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1.
J Extracell Vesicles ; 13(3): e12420, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38490958

RESUMO

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.


Assuntos
Cistadenocarcinoma Seroso , Vesículas Extracelulares , Neoplasias Ovarianas , Humanos , Feminino , Ascite/metabolismo , Ascite/patologia , Microambiente Tumoral , Proteômica , Cistadenocarcinoma Seroso/diagnóstico , Cistadenocarcinoma Seroso/genética , Cistadenocarcinoma Seroso/metabolismo , Vesículas Extracelulares/metabolismo , Neoplasias Ovarianas/diagnóstico
2.
J Clin Exp Hematop ; 64(1): 52-58, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38538319

RESUMO

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.


Assuntos
Infecções por Vírus Epstein-Barr , Linfoma Extranodal de Células T-NK , Linfoma de Células T Periférico , Masculino , Humanos , Pessoa de Meia-Idade , Infecções por Vírus Epstein-Barr/complicações , Herpesvirus Humano 4 , Linfoma de Células T Periférico/complicações , Linfoma de Células T Periférico/diagnóstico , Linfoma de Células T Periférico/tratamento farmacológico , Prednisona , Linfoma Extranodal de Células T-NK/complicações , Linfoma Extranodal de Células T-NK/diagnóstico , Ascite/complicações , Ascite/patologia , Células Matadoras Naturais/patologia , DNA
3.
ACS Nano ; 18(8): 6130-6146, 2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38349890

RESUMO

Gastric cancer is one of the most prevalent digestive malignancies. The lack of effective in vitro peritoneal models has hindered the exploration of the potential mechanisms behind gastric cancer's peritoneal metastasis. An accumulating body of research indicates that small extracellular vesicles (sEVs) play an indispensable role in peritoneal metastasis of gastric cancer cells. In this study, a biomimetic peritoneum was constructed. The biomimetic model is similar to real peritoneum in internal microstructure, composition, and primary function, and it enables the recurrence of peritoneal metastasis process in vitro. Based on this model, the association between the mechanical properties of sEVs and the invasiveness of gastric cancer was identified. By performing nanomechanical analysis on sEVs, we found that the Young's modulus of sEVs can be utilized to differentiate between malignant clinical samples (ascites) and nonmalignant clinical samples (peritoneal lavage). Furthermore, patients' ascites-derived sEVs were verified to stimulate the mesothelial-to-mesenchymal transition, thereby promoting peritoneal metastasis. In summary, nanomechanical analysis of living sEVs could be utilized for the noninvasive diagnosis of malignant degree and peritoneal metastasis of gastric cancer. This finding is expected to contribute future treatments.


Assuntos
Vesículas Extracelulares , Neoplasias Peritoneais , Neoplasias Gástricas , Humanos , Peritônio/patologia , Neoplasias Gástricas/diagnóstico , Neoplasias Peritoneais/diagnóstico , Ascite/patologia , Biomimética , Vesículas Extracelulares/patologia
4.
Anticancer Res ; 44(2): 613-619, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38307557

RESUMO

BACKGROUND/AIM: Cell-free and concentrated ascites reinfusion therapy (CART) was established for refractory ascites and renovated CART (Keisuke Matsusaki (KM) -CART) has been recently developed especially for malignant ascites; however, the actual clinical efficacy of KM-CART has been rarely reported. PATIENTS AND METHODS: We performed 226 KM-CART procedures in 104 patients with malignant ascites in three hospitals from August 2013 to September 2018. Medical records were retrospectively reviewed for ascites data, related complications, symptoms before and after each CART and prognosis after the first CART. The modified Glasgow Prognostic Score (mGPS) was reviewed before every procedure, as an indicator of nutritional status. RESULTS: Pancreatic cancer was the most common indication for the KM-CART procedure, followed by gastric cancer, hepatocellular carcinoma, ovarian cancer, and cholangiocarcinoma (five major diseases). The 50% survival times of these five major diseases after the first procedure were 25, 39, 31, 49, and 33 days, respectively. The mean survival time for all patients was 73.5 days, and 75.6 days for those with the five major diseases. All patients experienced symptomatic relief, and complications were rare. Repeated KM-CART was performed in 47.1% of the patients, most often in those with ovarian cancer (66.7%). Regarding the mGPS at the first CART procedure, 89% of patients were in the group with the poorest nutritional status. Patients who underwent KM-CART three or more times had longer survival than those who were treated once or twice. CONCLUSION: Repeated KM-CART provides a survival benefit for patients with malignant ascites, even in cases of poor nutritional status.


