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Genes Dec 2022Epithelial ovarian cancer (EOC) is the main cause of mortality among gynecological malignancies worldwide. Although patients with EOC undergo aggregate treatment, the...
Epithelial ovarian cancer (EOC) is the main cause of mortality among gynecological malignancies worldwide. Although patients with EOC undergo aggregate treatment, the prognosis is often poor. Peritoneal malignant ascites is a distinguishable clinical feature in EOC patients and plays a pivotal role in tumor progression and recurrence. The mechanisms of the tumor microenvironment (TME) in ascites in the regulation of tumor progression need to be explored. We comprehensively analyzed the transcriptomes of 4680 single cells from five EOC patients (three diagnostic samples and two recurrent samples) derived from Gene Expression Omnibus (GEO) databases. Batch effects between different samples were removed using an unsupervised deep embedding single-cell cluster algorithm. Subcluster analysis identified the different phenotypes of cells. The transition of a malignant cell state was confirmed using pseudotime analysis. The landscape of TME in malignant ascites was profiled during EOC progression. The transformation of epithelial cancer cells into mesenchymal cells was observed to lead to the emergence of related anti-chemotherapy and immune escape phenotypes. We found the activation of multiple biological pathways with the transition of tumor-associated macrophages and fibroblasts, and we identified the infiltration of CD4CD25 T regulatory cells in recurrent samples. The cell adhesion molecules mediated by integrin might be associated with the formation of the tumorsphere. Our study provides novel insights into the remodeling of the TME heterogeneity in malignant ascites during EOC progression, which provides evidence for identifying novel therapeutic targets and promotes the development of ovarian cancer treatment.
Topics: Female; Humans; Carcinoma, Ovarian Epithelial; Transcriptome; Ascites; Tumor Microenvironment; Neoplasms, Glandular and Epithelial; Ovarian Neoplasms
PubMed: 36553542
DOI: 10.3390/genes13122276 -
Asian Journal of Surgery Jan 2020Etiology of ascites of unknown origin varies with geographic area and ethnic origin. Tuberculous peritonitis and peritoneal carcinomatosis constitute a considerable... (Review)
Review
Etiology of ascites of unknown origin varies with geographic area and ethnic origin. Tuberculous peritonitis and peritoneal carcinomatosis constitute a considerable proportion of patients. Differentiation between both is a major challenge. The role of omental thickness (OT) by ultrasonography to predict risk of malignancy in unexplained ascites. This prospective study was done at Kasr Alainy School of Medicine, Cairo University and included 100 adults with unexplained ascites and thickened omentum (>15 mm) on ultrasonography. An expert performed ultrasonography to assess peritoneum and peritoneal cavity and measure OT. Ascites was assessed regarding volume, echogenicity, and loculation. The ascitic fluid was analyzed to measure lactate dehydrogenase, adenosine deaminase, and total leukocytic count. Laparoscopic exploration with biopsy was done for final diagnosis that divided the patients into; TB Group (n = 44) and peritoneal carcinomatosis group (n = 56). Main Outcome Measures were to determine degree of omental thickness as a predictor of malignancy risk in unexplained ascites and other ultrasonographic features to predict malignancy risk including omental echogenicity and results of diagnostic ascitic tapping. We found that OT was greater in the PC group compared to the TB group (24.6 ± 4.6 mm vs. 17.9 ± 3.0 mm, respectively, p < 0.001). Higher frequency of hypoechogenicity, irregular peritoneal surface, omental cakes, and lymph nodes was seen in PC Group. ADA, TLC, and relative lymphocyte count were higher in TB group. Omental thickness ≥19.5 mm has a sensitivity of 89.3%, specificity of 84.1% to diagnose PC. We can conclude that omental thickness >19 mm is a sensitive and specific predictor of malignancy in patients with unexplained ascites.
Topics: Aged; Ascites; Egypt; Female; Humans; Male; Middle Aged; Omentum; Predictive Value of Tests; Risk; Ultrasonography
PubMed: 30910377
DOI: 10.1016/j.asjsur.2019.03.004 -
The Israel Medical Association Journal... Apr 2002
Topics: Ascites; Cysts; Diagnosis, Differential; Humans
PubMed: 12001718
DOI: No ID Found -
BMC Genomics Jun 2024Peritoneal carcinomatosis was the main reason leading to gastric cancer (GC)-related death. We aimed to explore the roles of dysregulated microRNAs (miRNAs) and related...
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.
