RESUMEN
Eosinophilic gastroenteritis poses a significant diagnostic challenge, particularly in developing countries, where the awareness of this condition may be limited. Here, the case of a patient in her early 30s, who presented with recurrent episodes of abdominal pain and diarrhea, is reported. Initial standard laboratory investigations revealed normal complete blood counts and elevated total serum immunoglobulin E levels. Upper and lower endoscopic evaluations with systemic biopsies did not reveal any significant abnormalities. However, computed tomography revealed a thickened small intestine wall, halo signs, and mild ascites. Analysis of the ascitic fluid confirmed eosinophilia. These findings prompted a diagnosis of eosinophilic gastroenteritis. The patient responded well to a targeted elimination diet, corticosteroids, and antileukotriene medication. The present case emphasizes the importance of considering eosinophilic gastroenteritis in the differential diagnosis of patients who present with abdominal pain and eosinophilic ascites.
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Ascitis , Enteritis , Eosinofilia , Gastritis , Humanos , Eosinofilia/diagnóstico , Eosinofilia/patología , Ascitis/diagnóstico , Ascitis/patología , Ascitis/etiología , Femenino , Enteritis/diagnóstico , Enteritis/patología , Vietnam , Gastritis/diagnóstico , Gastritis/patología , Gastritis/complicaciones , Adulto , Tomografía Computarizada por Rayos X , Dolor Abdominal/etiología , Dolor Abdominal/diagnóstico , Diagnóstico DiferencialRESUMEN
Malignant ascites effusion (MAE) is a common complication of advanced malignant tumors with limited treatments. Euphorbia lathyris (EL) has a long history of application in patients with edema and ascites. Herein, we reported for the first time a mode in which EL and EL Pulveratum (PEL) spontaneously formed natural microemulsions (ELM and PELM) without the addition of any carriers and excipients, and found that the protein and phospholipid contained in them encapsulated fatty oil and diterpenoid esters through non-covalent interactions. The denaturation and degradation of protein in PELM resulted in stronger binding of diterpenoid esters to the hydrophobic region of protein, which facilitated the sustained and slow release of diterpenoid esters and improved their bioavailability in vivo, thereby retaining the efficacy of preventing MAE while alleviating the irritation of intestinal mucosa. The mechanism by which PELM retained efficacy might be related to increased feces moisture and urine volume, and decreased expression of AVPR2, cAMP, PKA and AQP3 in MAE mice. And its mechanism of reducing intestinal mucosal irritation was related to decreased cell apoptosis, amelioration of oxidative stress, elevation of mitochondrial membrane potential, and up-regulation of Occludin and Claudin-1 expression in IEC-6 cells. This nano-adjuvant-free natural microemulsions may be a promising therapeutic strategy in the field of phytochemistry for promoting the application of natural and efficient nano-aggregates spontaneously formed by medicinal plants in MAE, and provide a new perspective for advancing the development of the fusion of Chinese herbal medicine and nanomedicine and its clinical translation.
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Emulsiones , Euphorbia , Mucosa Intestinal , Euphorbia/química , Animales , Ratones , Mucosa Intestinal/efectos de los fármacos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patología , Ascitis/tratamiento farmacológico , Ascitis/patología , Masculino , Apoptosis/efectos de los fármacos , Extractos Vegetales/farmacología , Estrés Oxidativo/efectos de los fármacosRESUMEN
INTRODUCTION: We aimed to demonstrate the sensitivity of frozen section for patients with adult granulosa cell tumor (AGCT) and analyze the clinico-pathological factors that may be associated with sensitivity. MATERIAL METHODS: This is a multicenter study including data of 10 Gynecological Oncology Departments. Frozen-section results of patients who had ovarian AGCT at the final pathology report were retrospectively analyzed. The relation between clinico-pathological characteristics such as age, tumor size, Ca-125 level, presence of ascites, omental metastasis, menopausal status and peritoneal cytology, and the sensitivity of frozen section in patients with AGCT were evaluated. The sensitivity of frozen section diagnosis was determined by comparing the frozen section result with the final pathological diagnosis. RESULTS: Frozen section results of 274 patients with AGCT were obtained. The median age of the patients was 52 years (range, 17-82 years). Totally, 144 (52.7%, n = 273) patients were postmenopausal. The median tumour size was 90 mm (range, 9-700 mm). The median preoperative Ca-125 level was 23 IU/mL (range, 2-995 IU/mL). The sensitivity of frozen section for detecting AGCT was 76.3%. Any association between the sensitivity of frozen section and menopausal status, presence of ascites, positive cytology, omental metastasis, tumor size, Ca-125 level, age could not be shown. CONCLUSION: It is important to know the diagnosis of AGCT intraoperatively, and we demonstrated the sensitivity of frozen-section for these tumors as 76.3%.