Assuntos
Neoplasias dos Ductos Biliares , Neoplasias Hepáticas , Neoplasias Ovarianas , Neoplasias Peritoneais , Feminino , Humanos , Ascite/etiologia , Ascite/terapia , Ascite/patologia , Estudos Retrospectivos , Neoplasias Peritoneais/complicações , Neoplasias Ovarianas/complicações , Neoplasias Hepáticas/complicações , Neoplasias dos Ductos Biliares/complicações , Ductos Biliares Intra-Hepáticos/patologia
5.
BMC Gastroenterol ; 24(1): 68, 2024 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-38331713

RESUMO

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.


Assuntos
Técnicas de Imagem por Elasticidade , Hipertensão Portal , Humanos , Cirrose Hepática/complicações , Cirrose Hepática/diagnóstico por imagem , Cirrose Hepática/patologia , Ascite/diagnóstico por imagem , Ascite/etiologia , Ascite/patologia , Fígado/patologia , Hipertensão Portal/patologia
6.
Int J Mol Sci ; 25(4)2024 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-38396896

RESUMO

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.


Assuntos
Ascite , Cardiotoxicidade , Ratos , Animais , Carvedilol/farmacologia , NADP/metabolismo , Cardiotoxicidade/metabolismo , Ascite/patologia , Doxorrubicina/uso terapêutico , Miocárdio/metabolismo , Antibióticos Antineoplásicos/uso terapêutico , Ferro/metabolismo , Peroxidação de Lipídeos , Fígado/metabolismo , Transferrina/metabolismo , Peso Corporal
7.
Cell Rep ; 43(1): 113613, 2024 01 23.
Artigo em Inglês | MEDLINE | ID: mdl-38232734

RESUMO

Malignant ascites accompanied by peritoneal dissemination contain various factors and cell populations as well as cancer cells; however, how the tumor microenvironment is shaped in ascites remains unclear. Single-cell proteomic profiling and a comprehensive proteomic analysis are conducted to comprehensively characterize malignant ascites. Here, we find defects in immune effectors along with immunosuppressive cell accumulation in ascites of patients with gastric cancer (GC) and identify five distinct subpopulations of CD45(-)/EpCAM(-) cells. Mesothelial cells with mesenchymal features in CD45(-)/EpCAM(-) cells are the predominant source of chemokines involved in immunosuppressive myeloid cell (IMC) recruitment. Moreover, mesothelial-mesenchymal transition (MMT)-induced mesothelial cells strongly express extracellular matrix (ECM)-related genes, including tenascin-C (TNC), enhancing metastatic colonization. These findings highlight the definite roles of the mesenchymal cell population in the development of a protumorigenic microenvironment to promote peritoneal dissemination.


Assuntos
Ascite , Neoplasias Peritoneais , Humanos , Ascite/patologia , Molécula de Adesão da Célula Epitelial , Proteômica , Peritônio/patologia , Neoplasias Peritoneais/patologia , Linhagem Celular Tumoral , Microambiente Tumoral
8.
Clin Exp Med ; 24(1): 25, 2024 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-38281236

