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The Journal of Clinical Investigation Apr 2024Cancer-derived small extracellular vesicles (sEVs) are capable of modifying the tumor microenvironment and promoting tumor progression. Ovarian cancer (OvCa) is a lethal... (Observational Study)
Observational Study Clinical Trial
Cancer-derived small extracellular vesicles (sEVs) are capable of modifying the tumor microenvironment and promoting tumor progression. Ovarian cancer (OvCa) is a lethal malignancy that preferentially spreads through the abdominal cavity. Thus, the secretion of such vesicles into the peritoneal fluid could be a determinant factor in the dissemination and behavior of this disease. We designed a prospective observational study to assess the impact of peritoneal fluid-derived sEVs (PFD-sEVs) in OvCa clinical outcome. For this purpose, 2 patient cohorts were enrolled: patients with OvCa who underwent a diagnostic or cytoreductive surgery and nononcological patients, who underwent abdominal surgery for benign gynecological conditions and acted as the control group. Systematic extraction of PFD-sEVs from surgical samples enabled us to observe significant quantitative and qualitative differences associated with cancer diagnosis, disease stage, and platinum chemosensitivity. Proteomic profiling of PFD-sEVs led to the identification of molecular pathways and proteins of interest and to the biological validation of S100A4 and STX5. In addition, unsupervised analysis of PFD-sEV proteomic profiles in high-grade serous ovarian carcinomas (HGSOCs) revealed 2 clusters with different outcomes in terms of overall survival. In conclusion, comprehensive characterization of PFD-sEV content provided a prognostic value with potential implications in HGSOC clinical management.
Topics: Humans; Female; Ovarian Neoplasms; Extracellular Vesicles; Ascitic Fluid; Middle Aged; Proteomics; Aged; Prospective Studies; Neoplasm Proteins; Adult
PubMed: 38564289
DOI: 10.1172/JCI176161 -
Journal of Clinical and Experimental... 2024We report the case of a 52-year-old male who presented to our hospital with cervical lymphadenopathy. Lymph node biopsy revealed small atypical lymphoid cells positive...
We report the case of a 52-year-old male who presented to our hospital with cervical lymphadenopathy. Lymph node biopsy revealed small atypical lymphoid cells positive for CD3 and CD5 and negative for CD56 and Epstein-Barr virus (EBV)-encoded small RNA (EBER) by in situ hybridization. CD4-positive cells and CD8-positive cells were mixed in almost equal numbers. He was diagnosed with peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS). The patient received one cycle of chemotherapy, resulting in severe sepsis. While undergoing treatment in the intensive care unit with an antimicrobial agent and prednisone, ascitic fluid appeared. Abdominal aspiration revealed neutrophil-predominant ascites and microbiological studies revealed Candida albicans. However, ascites did not improve when treated with micafungin for Candida peritonitis. Abdominal aspiration was re-performed, and atypical lymphoid cells that were positive for CD3 and CD56 were detected. EBV-DNA levels in whole blood were significantly elevated. Atypical lymphoid cells were positive for EBER by in situ hybridization and Southern blot analysis showed EBV terminal repeat monoclonal patterns. Bone marrow examination revealed the same atypical lymphoid cells. Therefore, the patient was diagnosed with extranodal natural killer/T-cell lymphoma (ENKTL) with bone marrow involvement 3 months after the diagnosis of PTCL-NOS. Complications associated with PTCL-NOS and ENKTL are rare. PTCL-NOS, chemotherapy, sepsis, and prednisone might have led to immunodeficiency and reactivation of EBV, which might be one of the pathophysiologies for developing ENKTL. Our case indicates that measuring EBV-DNA in the blood is a simple and prompt examination to detect complications of EBV-associated lymphoma.
Topics: Male; Humans; Middle Aged; Epstein-Barr Virus Infections; Herpesvirus 4, Human; Lymphoma, T-Cell, Peripheral; Prednisone; Lymphoma, Extranodal NK-T-Cell; Ascites; Killer Cells, Natural; DNA
PubMed: 38538319
DOI: 10.3960/jslrt.23049 -
European Journal of Obstetrics,... May 2024Many patients with Essure® implant may experience adverse events related to the device. Although local inflammation does not appear to be the pathophysiological...
OBJECTIVE(S)
Many patients with Essure® implant may experience adverse events related to the device. Although local inflammation does not appear to be the pathophysiological mechanism underlying the symptoms, systemic inflammation could play a role. In the present study, as cytokines are involved in the inflammatory process, we proposed to investigate the profile of circulating and peritoneal cytokines.