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Antígeno Ca-125 , Secciones por Congelación , Tumor de Células de la Granulosa , Neoplasias Ováricas , Sensibilidad y Especificidad , Humanos , Femenino , Tumor de Células de la Granulosa/patología , Tumor de Células de la Granulosa/sangre , Adulto , Persona de Mediana Edad , Anciano , Estudios Retrospectivos , Adolescente , Adulto Joven , Anciano de 80 o más Años , Neoplasias Ováricas/patología , Neoplasias Ováricas/sangre , Antígeno Ca-125/sangre , Ascitis/patologíaRESUMEN
At least one-third of patients with epithelial ovarian cancer (OC) present ascites at diagnosis and almost all have ascites at recurrence especially because of the propensity of the OC cells to spread in the abdominal cavity leading to peritoneal metastasis. The influence of ascites on the development of pre-metastatic niches, and on the biological mechanisms leading to cancer cell colonization of the mesothelium, remains poorly understood. Here, we show that ascites weakens the mesothelium by affecting the morphology of mesothelial cells and by destabilizing their distribution in the cell cycle. Ascites also causes destabilization of the integrity of mesothelium by modifying the organization of cell junctions, but it does not affect the synthesis of N-cadherin and ZO-1 by mesothelial cells. Moreover, ascites induces disorganization of focal contacts and causes actin cytoskeletal reorganization potentially dependent on the activity of Rac1. Ascites allows the densification and reorganization of ECM proteins of the mesothelium, especially fibrinogen/fibrin, and indicates that it is a source of the fibrinogen and fibrin surrounding OC spheroids. The fibrin in ascites leads to the adhesion of OC spheroids to the mesothelium, and ascites promotes their disaggregation followed by the clearance of mesothelial cells. Both αV and α5ß1 integrins are involved. In conclusion ascites and its fibrinogen/fibrin composition affects the integrity of the mesothelium and promotes the integrin-dependent implantation of OC spheroids in the mesothelium.
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Ascitis , Fibrina , Fibrinógeno , Integrina alfa5beta1 , Neoplasias Ováricas , Esferoides Celulares , Microambiente Tumoral , Humanos , Femenino , Neoplasias Ováricas/patología , Neoplasias Ováricas/metabolismo , Ascitis/patología , Ascitis/metabolismo , Integrina alfa5beta1/metabolismo , Esferoides Celulares/metabolismo , Esferoides Celulares/patología , Fibrinógeno/metabolismo , Fibrina/metabolismo , Neoplasias Peritoneales/secundario , Neoplasias Peritoneales/metabolismo , Neoplasias Peritoneales/patología , Carcinoma Epitelial de Ovario/metabolismo , Carcinoma Epitelial de Ovario/patología , Línea Celular Tumoral , Receptores de Vitronectina/metabolismo , Proteína de Unión al GTP rac1/metabolismo , Adhesión Celular , Peritoneo/patología , Peritoneo/metabolismo , Epitelio/metabolismo , Epitelio/patología , Cadherinas/metabolismo , Células Tumorales CultivadasRESUMEN
Objective: The prognosis of malignant tumors with peritoneal metastases and cancerous ascites has generally been poor, with limited treatment options. The PRaG regimen, which comprised of hypofractionated radiotherapy, programmed cell death-1 (PD-1) inhibitor, and granulocyte-macrophage colony-stimulating factor (GM-CSF), showed a survival advantage in patients with advanced solid tumors who failed at least the first line of standard systemic treatment. Intraperitoneal infusion of PD-1 inhibitors may be a novel therapeutic strategy for managing malignant ascites. Integrating the PRaG regimen with intraperitoneal perfusion of a PD-1 inhibitor might control malignant ascites and provide further survival benefits in these patients. This proposed study aims to investigate the safety and efficacy of intraperitoneal infusion of serplulimab in combination with the PRaG regimen in patients with simultaneous advanced solid tumors and cancerous ascites who fail at least the first-line treatment. Methods: This proposed study is a prospective, single-arm, open-label, multicenter clinical trial. All eligible patients will receive 2 cycles of intensive treatment, a combination of PRaG regimen with an intraperitoneal infusion of PD-1 inhibitor. The patients who are beneficially treated with intensive treatment will receive consolidation treatment every 2 weeks until ascites disappear, disease progression occurs, intolerable toxicity occurs, or for up to 1 year. Phase I of this study will be conducted using a modified 3 + 3 design. The dose of intraperitoneal infusion of PD-1 inhibitor for phase II will be determined according to dose-limiting toxicity evaluation in the phase I study. Conclusion: This prospective, open-label, multicenter study will potentially lead to intraperitoneal perfusion of a PD-1 inhibitor being a new strategy for malignant ascites patients and provide a meaningful efficacy and safety of the combination of PRaG regimen with an intraperitoneal infusion of PD-1 inhibitor for these patients.