RESUMO

Ascites is the most common complication of liver cirrhosis. Spontaneous bacterial peritonitis (SBP) is a common complication of ascites. The diagnosis is made by an ascitic fluid polymorphonuclear (PMN) cell count of ≥ 250/mm3. However, no other diagnostic test is present for the diagnosis of SBP. The aim of the study present study is to assess the diagnostic yield of ascitic calprotectin in SBP, and to explore whether it can predict disease stage. We performed a single center proof-of-concept prospective study including all patients with cirrhosis and ascites who underwent paracentesis. Overall, 31 patients were included in the study. Eight patients had SBP vs. 23 patients without SBP. Ascitic calprotectin level was 77.4 ± 86.5 µg/mL in the SBP group, as compared to 16.1 ± 5.6 µg/mL in the non-SBP group (P = 0.001). An ascitic calprotectin cut-off value of > 21 µg/mL was associated with sensitivity and specificity of 85.7% and 89.5%, respectively, with ROC of 0.947 (95% CI 0.783 to 0.997, P < 0.0001). Notably, ascitic calprotectin did not had a prognostic value in cirrhosis stage and prognosis. Ascitic calprotectin was highly accurate in the diagnosis of SBP. It can be a serve as adjunct for indefinite cases of SBP.


Assuntos
Infecções Bacterianas , Peritonite , Humanos , Líquido Ascítico/microbiologia , Líquido Ascítico/patologia , Ascite/diagnóstico , Ascite/complicações , Ascite/patologia , Estudos Prospectivos , Complexo Antígeno L1 Leucocitário , Infecções Bacterianas/etiologia , Infecções Bacterianas/microbiologia , Cirrose Hepática/complicações , Cirrose Hepática/diagnóstico , Peritonite/etiologia , Peritonite/microbiologia
9.
Mol Oncol ; 18(1): 136-155, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38010623

RESUMO

High-grade serous ovarian cancer (HGSOC) is the deadliest gynecological malignancy. The most common form of metastatic spread of HGSOC is transcoelomic dissemination. In this process, detached cells from the primary tumor aggregate as tumorspheres and promote the accumulation of peritoneal ascites. This represents an early event in HGSOC development and is indicative of poor prognosis. In this study, based on tumorspheres isolated from ascitic liquid samples from HGSOC patients, ovarian cancer spheroid 3D cultures, and in vivo models, we describe a key signal for tumorsphere formation in HGSOC. We report that platelet-derived growth factor receptor beta (PDGFRß) is essential for fibronectin-mediated cell clustering of ovarian cancer cells into tumorspheres. This effect is mediated by the kinase NUAK family SNF1-like kinase 1 (NUAK1) and blocked by PDGFRß pharmacological or genetic inhibition. In the absence of PDGFRß, ovarian cancer cells can be provided with fibronectin by cancer-associated fibroblasts to generate chimeric spheroids. This work provides new insights that uncover potential targets to prevent peritoneal dissemination, the main cause of advanced disease in HGSOC patients.


Assuntos
Fibroblastos Associados a Câncer , Neoplasias Ovarianas , Humanos , Feminino , Fibronectinas , Neoplasias Ovarianas/patologia , Ascite/patologia , Líquido Ascítico/metabolismo , Fibroblastos Associados a Câncer/metabolismo , Proteínas Quinases , Proteínas Repressoras
10.
Br J Nutr ; 131(2): 276-285, 2024 01 28.
Artigo em Inglês | MEDLINE | ID: mdl-37642137

RESUMO

The benefits of branched-chain amino acid (BCAA) administration after hepatic intervention in patients with liver diseases remain unclear. We conducted a systematic review and meta-analysis to evaluate the effects of BCAA on patients undergoing hepatectomy, trans-arterial embolisation and radiofrequency ablation. Relevant randomised controlled trials (RCT) were obtained from PubMed, EMBASE and Cochrane Library databases. A meta-analysis was performed to calculate the pooled effect size by using random-effects models. The primary outcomes were survival and tumour recurrence. The secondary outcomes were hospital stay, nutrition status, biochemistry profile, complication rate of liver treatment and adverse effect of BCAA supplementation. In total, eleven RCT involving 750 patients were included. Our meta-analysis showed no significant difference in the rates of tumour recurrence and overall survival between the BCAA and control groups. However, the pooled estimate showed that BCAA supplementation in patients undergoing hepatic intervention significantly increased serum albumin (mean difference (MD): 0·11 g/dl, 95 % CI: 0·02, 0·20; 5 RCT) at 6 months and cholinesterase level (MD: 50·00 U/L, 95 % CI: 21·08, 78·92; 1 RCT) at 12 months and reduced ascites incidence (risk ratio: 0·39, 95 % CI: 0·21, 0·71; 4 RCT) at 12 months compared with the control group. Additionally, BCAA administration significantly increased body weight at 6 months and 12 months and increased arm circumference at 12 months. In conclusion, BCAA supplementation significantly improved the liver function, reduced the incidence of ascites and increased body weight and arm circumference. Thus, BCAA supplementation may beneficial for selected patients undergoing liver intervention.