STUDY DESIGN
In this retrospective study, we evaluated the levels of cytokines in peritoneal fluid (PF) as well as in plasma sample from three different groups: Essure® group, endometriosis group (known to be associated with immune dysregulation), and control group.
RESULTS
There were 60 symptomatic patients with Essure® device, 30 patients with endometriosis and a control group of 30 patients. The PF levels of Interleukin-10 (IL-10), Interleukin-6 (IL-6), and Monocyte chemoattractant protein-1 (MCP-1) were statistically higher in endometriosis group than in Essure® group and control group. The plasma level of MCP-1 was higher in Essure® group than in endometriosis group and control group. The plasma level of TNF-α was higher in Essure® group than in control group.
CONCLUSIONS
The chemokine MCP-1 as well as the pro-inflammatory TNF-α, are known to be increased in patients with fibromyalgia and chronic fatigue syndrome. Since patients with Essure® may exhibit symptoms similar to fibromyalgia, MCP-1 and TNF-α may be relevant markers in symptomatic patients with Essure®. Because of the lack of longitudinal data (no evaluation of postoperative cytokine profile and no assessment of the level of clinical improvement), other studies are needed to confirm these preliminary results.
Topics: Female; Humans; Tumor Necrosis Factor-alpha; Endometriosis; Retrospective Studies; Ascitic Fluid; Fibromyalgia; Cytokines; Interleukin-6; Inflammation
PubMed: 38537321
DOI: 10.1016/j.ejogrb.2024.03.031 -
Journal of the American Society of... 2024The diagnosis of mesothelioma has historically been challenging, especially on serous fluid cytology (SFC). Distinguishing between reactive and neoplastic mesothelial...
INTRODUCTION
The diagnosis of mesothelioma has historically been challenging, especially on serous fluid cytology (SFC). Distinguishing between reactive and neoplastic mesothelial cells can be difficult on cytomorphology alone. However, additional ancillary tests, such as BRCA1 associated protein-1 immunohistochemistry and fluorescence in situ hybridization for cyclin-dependent kinase inhibitor 2A deletion, can provide a sensitive and highly specific method of proving malignancy.
MATERIALS AND METHODS
SFC specimens diagnosed as mesothelioma, suspicious for mesothelioma (SM), and atypical mesothelial cells (AMCs) since 2012 were identified by querying the laboratory information system. Clinical data and pathologic parameters were gathered.
RESULTS
One hundred ten cases of mesothelioma, SM, and AMC were identified. Of these, 61 cases had a definitive diagnosis of mesothelioma on SFC. Average age at SFC diagnosis was 67 years (26-87 years), with most patients being male (67%). Out of the 61 cases, 11 cases (18%) had an initial diagnosis of mesothelioma made on SFC specimens, with 5 of these 11 cases being in patients that never received a histologic diagnosis of mesothelioma. Ancillary studies were utilized in all 11 cases. An initial diagnosis of metastatic mesothelioma was made on SFC in 9 cases (15%). For 6 of these 9 cases, the SFC diagnosis was the sole diagnosis of metastatic mesothelioma without a companion histologic diagnosis. In addition, 15 cases were diagnosed as SM, with 11 of these cases following a definitive mesothelioma diagnosis. Thirty-four cases were diagnosed as AMC, with 27 cases following a definitive mesothelioma diagnosis.
CONCLUSIONS
The diagnosis of mesothelioma can be reliably made on SFC with the appropriate cytomorphology criteria and/or confirmatory ancillary testing.
Topics: Humans; Male; Female; Aged; Mesothelioma; Middle Aged; Aged, 80 and over; Adult; Cytodiagnosis; Biomarkers, Tumor; Immunohistochemistry; Mesothelioma, Malignant; In Situ Hybridization, Fluorescence; Lung Neoplasms; Diagnosis, Differential; Ascitic Fluid; Pleural Effusion, Malignant; Cytology; Tumor Suppressor Proteins; Ubiquitin Thiolesterase
PubMed: 38514361
DOI: 10.1016/j.jasc.2024.02.006 -
Indian Journal of Surgical Oncology Mar 2024Peritoneal malignant mesothelioma is an uncommon neoplasm with a poor prognosis. We hereby report a case of a 20-year-old male, first diagnosed on biopsy with axillary...