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Ascitis , Inhibidores de Puntos de Control Inmunológico , Infusiones Parenterales , Neoplasias , Humanos , Ascitis/etiología , Ascitis/tratamiento farmacológico , Ascitis/patología , Femenino , Masculino , Persona de Mediana Edad , Neoplasias/tratamiento farmacológico , Neoplasias/complicaciones , Neoplasias/patología , Inhibidores de Puntos de Control Inmunológico/administración & dosificación , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Adulto , Anciano , Neoplasias Peritoneales/tratamiento farmacológico , Neoplasias Peritoneales/secundario , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Resultado del Tratamiento , Estudios ProspectivosRESUMEN
Albumin infusions improve circulatory and renal function in patients with decompensated cirrhosis. However, there is no convincing evidence that hypoalbuminemia contributes to ascites formation in liver cirrhosis. The aim of our study is to determine the exact role of hypoalbuminemia in the formation of ascites caused by liver cirrhosis and its underlying mechanism. Clinical profiles of patients with liver cirrhosis retrospectively analyzed. The details of albumin involved in ascites formation were investigated in rat model and murine model. Statistical analysis demonstrated hypoalbuminemia was an independent risk factor for ascites formation in patients with liver cirrhosis (OR = 0.722, P < 0.001). In carbon tetrachloride (CCl4)-induced rat model of liver cirrhosis, a significant reduction in serum albumin was observed in rats with ascites (13.37 g/L) compared with rats without ascites (21.43 g/L, P < 0.001). In thioacetamide (TAA)-treated mice, ascites amount of heterozygous albumin (Alb+/-) mice (112.0 mg) was larger than that of wild-type (Alb+/+) mice (58.46 mg, P < 0.001). In CCl4-induced chronic liver injury, ascites amounts of Alb+/- or Alb+/+ mice were 80.00 mg or 48.46 mg (P = 0.001). Further study demonstrated 24-h urinary sodium excretion in Alb+/- mice was lower than that of Alb+/+ mice in TAA/CCl4-induce murine models of liver cirrhosis. Additionally, serum sodium concentration of Alb+/- mice was lower than that of Alb+/+ mice. In cirrhotic mice, higher level of antidiuretic hormone was observed in Alb+/- mice compared with the control; and renal aquaporin (AQP2) expression in Alb+/- mice was significantly higher than that of WT mice. These revealed hypoalbuminemia contributed to the occurrence of ascites in liver cirrhosis through sodium and water retention.