Assuntos
Aminoácidos de Cadeia Ramificada , Ascite , Humanos , Ascite/induzido quimicamente , Ascite/metabolismo , Ascite/patologia , Aminoácidos de Cadeia Ramificada/uso terapêutico , Recidiva Local de Neoplasia/induzido quimicamente , Recidiva Local de Neoplasia/metabolismo , Recidiva Local de Neoplasia/patologia , Fígado/metabolismo , Suplementos Nutricionais , Peso Corporal
11.
AJR Am J Roentgenol ; 222(1): e2329640, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37530396

RESUMO

BACKGROUND. The Fontan operation palliates single-ventricle congenital heart disease but causes hepatic congestion with associated progressive hepatic fibrosis. OBJECTIVE. The purpose of this study was to evaluate associations between liver stiffness measured using ultrasound (US) shear-wave elastography (SWE) in patients with Fontan palliation and the occurrence of portal hypertension and Fontan circulatory failure during follow-up. METHODS. This retrospective study included 119 individuals 10 years old or older (median age, 19.1 years; 61 female patients, 58 male patients) with Fontan circulation who underwent liver US with 2D SWE from January 1, 2015, to January 1, 2022, and had 1 year or more of clinical follow-up (unless experiencing earlier outcome-related events). Median liver stiffness from the initial US examination was documented. Varices, ascites, splenomegaly, and thrombocytopenia (VAST) scores (range, 0-4) were determined as a marker of portal hypertension on initial US examination and 1 year or more of follow-up imaging (US, CT, or MRI). Composite clinical outcome for Fontan circulatory failure (death, mechanical circulatory support, cardiac transplant, or unexpected Fontan circulation-related hospitalization) was assessed. Analysis included the Wilcoxon rank sum test, logistic regression analysis with stepwise variable selection, and ROC analysis. RESULTS. Median initial liver stiffness was 2.22 m/s. Median initial VAST score was 0 (IQR, 0-1); median follow-up VAST score was 1 (IQR, 0-2) (p = .004). Fontan circulatory failure occurred in 37 of 119 (31%) patients (median follow-up, 3.4 years). Initial liver stiffness was higher in patients with a follow-up VAST score of 1 or greater (2.37 m/s) than in those with a follow-up VAST score of 0 (2.08 m/s) (p = .005), and initial liver stiffness was higher in patients with (2.43 m/s) than without (2.10 m/s) Fontan circulatory failure during follow-up (p < .001). Initial liver stiffness was the only significant independent predictor of Fontan circulatory failure (OR = 3.76; p < .001); age, sex, Fontan operation type, dominant ventricular morphology, and initial VAST score were not independent predictors. Initial liver stiffness had an AUC of 0.70 (sensitivity, 79%; specificity, 57%; threshold, > 2.11 m/s) for predicting a follow-up VAST score of 1 or greater and an AUC of 0.74 (sensitivity, 84%; specificity, 52%; threshold, > 2.12 m/s) for predicting Fontan circulatory failure. CONCLUSION. In patients with Fontan circulation, increased initial liver stiffness was associated with portal hypertension and circulatory failure during follow-up, although it had moderate performance in predicting these outcomes. CLINICAL IMPACT. US SWE may play a role in post-Fontan surveillance, supporting tailored medical and surgical care.