Peritoneal malignant mesothelioma is an uncommon neoplasm with a poor prognosis. We hereby report a case of a 20-year-old male, first diagnosed on biopsy with axillary lymph node metastasis. He presented with abdominal pain and axillary lymphadenopathy, with no history of asbestos exposure. CECT showed peritoneal thickening and ascites. Ascitic fluid cytology showed reactive morphology. The diagnosis of metastatic deposits of malignant mesothelioma was made on histopathology and confirmed by immunohistochemistry. Tumor cells were immune-reactive for CK 5/6, calretinin, D2-40, and WT1 and negative for TTF1, CK 20, and CD 3. This case report has two important highlights-(i) unusual presentation with axillary lymph node metastasis leading to diagnostic dilemma in a young male with no asbestos exposure history and (ii) confirmatory diagnostic role of IHC in Peritoneal malignant mesothelioma.
PubMed: 38511037
DOI: 10.1007/s13193-023-01838-1 -
Journal of Reproductive Immunology Jun 2024Epithelial ovarian cancer (OC) is the deadliest female reproductive cancer; an estimated 13,270 women will die from OC in 2023. Platinum-based chemotherapy resistance...
Epithelial ovarian cancer (OC) is the deadliest female reproductive cancer; an estimated 13,270 women will die from OC in 2023. Platinum-based chemotherapy resistance mechanisms contribute to poor OC 5-year survival rates. Peripheral inflammation is linked to various disease states and we previously identified unique peritoneal microbial features predictive of OC. We hypothesized that unique peripheral immune profiles and peritoneal microbial features may be predictive of disease-free interval (time to recurrence) and response to chemotherapy in participants with OC. We also investigated self-rated health (SRH) scores in the context of peripheral inflammation as a potential screening tool for OC. Blood and peritoneal fluid were collected from participants with OC or a benign adnexal mass (BPM). Lymphocyte populations were analyzed using Fluorescence Activated Cell Sorting, serum cytokine levels were analyzed using the Human Th17 Magnetic Bead Panel assay and peritoneal fluid microbial features were analyzed using Next Generation Sequencing (NGS). Participants completed a standardized questionnaire on self-rated physical and emotional health. Participants were classified into three chemotherapy response categories: platinum-refractory, platinum-resistant or platinum-sensitive. A significant positive correlation was found between elevated inflammatory status on the day of surgery and longer disease-free interval. SRH measures did not correlate with immune status in participants with OC or a BPM. We identified a correlation between peritoneal microbial features and chemotherapy response. We conclude that immune dysbiosis may be useful in predicting OC recurrence. The immune findings reported here set the framework for additional studies utilizing immune profiles to predict platinum-based chemotherapy responsiveness in OC.
Topics: Humans; Female; Middle Aged; Dysbiosis; Adult; Carcinoma, Ovarian Epithelial; Aged; Ovarian Neoplasms; Drug Resistance, Neoplasm; Prognosis; Microbiota; Cytokines; Ascitic Fluid
PubMed: 38492533
DOI: 10.1016/j.jri.2024.104241 -
Journal of Extracellular Vesicles Mar 2024High-grade serous carcinoma of the ovary, fallopian tube and peritoneum (HGSC), the most common type of ovarian cancer, ranks among the deadliest malignancies. Many HGSC...
High-grade serous carcinoma of the ovary, fallopian tube and peritoneum (HGSC), the most common type of ovarian cancer, ranks among the deadliest malignancies. Many HGSC patients have excess fluid in the peritoneum called ascites. Ascites is a tumour microenvironment (TME) containing various cells, proteins and extracellular vesicles (EVs). We isolated EVs from patients' ascites by orthogonal methods and analyzed them by mass spectrometry. We identified not only a set of 'core ascitic EV-associated proteins' but also defined their subset unique to HGSC ascites. Using single-cell RNA sequencing data, we mapped the origin of HGSC-specific EVs to different types of cells present in ascites. Surprisingly, EVs did not come predominantly from tumour cells but from non-malignant cell types such as macrophages and fibroblasts. Flow cytometry of ascitic cells in combination with analysis of EV protein composition in matched samples showed that analysis of cell type-specific EV markers in HGSC has more substantial prognostic potential than analysis of ascitic cells. To conclude, we provide evidence that proteomic analysis of EVs can define the cellular composition of HGSC TME. This finding opens numerous avenues both for a better understanding of EV's role in tumour promotion/prevention and for improved HGSC diagnostics.
Topics: Humans; Female; Ascites; Tumor Microenvironment; Proteomics; Cystadenocarcinoma, Serous; Extracellular Vesicles; Ovarian Neoplasms
PubMed: 38490958
DOI: 10.1002/jev2.12420 -
Frontline Gastroenterology Mar 2024Using quality improvement techniques, we aimed to improve the rate of assessment and sampling of ascitic fluid for the purpose of diagnosing spontaneous bacterial...