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Ascitis , Hipoalbuminemia , Cirrosis Hepática , Sodio , Animales , Hipoalbuminemia/metabolismo , Hipoalbuminemia/patología , Ascitis/metabolismo , Ascitis/patología , Sodio/metabolismo , Sodio/orina , Ratones , Masculino , Humanos , Cirrosis Hepática/metabolismo , Cirrosis Hepática/patología , Cirrosis Hepática/complicaciones , Cirrosis Hepática/genética , Femenino , Ratas , Tetracloruro de Carbono/toxicidad , Tetracloruro de Carbono/efectos adversos , Persona de Mediana Edad , Acuaporina 2/metabolismo , Acuaporina 2/genética , Modelos Animales de Enfermedad , Estudios Retrospectivos , Albúmina Sérica/metabolismo , Tioacetamida , Agua/metabolismo , AncianoRESUMEN
Platinum-resistant high-grade serous carcinoma (HGSC) is an incurable disease, so biomarkers that could help with timely treatment adjustments and personalized approach are extensively being sought. Tumor-derived extracellular vesicles (EVs) that can be isolated from ascites and blood of HGSC patients are such promising biomarkers. Epithelial cell adhesion molecule (EpCAM) expression is upregulated in most epithelium-derived tumors; however, studies on prognostic value of EpCAM overexpression in ovarian carcinoma have shown contradictory results. The aim of our study was to evaluate the potential of total and EpCAM-positive EVs as prognostic and predictive biomarkers for advanced HGSC. Flow cytometry was used to determine the concentration of total and EpCAM-positive EVs in paired pretreatment ascites and plasma samples of 37 patients with advanced HGSC who underwent different first-line therapy. We found that higher EpCAM-positive EVs concentration in ascites is associated with shorter progression-free survival (PFS) regardless of treatment strategy. We also found a strong correlation of EpCAM-positive EVs concentration between ascites and plasma. Our findings indicate that EpCAM-positive EVs in ascites of patients with advanced HGSC have the potential to serve as prognostic biomarkers for predicting early recurrence and thereby likelihood of more aggressive tumor biology and development of chemoresistance.
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Ascitis , Biomarcadores de Tumor , Cistadenocarcinoma Seroso , Molécula de Adhesión Celular Epitelial , Vesículas Extracelulares , Neoplasias Ováricas , Supervivencia sin Progresión , Humanos , Molécula de Adhesión Celular Epitelial/metabolismo , Vesículas Extracelulares/metabolismo , Femenino , Ascitis/metabolismo , Ascitis/patología , Persona de Mediana Edad , Anciano , Biomarcadores de Tumor/metabolismo , Cistadenocarcinoma Seroso/metabolismo , Cistadenocarcinoma Seroso/patología , Cistadenocarcinoma Seroso/mortalidad , Neoplasias Ováricas/metabolismo , Neoplasias Ováricas/patología , Neoplasias Ováricas/mortalidad , Pronóstico , Adulto , Clasificación del TumorRESUMEN
BACKGROUND: Peritoneal carcinomatosis was the main reason leading to gastric cancer (GC)-related death. We aimed to explore the roles of dysregulated microRNAs (miRNAs) and related immune regulation activities in GC-associated malignant ascites. METHODS: GSE126399 were downloaded from GEO database. Differentially expressed miRNAs in GC ascites samples was firstly screened, and critical miRNAs were further investigated by LASSO (least absolute shrinkage and selection operator) logistic regression and random forest (RF) algorithm. Receiver operating characteristic of critical miRNAs was also constructed. Moreover, functional analysis, immune cell infiltration associated with differentially expressed mRNAs were further analyzed. After selecting key modules by weighted gene co-expression network analysis, mRNAs related with survival performance and transcription factor (TF)-miRNA-mRNA network were constructed. RESULTS: Hsa-miR-181b-5p was confirmed as critical differentially expressed miRNAs in GC ascites. Then, the tumor samples were divided into high- and low- expression groups divided by mean expression levels of hsa-miR-181b-5p, and subjects with high hsa-miR-181b-5p levels had better survival outcomes. In total, 197 differentially expressed mRNAs associated with hsa-miR-181b-5p levels were obtained, and these mRNAs were mainly enriched in muscle activity and vascular smooth muscle contraction. Hsa-miR-181b-5 was positively related with activated CD4 T cells and negatively related with eosinophil. 17 mRNAs were selected as mRNAs significantly related with prognosis of GC, such as PDK4 and RAMP1. Finally, 75 TF-miRNA-mRNA relationships were obtained, including 15 TFs, hsa-miR-181b-5p, and five mRNAs. CONCLUSION: Our data suggest that the differentially expressed hsa-miR-181b-5p in ascites samples of GC patients may be a valuable prognostic marker and a potential target for therapeutic intervention, which should be validated in the near future.