Assuntos
Técnicas de Imagem por Elasticidade , Técnica de Fontan , Hipertensão Portal , Humanos , Masculino , Feminino , Adulto Jovem , Adulto , Criança , Técnicas de Imagem por Elasticidade/métodos , Estudos Retrospectivos , Ascite/patologia , Fígado/diagnóstico por imagem , Cirrose Hepática/patologia
12.
Cytopathology ; 35(1): 173-176, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37828808

RESUMO

Anorectal malignant melanomas are rare, accounting for less than 2% of all melanomas. Malignant effusions developing secondary to malignant melanoma are highly uncommon. Herein, we present the cytomorphological features of a metastatic anorectal malignant melanoma presenting with ascites at the initial clinical presentation.


Assuntos
Melanoma , Humanos , Masculino , Idoso , Melanoma/diagnóstico , Melanoma/patologia , Líquido Ascítico/patologia , Citologia , Ascite/patologia , Hemorragia Gastrointestinal/patologia
13.
Sci Adv ; 9(47): eadk1098, 2023 11 24.
Artigo em Inglês | MEDLINE | ID: mdl-38000030

RESUMO

Gastric cancer (GC) with peritoneal metastases and malignant ascites continues to have poor prognosis. Exosomes mediate intercellular communication during cancer progression and promote therapeutic resistance. Here, we report the significance of exosomes derived from malignant ascites (EXOAscites) in cancer progression and use modified exosomes as resources for cancer therapy. EXOAscites from patients with GC stimulated invasiveness and angiogenesis in an ex vivo three-dimensional autologous tumor spheroid microfluidic system. EXOAscites concentration increased invasiveness, and blockade of their secretion suppressed tumor progression. In MET-amplified GC, EXOAscites contain abundant MET; their selective delivery to tumor cells enhanced angiogenesis and invasiveness. Exosomal MET depletion substantially reduced invasiveness; an additive therapeutic effect was induced when combined with MET and/or VEGFR2 inhibition in a patient-derived MET-amplified GC model. Allogeneic MET-harboring exosome delivery induced invasion and angiogenesis in a MET non-amplified GC model. MET-amplified patient tissues showed higher exosome concentration than their adjacent normal tissues. Manipulating exosome content and production may be a promising complementary strategy against GC.


Assuntos
Exossomos , MicroRNAs , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/patologia , Ascite/patologia , Linhagem Celular Tumoral
14.
ESMO Open ; 8(6): 102048, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37977000

RESUMO

BACKGROUND: Identification of factors associated with survival after ascites diagnosis in metastatic pancreatic cancer (mPC) patients may guide treatment decisions and help to maintain quality of life in this highly symptomatic patient collective. PATIENTS AND METHODS: All patients treated for mPC at the Medical University of Vienna between 2010 and 2019 developing ascites throughout their course of disease were identified by retrospective chart review. General risk factors, metastatic sites, systemic inflammation and liver function parameters, as well as type of treatment after ascites diagnosis were investigated for associations with survival. RESULTS: One hundred and seventeen mPC patients with ascites were included in this study. Median time from mPC to ascites diagnosis was 8.9 months (range 0-99 months) and median overall survival (OS) after ascites diagnosis was 27.4 days (range 21.3-42.6 days). Identified prognostic factors at ascites diagnosis independently associated with an impaired OS were presence of liver metastases [hazard ratio (HR): 2.07, 95% confidence interval (CI) 1.13-3.79, P = 0.018), peritoneal carcinomatosis (HR: 1.74, 95% CI 1.11-2.71, P = 0.015), and portal vein obstruction (HR: 2.52, 95% CI 1.29-4.90, P = 0.007). Compared with best supportive care, continuation of systemic therapy after ascites diagnosis was independently associated with survival (HR: 0.35, 95% CI 0.20-0.61, P < 0.001) with a median OS of 62 days (95% CI 51-129 days, P < 0.001) versus 16 days (95% CI 11-24 days), respectively. CONCLUSIONS: Liver and peritoneal metastases as well as portal vein obstruction were found to be prognostic factors after ascites diagnosis in mPC patients. Continuation of systemic therapy after ascites diagnosis was associated with a longer OS, which needs to be evaluated in larger clinical trials including quality-of-life assessment.


