a short hospital stay and minimum complications.
OBJECTIVES
To study aimed to compare the time of air leak, time to drain removal, and length of hospital stay between a standard water-seal drainage system and a pleural collector system with a unidirectional flutter valve and rigid chamber.
DESIGN AND SETTING
A randomized prospective clinical trial was conducted at a high-complexity hospital in São Paulo, Brazil.
METHODS
Sixty-three patients who underwent open or video-assisted thoracoscopic lung wedge resection or lobectomy were randomized into two groups, according to the drainage system used: the control group (WS), which used a conventional water-seal pleural collector, and the study group (V), which used a flutter valve device (Sinapi® Model XL1000®). Variables related to the drainage system, time of air leak, time to drain removal, and time spent in hospital were compared between the groups.
RESULTS
Most patients (63%) had lung cancer. No differences were observed between the groups in the time of air leak or time spent hospitalized. The time to drain removal was slightly shorter in the V group; however, the difference was not statistically significant. Seven patients presented with surgery-related complications: five and two in the WS and V groups, respectively.
CONCLUSIONS
Air leak, time to drain removal, and time spent in the hospital were similar between the groups. The system used in the V group resulted in no adverse events and was safe.
REGISTRATION
RBR-85qq6jc (https://ensaiosclinicos.gov.br/rg/RBR-85qq6jc).
Topics: Humans; Male; Female; Prospective Studies; Middle Aged; Drainage; Pneumonectomy; Aged; Length of Stay; Thoracic Surgery, Video-Assisted; Time Factors; Treatment Outcome; Lung Neoplasms; Adult; Equipment Design; Postoperative Complications
PubMed: 38655983
DOI: 10.1590/1516-3180.2023.0224.R1.08022024 -
Cancer Research Communications May 2024Cancer-induced skeletal muscle defects differ in severity between individuals with the same cancer type. Cancer subtype-specific genomic aberrations are suggested to...
UNLABELLED
Cancer-induced skeletal muscle defects differ in severity between individuals with the same cancer type. Cancer subtype-specific genomic aberrations are suggested to mediate these differences, but experimental validation studies are very limited. We utilized three different breast cancer patient-derived xenograft (PDX) models to correlate cancer subtype with skeletal muscle defects. PDXs were derived from brain metastasis of triple-negative breast cancer (TNBC), estrogen receptor-positive/progesterone receptor-positive (ER+/PR+) primary breast cancer from a BRCA2-mutation carrier, and pleural effusion from an ER+/PR- breast cancer. While impaired skeletal muscle function as measured through rotarod performance and reduced levels of circulating and/or skeletal muscle miR-486 were common across all three PDXs, only TNBC-derived PDX activated phospho-p38 in skeletal muscle. To further extend these results, we generated transformed variants of human primary breast epithelial cells from healthy donors using HRASG12V or PIK3CAH1047R mutant oncogenes. Mutations in RAS oncogene or its modulators are found in approximately 37% of metastatic breast cancers, which is often associated with skeletal muscle defects. Although cells transformed with both oncogenes generated adenocarcinomas in NSG mice, only HRASG12V-derived tumors caused skeletal muscle defects affecting rotarod performance, skeletal muscle contraction force, and miR-486, Pax7, pAKT, and p53 levels in skeletal muscle. Circulating levels of the chemokine CXCL1 were elevated only in animals with tumors containing HRASG12V mutation. Because RAS pathway aberrations are found in 19% of cancers, evaluating skeletal muscle defects in the context of genomic aberrations in cancers, particularly RAS pathway mutations, may accelerate development of therapeutic modalities to overcome cancer-induced systemic effects.
SIGNIFICANCE
Mutant RAS- and PIK3CA-driven breast cancers distinctly affect the function of skeletal muscle. Therefore, research and therapeutic targeting of cancer-induced systemic effects need to take aberrant cancer genome into consideration.