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Ascitis , Biomarcadores de Tumor , MicroARNs , Neoplasias Gástricas , Humanos , MicroARNs/genética , MicroARNs/metabolismo , Neoplasias Gástricas/genética , Neoplasias Gástricas/patología , Ascitis/genética , Ascitis/metabolismo , Ascitis/patología , Pronóstico , Biomarcadores de Tumor/genética , Perfilación de la Expresión Génica , Redes Reguladoras de Genes , Regulación Neoplásica de la Expresión Génica , ARN Mensajero/genética , ARN Mensajero/metabolismoRESUMEN
Acute pancreatitis (AP) is an acute inflammatory reaction of the pancreatic tissue, which involves auto-digestion, edema, hemorrhage, and necrosis. AP can be categorized into mild, moderately severe, and severe AP, with severe pancreatitis also referred to as acute necrotizing pancreatitis (ANP). ANP is characterized by the accumulation of necrotic material in the peritoneal cavity. This can result in intestinal injury. However, the mechanism of ANP-associated intestinal injury remains unclear. We established an ANP-associated intestinal injury rat model (ANP-IR model) by injecting pancreatitis-associated ascites fluid (PAAF) and necrotic pancreatic tissue at various proportions into the triangular area formed by the left renal artery and ureter. The feasibility of the ANP-IR model was verified by comparing the similar changes in indicators of intestinal inflammation and barrier function between the two rat models. In addition, we detected changes in apoptosis levels and YAP protein expression in the ileal tissues of rats in each group and validated them in vitro in rat epithelial crypt cells (IEC-6) to further explore the potential injury mechanisms of ANP-associated intestinal injury. We also collected clinical data from patients with ANP to validate the effects of PAAF and pancreatic necrosis on intestinal injury. Our findings offer a theoretical basis for restricting the buildup of peritoneal necrosis in individuals with ANP, thus promoting the restoration of intestinal function and enhancing treatment efficacy. The use of the ANP-IR model in further studies can help us better understand the mechanism and treatment of ANP-associated intestinal injury.NEW & NOTEWORTHY We constructed a rat model of acute necrotizing pancreatitis-associated intestinal injury and verified its feasibility. In addition, we identified the mechanism by which necrotic pancreatic tissue and pancreatitis-associated ascites fluid (PAAF) cause intestinal injury through the HIPPO signaling pathway.
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Apoptosis , Modelos Animales de Enfermedad , Pancreatitis Aguda Necrotizante , Ratas Sprague-Dawley , Proteínas Señalizadoras YAP , Animales , Pancreatitis Aguda Necrotizante/patología , Pancreatitis Aguda Necrotizante/metabolismo , Pancreatitis Aguda Necrotizante/complicaciones , Ratas , Masculino , Proteínas Señalizadoras YAP/metabolismo , Humanos , Páncreas/patología , Páncreas/metabolismo , Ascitis/metabolismo , Ascitis/patología , Línea Celular , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologíaRESUMEN
Immune exhaustion is a hallmark of ovarian cancer. Using multiparametric flow cytometry, the study aimed to analyze protein expression of novel immunological targets on CD3+ T cells isolated from the peripheral blood (n = 20), malignant ascites (n = 16), and tumor tissue (n = 6) of patients with ovarian cancer (OVCA). The study revealed an increased proportion of effector memory CD8+ T cells in OVCA tissue and malignant ascites. An OVCA-characteristic PD-1high CD8+ T cell population was detected, which differed from PD-1lowCD8+ T cells by increased co-expression of TIGIT, CD39, and HLA-DR. In addition, these OVCA-characteristic CD8+ T cells showed reduced expression of the transcription factor TCF-1, which may also indicate reduced effector function and memory formation. On the contrary, the transcription factor TOX, which significantly regulates terminal T cell-exhaustion, was found more frequently in these cells. Further protein and gene analysis showed that CD39 and CD73 were also expressed on OVCA tumor cells isolated from solid tumors (n = 14) and malignant ascites (n = 9). In the latter compartment, CD39 and CD73 were also associated with the expression of the "don't eat me" molecule CD24 on tumor cells. Additionally, ascites-derived CD24+EpCAM+ tumor cells showed a higher frequency of CD39+ or CD73+ cells. Furthermore, CD39 expression was associated with unfavorable clinical parameters. Expression of CD39 on T cells was upregulated through CD3/CD28 stimulation and its blockade by a newly developed nanobody construct resulted in increased proliferation (eFluor), activation (CD25 and CD134), and production of cytotoxic cytokines (IFN-γ, TNF-α, and granzyme-B) of CD8+ T cells.