Assuntos
Neoplasias Hepáticas , Neoplasias Pancreáticas , Humanos , Estudos Retrospectivos , Ascite/etiologia , Ascite/patologia , Qualidade de Vida , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico
15.
Cells ; 12(19)2023 09 30.
Artigo em Inglês | MEDLINE | ID: mdl-37830603

RESUMO

Tumor spheroids in the ascites of high-grade serous carcinoma (HGSC) are poorly described. Our objective was to describe their morphological features, cellular composition, PD-1 and PD-L1 expression, and survival correlation of these parameters. The density and size of spheroids were assessed in Giemsa-stained smears; the cell composition of spheroids, including tumor cells, immune cells, capillaries, and myofibroblasts, as well as PD-1 and PD-L1 expression on tumor and immune cells was assessed in immunocytochemically stained cell block sections. Forty-seven patients with primary HGSC and malignant ascites were included. A cut-off value for a spheroid density of 10% was established, which significantly predicted overall survival. However, spheroid size did not correlate with survival outcomes. Spheroids were primarily composed of tumor cells, but the presence of lymphocytes and macrophages was also confirmed. Moreover, capillaries were present in the spheroids of three patients, but the presence of myofibroblasts was not confirmed. PD-1 was expressed on lymphocytes but not on tumor cells. PD-L1 expression was seen on both tumor and immune cells, assessed by 22C3 and SP263 antibody clones but not by the SP142 clone. Our results highlight the potential of routine cytopathological techniques to analyze spheroids in HGSC ascites as a valuable tool to investigate their potential as prognostic markers.


Assuntos
Cistadenocarcinoma Seroso , Neoplasias Ovarianas , Humanos , Feminino , Antígeno B7-H1/metabolismo , Ascite/patologia , Receptor de Morte Celular Programada 1 , Linfócitos do Interstício Tumoral , Neoplasias Ovarianas/patologia , Cistadenocarcinoma Seroso/patologia
16.
Pediatr Dermatol ; 40(6): 1028-1034, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37767822

RESUMO

BACKGROUND: Capillary malformation-arteriovenous malformation (CM-AVM) is characterized by multifocal fast-flow capillary malformations, sometimes with arteriovenous malformations/fistulas, skeletal/soft tissue overgrowth, telangiectasias, or Bier spots. Lymphatic abnormalities are infrequently reported. We describe seven patients with CM-AVM and lymphatic anomalies. METHODS: Following IRB approval, we identified patients with CM-AVM and lymphatic anomalies seen at the Vascular Anomalies Center at Boston Children's Hospital from 2003 to 2023. We retrospectively reviewed records for clinical, genetic, laboratory, and imaging findings. RESULTS: We found seven patients with CM-AVM and lymphatic abnormalities. Five patients were diagnosed prenatally: four with pleural effusions (including one suspected chylothorax) and one with ascites. Pleural effusions resolved after neonatal drainage in three patients and fetal thoracentesis in the fourth; however, fluid rapidly reaccumulated in this fetus causing hydrops. Ascites resolved after neonatal paracentesis, recurred at 2 months, and spontaneously resolved at 5 years; magnetic resonance lymphangiography for recurrence at age 19 years suggested a central conducting lymphatic anomaly (CCLA), and at age 20 years a right spermatic cord/scrotal lymphatic malformation (LM) was detected. Chylous pericardial effusion presented in a sixth patient at 2 months and disappeared after pericardiocentesis. A seventh patient was diagnosed with a left lower extremity LM at 16 months. Six patients underwent genetic testing, and all had RASA1 mutation. RASA1 variant was novel in three patients (c.1495delinsCTACC, c.434_451delinsA, c.2648del), previously reported in two (c.2603+1G>A, c.475_476del), and unavailable in another. Median follow-up age was 5.8 years (4 months-20 years). CONCLUSION: CM-AVM may be associated with lymphatic anomalies, including pericardial/pleural effusions, ascites, CCLA, and LM.