Topics: Humans; Female; Animals; Muscle, Skeletal; Mice; Breast Neoplasms; Mutation; Triple Negative Breast Neoplasms
PubMed: 38651826
DOI: 10.1158/2767-9764.CRC-24-0045 -
Clinical and Experimental Medicine Apr 2024Peritoneal mesothelioma (PeM) is an aggressive tumor with limited treatment options. The current study aimed to evaluate the value of next generation sequencing (NGS) of...
Peritoneal mesothelioma (PeM) is an aggressive tumor with limited treatment options. The current study aimed to evaluate the value of next generation sequencing (NGS) of PeM samples in current practice. Foundation Medicine F1CDx NGS was performed on 20 tumor samples. This platform assesses 360 commonly somatically mutated genes in solid tumors and provides a genomic signature. Based on the detected mutations, potentially effective targeted therapies were identified. NGS was successful in 19 cases. Tumor mutational burden (TMB) was low in 10 cases, and 11 cases were microsatellite stable. In the other cases, TMB and microsatellite status could not be determined. BRCA1 associated protein 1 (BAP1) mutations were found in 32% of cases, cyclin dependent kinase inhibitor 2A/B (CDKN2A/B) and neurofibromin 2 (NF2) mutations in 16%, and ataxia-telangiectasia mutated serine/threonine kinase (ATM) in 11%. Based on mutations in the latter two genes, potential targeted therapies are available for approximately a quarter of cases (i.e., protein kinase inhibitors for three NF2 mutated tumors, and polyADP-ribose polymerase inhibitors for two ATM mutated tumors). Extensive NGS analysis of PeM samples resulted in the identification of potentially effective targeted therapies for about one in four patients. Although these therapies are currently not available for patients with PeM, ongoing developments might result in new treatment options in the future.
Topics: Humans; Mesothelioma; Lung Neoplasms; Mesothelioma, Malignant; Mutation; Genomics; Biomarkers, Tumor; Peritoneal Neoplasms
PubMed: 38642130
DOI: 10.1007/s10238-024-01342-y -
European Journal of Cardio-thoracic... Mar 2024Postoperative empyema is a severe, potentially lethal complication also present, but poorly studied in patients undergoing surgery for pleural mesothelioma. We aimed to...
OBJECTIVES
Postoperative empyema is a severe, potentially lethal complication also present, but poorly studied in patients undergoing surgery for pleural mesothelioma. We aimed to analyse which perioperative characteristics might be associated with an increased risk for postoperative empyema.
METHODS
From September 1999 to February 2023 a retrospective analysis of consecutive patients undergoing surgery for pleural mesothelioma at the University Hospital of Zurich was performed. Uni- and multivariable logistic regression was used to identify associated risk factors of postoperative empyema after surgery.
RESULTS
A total of 400 PM patients were included in the analysis, of which n = 50 patients developed empyema after surgery (12.5%). Baseline demographics were comparable between patients with (Eyes) and without empyema (Eno). 39% (n = 156) patients underwent extrapleural pneumonectomy (EPP), of whom 22% (n = 35) developed postoperative pleural empyema; 6% (n = 15) of the remaining 244 patients undergoing pleurectomy and decortication (n = 46), extended pleurectomy and decortication (n = 114), partial pleurectomy (n = 54) or explorative thoracotomy (n = 30) resulted in postoperative empyema. In multivariable logistic regression analysis, EPP (odds ratio 2.8, 95% confidence interval 1.5-5.4, P = 0.002) emerged as the only risk factor associated with postoperative empyema when controlled for smoking status. Median overall survival was significantly worse for Eyes (16 months, interquartile range 5-27 months) than for Eno (18 months, interquartile range 8-35 months).
CONCLUSIONS
Patients undergoing EPP had a significantly higher risk of developing postoperative pleural empyema compared to patients undergoing other surgery types. Survival of patients with empyema was significantly shorter.
Topics: Humans; Male; Retrospective Studies; Female; Empyema, Pleural; Risk Factors; Aged; Pleural Neoplasms; Postoperative Complications; Middle Aged; Pneumonectomy; Mesothelioma; Mesothelioma, Malignant; Lung Neoplasms
PubMed: 38637940
DOI: 10.1093/ejcts/ezae137