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Apirasa , Linfocitos T CD8-positivos , Neoplasias Ováricas , Humanos , Femenino , Neoplasias Ováricas/inmunología , Neoplasias Ováricas/patología , Neoplasias Ováricas/metabolismo , Apirasa/metabolismo , Apirasa/genética , Linfocitos T CD8-positivos/inmunología , Linfocitos T CD8-positivos/metabolismo , Persona de Mediana Edad , Ascitis/inmunología , Ascitis/patología , Ascitis/metabolismo , Antígenos CD/metabolismo , Antígenos CD/genética , Anciano , Receptor de Muerte Celular Programada 1/metabolismo , Receptores Inmunológicos/metabolismo , Receptores Inmunológicos/genética , Receptores Inmunológicos/antagonistas & inhibidores , Factor 1 de Transcripción de Linfocitos T/metabolismo , Factor 1 de Transcripción de Linfocitos T/genética , Antígenos HLA-DR/metabolismo , Adulto , Agotamiento de Células T , Proteínas del Grupo de Alta MovilidadAsunto(s)
Ascitis , Neoplasias Encefálicas , Glioma , Inhibidores de Proteínas Quinasas , Proteínas Proto-Oncogénicas B-raf , Derivación Ventriculoperitoneal , Humanos , Proteínas Proto-Oncogénicas B-raf/antagonistas & inhibidores , Proteínas Proto-Oncogénicas B-raf/genética , Glioma/tratamiento farmacológico , Glioma/patología , Niño , Ascitis/etiología , Ascitis/tratamiento farmacológico , Ascitis/patología , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/patología , Inhibidores de Proteínas Quinasas/uso terapéutico , Inhibidores de Proteínas Quinasas/efectos adversos , Masculino , Femenino , Preescolar , Adolescente , Piridonas , PirimidinonasAsunto(s)
Ascitis , Factor Estimulante de Colonias de Granulocitos , Neoplasias Ováricas , Femenino , Humanos , Persona de Mediana Edad , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Ascitis/etiología , Ascitis/patología , Granulocitos , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/patologíaRESUMEN
Detection of peritoneal dissemination (PD) in gastric cancer (GC) patients remains challenging. The feasibility of tumor-guided cell-free DNA (cfDNA) detection in prospectively collected peritoneal fluid (ascites and peritoneal lavage) was investigated and compared to conventional cytology in 28 patients. Besides conventional cytology, next generation sequencing was performed on primary tumor DNA and cell-free DNA from peritoneal fluid. Patients were retrospectively grouped into: a positive group (with PD) and a negative group (without PD). Detectable mutations were found in the primary tumor of 68% (n = 19). Sensitivity of PD detection by tumor-guided cfDNA analysis was 91%, compared to 64% by conventional cytology. Within the positive group (n = 11), tumor-guided cfDNA was detected in all patients with ascites samples (4/4, 100%) and in 86% (6/7) of the lavage samples, opposed to 4/4 (100%) patients with ascites and 43% (3/7) with lavage by conventional cytology. Within the negative group (n = 8), conventional cytology was negative for all samples. In two patients, tumor-guided cfDNA was detected in peritoneal lavage fluid. Interestingly, these 2 patients developed PD within 6 months, suggesting a prognostic value of tumor-guided cfDNA detection. This study showed that tumor-guided cfDNA detection in peritoneal fluids of GC patients is feasible and superior to conventional cytology in detecting PD.
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Líquido Ascítico , Ácidos Nucleicos Libres de Células , Neoplasias Peritoneales , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/genética , Neoplasias Gástricas/patología , Neoplasias Gástricas/diagnóstico , Neoplasias Peritoneales/secundario , Neoplasias Peritoneales/genética , Neoplasias Peritoneales/diagnóstico , Femenino , Líquido Ascítico/patología , Líquido Ascítico/metabolismo , Masculino , Persona de Mediana Edad , Anciano , Ácidos Nucleicos Libres de Células/genética , Estudios Retrospectivos , ADN Tumoral Circulante/genética , Adulto , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Biomarcadores de Tumor/genética , Ascitis/genética , Ascitis/patología , Ascitis/diagnóstico , Mutación , Anciano de 80 o más Años , Lavado Peritoneal , ADN de Neoplasias/genética , ADN de Neoplasias/análisisRESUMEN
Cancer of unknown primary (CUP) site poses diagnostic challenges due to its elusive nature. Many cases of CUP manifest as pleural and peritoneal serous effusions. Leveraging cytological images from 57,220 cases at four tertiary hospitals, we developed a deep-learning method for tumor origin differentiation using cytological histology (TORCH) that can identify malignancy and predict tumor origin in both hydrothorax and ascites. We examined its performance on three internal (n = 12,799) and two external (n = 14,538) testing sets. In both internal and external testing sets, TORCH achieved area under the receiver operating curve values ranging from 0.953 to 0.991 for cancer diagnosis and 0.953 to 0.979 for tumor origin localization. TORCH accurately predicted primary tumor origins, with a top-1 accuracy of 82.6% and top-3 accuracy of 98.9%. Compared with results derived from pathologists, TORCH showed better prediction efficacy (1.677 versus 1.265, P < 0.001), enhancing junior pathologists' diagnostic scores significantly (1.326 versus 1.101, P < 0.001). Patients with CUP whose initial treatment protocol was concordant with TORCH-predicted origins had better overall survival than those who were administrated discordant treatment (27 versus 17 months, P = 0.006). Our study underscores the potential of TORCH as a valuable ancillary tool in clinical practice, although further validation in randomized trials is warranted.