Assuntos
Fístula Arteriovenosa , Malformações Arteriovenosas , Anormalidades Linfáticas , Derrame Pleural , Masculino , Criança , Recém-Nascido , Feminino , Humanos , Adulto Jovem , Adulto , Pré-Escolar , Estudos Retrospectivos , Ascite/patologia , Proteína p120 Ativadora de GTPase/genética , Capilares/anormalidades , Malformações Arteriovenosas/genética , Derrame Pleural/patologia , Anormalidades Linfáticas/diagnóstico , Anormalidades Linfáticas/genética , Anormalidades Linfáticas/patologia , Hidropisia Fetal
17.
Dokl Biochem Biophys ; 510(1): 123-131, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37582874

RESUMO

Novel and effective treatments are urgently needed for cancer, which is still the leading cause of death in the world. Biological characteristics linked to thiazole derivatives span a wide range. Thiazole derivatives are used in the creation of medications for therapy as well. The aim of current study is to evaluate the anticancer and antioxidant properties of the newly synthesized thiazole derivatives, compounds 1 and 2, on Ehrlich ascites carcinoma (EAC) cells in female mice. Our findings indicated that thiazole derivatives, compounds 1 and 2 have anticancer activity by elevating the p53 expression and cytochrome c levels in groups treated with compounds 1 and 2 compared to the positive control group. Furthermore, thiazole derivatives compounds 1 and 2 showed a potent antioxidant effect by increasing enzymatic antioxidants, catalase (CAT) activity, and non-enzymatic antioxidants, GSH, and lowering Malondialdehyde (MDA) in hepatic and renal tissues of treated groups. Additionally, the target compounds were capable of providing corrective effects against EAC-induced biochemical and histopathological changes without harmful side effects. CONCLUSION: The target studied thiazol derivatives compounds were capable of providing corrective effects against EAC-induced without harmful side effects.


Assuntos
Carcinoma de Ehrlich , Neoplasias , Feminino , Animais , Camundongos , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Ascite/tratamento farmacológico , Ascite/patologia , Carcinoma de Ehrlich/metabolismo , Neoplasias/patologia , Fígado/metabolismo
18.
Nat Cancer ; 4(8): 1138-1156, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37488416

RESUMO

Ovarian cancer (OC) is an aggressive gynecological tumor usually diagnosed with widespread metastases and ascites. Here, we depicted a single-cell landscape of the OC ecosystem with five tumor-relevant sites, including omentum metastasis and malignant ascites. Our data reveal the potential roles of ascites-enriched memory T cells as a pool for tumor-infiltrating exhausted CD8+ T cells and T helper 1-like cells. Moreover, tumor-enriched macrophages exhibited a preference for monocyte-derived ontogeny, whereas macrophages in ascites were more of embryonic origin. Furthermore, we characterized MAIT and dendritic cells in malignant ascites, as well as two endothelial subsets in primary tumors as predictive biomarkers for platinum-based chemotherapy response. Taken together, our study provides a global view of the female malignant ascites ecosystem and offers valuable insights for its connection with tumor tissues and paves the way for potential markers of efficacy evaluation and therapy resistance in OC.


Assuntos
Ascite , Neoplasias Ovarianas , Feminino , Humanos , Ascite/patologia , Linfócitos T CD8-Positivos/patologia , Ecossistema , Análise de Célula Única
19.
Pancreas ; 52(2): e163-e167, 2023 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-37523608

RESUMO

ABSTRACT: Pancreatic mucinous cystic neoplasm (MCN) rarely ruptures because of their surrounding fibrotic capsules and has never been reported with detailed information regarding prerupture and postrupture states. We report a case of MCN rupture where performed emergency surgery was performed while waiting for elective surgery. A 54-year-old woman was referred to our department for a pancreatic cystic tumor with slight abdominal pain. A cystic tumor with a nodular lesion was found, with a contrast effect measuring 78 mm in diameter. On day 21, the patient visited our hospital complaining of increased abdominal pain, but few signs of peritonitis were observed. Tests conducted revealed moderate ascites, marginal shrinkage of the cyst diameter, and a slight elevation of inflammatory markers. We suspected an MCN rupture and immediately performed distal pancreatectomy. Brown turbid ascites and rupture of the anterior wall of the cyst were observed. In the ascites, amylase levels were not elevated, and bacterial cultures were negative. The histopathological diagnosis was noninvasive mucinous cystadenocarcinoma. At 9 months after surgery, she started chemotherapy because of a recurrence of the peritoneal dissemination. This case provided valuable insight into the rupture of MCNs using thorough imaging techniques, laboratory, and physical findings before and after rupturing.