OBJECTIVE
Using quality improvement techniques, we aimed to improve the rate of assessment and sampling of ascitic fluid for the purpose of diagnosing spontaneous bacterial peritonitis in patients with cirrhosis admitted to the hospitalist service of our institution.
DESIGN/METHODS
Based on stakeholder needs assessment, we implemented interventions targeting provider knowledge, procedure workflows and clinical decision support. We analysed key metrics during preintervention (September-December 2020), intervention roll-out (January-April 2021), postintervention (May-September 2021) and sustainability (September-December 2022) periods for admissions of patients with cirrhosis to our hospitalist service at Maine Medical Center, a 700-bed tertiary-care academic hospital in Portland, Maine, USA.
RESULTS
Among patients with cirrhosis admitted to our service, documentation of assessment for paracentesis increased from a preintervention baseline of 60.1% to 93.5% (p<0.005) postintervention. For patients with ascites potentially amenable to paracentesis, diagnostic paracentesis rate increased from 59.7% to 93% (p<0.005), with the rate of paracentesis within 24 hours increasing from 52.6% to 77.2% (p=0.01). These improvements persisted during our sustainability period. Complication rate was low (1.2%) across all study periods.
CONCLUSION
Our quality improvement project led to a sustained improvement in the identification of patients with cirrhosis needing diagnostic paracentesis and an increased procedure completion rate. This improvement strategy serves as a model for needed work toward closing a national performance gap for patients with cirrhosis.
PubMed: 38486668
DOI: 10.1136/flgastro-2023-102531 -
Journal of Community Hospital Internal... 2024Mycobacterium avium complex (MAC) infections can present as a variety of severe diseases. While it has a predilection for immunocompromised patients such as those with...
Mycobacterium avium complex (MAC) infections can present as a variety of severe diseases. While it has a predilection for immunocompromised patients such as those with Human immunodeficiency virus (HIV), it can also affect immunocompetent patients as well. One of the rare yet severe diseases that MAC infections can present is MAC peritonitis. Often hard to distinguish from other causes of peritonitis, high clinical suspicion should be maintained for those who are susceptible. Here we present an 85-year-old female with a past medical history of end-stage renal disease on peritoneal dialysis who presented with nausea and vomiting. She was found to have tenderness around her peritoneal dialysis site and was noted to have mild ascites. Her labs were significant for several electrolyte abnormalities, leukocytosis, and ascitic fluid obtained during a previous admission, and serology was positive for acid-fast bacilli. It was further revealed that the species was Mycobacterium avium complex. Initially, she started on rifampin, isoniazid, pyrazinamide, and ethambutol (RIPE), subsequently antibiotics were changed to azithromycin, ethambutol, and rifampin after MAC identification in acid-fast bacilli culture. We aim to highlight this rare presentation of peritonitis secondary to MAC.
PubMed: 38482083
DOI: 10.55729/2000-9666.1300 -
International Journal of Molecular... Feb 2024Spontaneous bacterial peritonitis (SBP) is a severe complication in patients with decompensated liver cirrhosis and is commonly treated with broad spectrum antibiotics....
Spontaneous bacterial peritonitis (SBP) is a severe complication in patients with decompensated liver cirrhosis and is commonly treated with broad spectrum antibiotics. However, the rise of antibiotic resistance requires alternative therapeutic strategies. As recently shown, human amnion-derived mesenchymal stem cells (hA-MSCs) are able, in vitro, to promote bacterial clearance and modulate the immune and inflammatory response in SBP. Our results highlight the upregulation of FOXO1, CXCL5, CXCL6, CCL20, and MAPK13 in hA-MSCs as well as the promotion of bacterial clearance, prompting a shift in the immune response toward a Th17 lymphocyte phenotype after 72 h treatment. In this study, we used an in vitro SBP model and employed omics techniques (next-generation sequencing) to investigate the mechanisms by which hA-MSCs modify the crosstalk between immune cells in LPS-stimulated ascitic fluid. We also validated the data obtained via qRT-PCR, cytofluorimetric analysis, and Luminex assay. These findings provide further support to the hope of using hA-MSCs for the prevention and treatment of infective diseases, such as SBP, offering a viable alternative to antibiotic therapy.
Topics: Humans; Ascites; Lipopolysaccharides; Amnion; Liver Cirrhosis; Ascitic Fluid; Anti-Bacterial Agents; Peritonitis; Bacterial Infections; Forkhead Box Protein O1
PubMed: 38474048
DOI: 10.3390/ijms25052801