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Aprendizaje Profundo , Neoplasias Primarias Desconocidas , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Ascitis/patología , Citodiagnóstico/métodos , Neoplasias Primarias Desconocidas/patología , Curva ROCRESUMEN
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.
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Cistadenocarcinoma Seroso , Vesículas Extracelulares , Neoplasias Ováricas , Humanos , Femenino , Ascitis/metabolismo , Ascitis/patología , Microambiente Tumoral , Proteómica , Cistadenocarcinoma Seroso/diagnóstico , Cistadenocarcinoma Seroso/genética , Cistadenocarcinoma Seroso/metabolismo , Vesículas Extracelulares/metabolismo , Neoplasias Ováricas/diagnósticoRESUMEN
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.
Asunto(s)
Infecciones por Virus de Epstein-Barr , Linfoma Extranodal de Células NK-T , Linfoma de Células T Periférico , Masculino , Humanos , Persona de Mediana Edad , Infecciones por Virus de Epstein-Barr/complicaciones , Herpesvirus Humano 4 , Linfoma de Células T Periférico/complicaciones , Linfoma de Células T Periférico/diagnóstico , Linfoma de Células T Periférico/tratamiento farmacológico , Prednisona , Linfoma Extranodal de Células NK-T/complicaciones , Linfoma Extranodal de Células NK-T/diagnóstico , Ascitis/complicaciones , Ascitis/patología , Células Asesinas Naturales/patología , ADNAsunto(s)
Ascitis , Inmunoglobulina M , Paraproteinemias , Policitemia , Telangiectasia , Anciano , Humanos , Persona de Mediana Edad , Ascitis/etiología , Ascitis/diagnóstico , Ascitis/patología , Inmunoglobulina M/sangre , Paraproteinemias/diagnóstico , Paraproteinemias/complicaciones , Policitemia/diagnóstico , Policitemia/etiología , Policitemia/complicaciones , Síndrome , Telangiectasia/diagnóstico , Telangiectasia/etiología , Telangiectasia/patologíaRESUMEN
BACKGROUND: Cancer, a predominant cause of mortality, poses a formidable challenge in our pursuit of elevating life expectancy. Throughout history, individuals have sought natural remedies with minimal side effects as an appealing substitute for chemotherapeutic drugs. One such remedy is Cordyceps militaris, a renowned medicinal mushroom deeply entrenched in Asian ethnomedicine. Revered for its rejuvenating and curative attributes, it relied upon for ages. OBJECTIVE: The mushroom's soaring demand outpaced natural availability, necessitating controlled laboratory cultivation as the core focus and exploring the potential of methanolic extracts from harvested Cordyceps militaris fruiting bodies against Dalton's Lymphoma Ascites (DLA) cells in vitro, with a specific emphasis on its anticancer traits. METHODS: For cultivation, we employed a diverse range of rice substrates, among which bora rice showed promising growth of C. militaris fruiting bodies. To assess DLA cell cytotoxicity, several assays, including trypan blue exclusion assay, MTT assay, and LDH assay, were employed at different time points (24-96 h), which provided valuable insights on DLA cell viability and proliferation, shedding light on its therapeutic potential against cancer. RESULTS: Our studies unveiled that methanolic extract prompts apoptosis in DLA cells via AO/EB dual staining, manifesting consistent apoptosis indicators such as membrane blebbing, chromatin condensation, nuclei fragmentation, and cellular shrinkage at 48-96 h of treatment. Furthermore, these striking repercussions of apoptosis were comprehended by an in silico approach having molecular docking simulation against antiapoptotic proteins like BCL-2, BCL-XL, MCL-1, BFL-1 & HSP100. CONCLUSION: Methanolic C. militaris extracts exhibited cytotoxicity and apoptotic alterations in DLA cells.