Assuntos
Cistadenocarcinoma Mucinoso , Cistos , Neoplasias Pancreáticas , Feminino , Humanos , Pessoa de Meia-Idade , Cistadenocarcinoma Mucinoso/diagnóstico , Cistadenocarcinoma Mucinoso/cirurgia , Cistadenocarcinoma Mucinoso/patologia , Ascite/patologia , Pâncreas/patologia , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/cirurgia , Dor Abdominal , Cistos/patologia
20.
Abdom Radiol (NY) ; 48(10): 3135-3146, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37517056

RESUMO

PURPOSE: To evaluate interobserver agreement on the findings of baseline contrast-enhanced multidetector computed tomography (CE-MDCT) performed at the postoperative third month in patients who underwent surgery due to ductal adenocarcinoma of the pancreatic head and investigate the value of these findings in predicting locoregional recurrence. MATERIAL AND METHODS: The baseline CE-MDCT images of 198 patients who underwent the Whipple procedure due to pancreatic head tumors were evaluated independently by three radiologists at the postoperative third month. The radiologists were asked to note suspicious findings in terms of locoregional recurrence, including postoperative fat stranding, the presence of perivascular contrast-enhanced solid tissue, short diameter of solid tissue if present, the shape of solid tissue (convex/concave), presence of peritoneal implants, diameter (mm) of pancreatic duct dilatation if present, the presence of lymph nodes larger than 5 mm, portal vein stenosis (≥50 and <50%), the presence of ascites, and the presence of distant metastases, as specified by the Society of Abdominal Radiology in October 2022. The agreement between the radiologists and the value of these parameters in predicting locoregional recurrence were investigated. RESULTS: Among the CE-MDCT findings evaluated, the radiologists had a moderate-to-high level of agreement concerning the presence of perivascular contrast-enhanced solid tissue. However, there was a poor interobserver agreement on the shape of solid tissue. A very high level of agreement was found among the radiologists in the evaluation of pancreatic duct dilatation, peritoneal implants, ascites, and the presence of distant metastases. According to the univariate analysis, the rates of portal vein stenosis had a 1.419 -fold effect [odds ratio (OR)=1.419, [95% confidence interval (CI)= 0.548-3.679, p=0.041], lymph node presence had a 2.337 -fold effect [odds ratio (OR)=2.337, [95% confidence interval (CI)= 1.165-4.686, p=0.015], perivascular contrast-enhanced solid tissue had 2.241 -fold effect [odds ratio (OR)=2.241, [95% confidence interval (CI)= 1.072-4.684, p=0.005]. In the multivariate analysis, perivascular contrast-enhanced solid tissue had 2.241 -fold effect [odds ratio (OR)=2.519, [95% confidence interval (CI)= 1.132-5.605, p=0.024]. CONCLUSION: In the postoperative baseline CE-MDCT examination, the presence of solid tissue, lymph node presence, and portal vein stenosis in the surgical bed are among the findings that may indicate early locoregional recurrence in patients with pancreatic ductal adenocarcinoma.


Assuntos
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Humanos , Variações Dependentes do Observador , Ascite/patologia , Constrição Patológica/patologia , Tomografia Computadorizada Multidetectores/métodos , Recidiva Local de Neoplasia/patologia , Neoplasias Pancreáticas/patologia , Carcinoma Ductal Pancreático/patologia , Ductos Pancreáticos/patologia , Estudos Retrospectivos , Neoplasias Pancreáticas
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