Asunto(s)
Antineoplásicos , Apoptosis , Proliferación Celular , Cordyceps , Ensayos de Selección de Medicamentos Antitumorales , Linfoma , Cordyceps/química , Antineoplásicos/farmacología , Antineoplásicos/química , Antineoplásicos/aislamiento & purificación , Proliferación Celular/efectos de los fármacos , Apoptosis/efectos de los fármacos , Linfoma/tratamiento farmacológico , Linfoma/patología , Relación Dosis-Respuesta a Droga , Animales , Humanos , Relación Estructura-Actividad , Ascitis/patología , Ascitis/tratamiento farmacológico , Células Tumorales Cultivadas , Supervivencia Celular/efectos de los fármacos , Estructura Molecular , Ratones , Línea Celular Tumoral , Simulación del Acoplamiento MolecularRESUMEN
Late cardiotoxicity is a formidable challenge in anthracycline-based anticancer treatments. Previous research hypothesized that co-administration of carvedilol (CVD) and dexrazoxane (DEX) might provide superior protection against doxorubicin (DOX)-induced cardiotoxicity compared to DEX alone. However, the anticipated benefits were not substantiated by the findings. This study focuses on investigating the impact of CVD on myocardial redox system parameters in rats treated with DOX + DEX, examining its influence on overall toxicity and iron metabolism. Additionally, considering the previously observed DOX-induced ascites, a seldom-discussed condition, the study explores the potential involvement of the liver in ascites development. Compounds were administered weekly for ten weeks, with a specific emphasis on comparing parameter changes between DOX + DEX + CVD and DOX + DEX groups. Evaluation included alterations in body weight, feed and water consumption, and analysis of NADPH2, NADP+, NADPH2/NADP+, lipid peroxidation, oxidized DNA, and mRNA for superoxide dismutase 2 and catalase expressions in cardiac muscle. The iron management panel included markers for iron, transferrin, and ferritin. Liver abnormalities were assessed through histological examinations, aspartate transaminase, alanine transaminase, and serum albumin level measurements. During weeks 11 and 21, reduced NADPH2 levels were observed in almost all examined groups. Co-administration of DEX and CVD negatively affected transferrin levels in DOX-treated rats but did not influence body weight changes. Ascites predominantly resulted from cardiac muscle dysfunction rather than liver-related effects. The study's findings, exploring the impact of DEX and CVD on DOX-induced cardiotoxicity, indicate a lack of scientific justification for advocating the combined use of these drugs at histological, biochemical, and molecular levels.
Asunto(s)
Ascitis , Cardiotoxicidad , Ratas , Animales , Carvedilol/farmacología , NADP/metabolismo , Cardiotoxicidad/metabolismo , Ascitis/patología , Doxorrubicina/uso terapéutico , Miocardio/metabolismo , Antibióticos Antineoplásicos/uso terapéutico , Hierro/metabolismo , Peroxidación de Lípido , Hígado/metabolismo , Transferrina/metabolismo , Peso CorporalRESUMEN
BACKGROUND: No data on the use of 2D shear wave elastography exists regarding the evaluation of the new-onset ascites causality. AIMS: To determine whether 2D shear wave elastography can help in the non-invasive assessment of the new-onset ascites cause. To assess the applicability of liver stiffness measured by 2D shear wave elastography using Esaote MyLab Nine apparatus in patients with ascites. METHODS: In 52 consecutive patients with new-onset ascites (January 2020 to October 2021), liver stiffness using 2D shear wave elastography was prospectively measured. The reliable measurements were used for further analysis. Relevant clinical and laboratory data was collected. RESULTS: The calculated liver stiffness measurement cut-off value of 14.4 kPa held 94% accuracy, 100% sensitivity, and 83% specificity when determining ascites with serum ascites albumin gradient ≥11 g/L. Reliable 2D shear wave elastography success rate was 84%. CONCLUSIONS: 2D shear wave elastography may potentially be used to differentiate transudative from exudative ascites, especially in patients with portal hypertension and peritoneal carcinomatosis.