Topics: Humans; MicroRNAs; Stomach Neoplasms; Ascites; Prognosis; Biomarkers, Tumor; Gene Expression Profiling; Gene Regulatory Networks; Gene Expression Regulation, Neoplastic; RNA, Messenger
PubMed: 38914980
DOI: 10.1186/s12864-024-10359-2 -
ESMO Open Dec 2023Identification of factors associated with survival after ascites diagnosis in metastatic pancreatic cancer (mPC) patients may guide treatment decisions and help to...
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.
Topics: Humans; Retrospective Studies; Ascites; Quality of Life; Pancreatic Neoplasms; Liver Neoplasms
PubMed: 37977000
DOI: 10.1016/j.esmoop.2023.102048 -
Oncology 2012
Topics: Ascites; Female; Humans; Male; Octreotide; Peritoneal Neoplasms
PubMed: 22572796
DOI: 10.1159/000337690 -
Arquivos de Gastroenterologia 2022The role of ascitic and serum levels of various tumour biomarkers in the discrimination of cause of ascites is not well established.
BACKGROUND
The role of ascitic and serum levels of various tumour biomarkers in the discrimination of cause of ascites is not well established.
OBJECTIVE
To evaluate the role of serum and ascitic levels of tumor biomarkers (CA 72-4, CA 19-9, CEA and CA 125) in discrimination of cause of ascites.
METHODS
A prospective study was conducted in consecutive patients presenting with ascites. Serum and ascitic levels of CA 19-9, CA 125, CA 72-4 and carcinoembryonic antigen (CEA) were determined at the presentation. The patients with cirrhotic ascites, tuberculous peritonitis (TBP) and peritoneal carcinomatosis (PC) were eventually included in analysis.
RESULTS
Of the 93 patients (58 males, mean age 47 years) included, the underlying cause was cirrhosis in 31, PC in 42 and peritoneal tuberculosis in 20. The best cutoff for discriminating benign and malignant ascites for serum CEA, CA 19-9 and CA 72-4 were 6.7 ng/mL, 108 IU/mL and 8.9 IU/mL, respectively. The best cutoff for discriminating benign and malignant ascites for ascitic CA 125, CEA, CA 19-9 and CA 72-4 were 623 IU/mL, 8.7 ng/mL, 33.2 IU/mL and 7 IU/mL, respectively.
CONCLUSION
The performance of single biomarker for the prediction of underlying PC is low but a combination of serum CA 19-9 and CA 72-4 best predicted the presence of peritoneal carcinomatosis.
Topics: Ascites; Ascitic Fluid; Biomarkers, Tumor; Carcinoembryonic Antigen; Female; Humans; Male; Middle Aged; Peritoneal Neoplasms; Prospective Studies
PubMed: 35830029
DOI: 10.1590/S0004-2803.202202000-37 -
The Journal of International Medical... Feb 2021This prospective, dose-escalation phase I study evaluated the safety and efficacy of intraperitoneal bevacizumab in managing refractory malignant ascites and explored...
OBJECTIVE
This prospective, dose-escalation phase I study evaluated the safety and efficacy of intraperitoneal bevacizumab in managing refractory malignant ascites and explored the recommended dose of bevacizumab for further study.
METHODS
Patients with refractory malignant ascites were enrolled. Bevacizumab was intraperitoneal administered weekly at an initial dose of 2.5 mg/kg, with dose escalation to 5 and 7.5 mg/kg performed following the standard "3 + 3" rule. The total duration of treatment was 2 or 3 weeks.
RESULTS
Between December 2013 and September 2014, 13 patients (2.5 mg/kg, n = 4; 5 mg/kg, n = 3; 7.5 mg/kg, n = 6) with refractory malignant ascites were enrolled. Bevacizumab was well tolerated, and the most common treatment-related adverse events were abdominal pain (5/13), abdominal distension (2/13), and fatigue (2/13). The dose-limiting toxicity at 7.5 mg/kg was grade 3 bowel obstruction (1/13). The maximum tolerated dose (MTD) was not reached. The overall response and disease control rates were 7.7 and 61.5%, respectively.
CONCLUSIONS
Intraperitoneal bevacizumab safe and well tolerated for treating malignant ascites, and the MTD was not reached at doses of 2.5 to 7.5 mg/kg. Intraperitoneal bevacizumab at 7.5 mg/kg weekly is recommended for further study to verify its anti-tumor activity. Clinical Trials NCT01852409.
Topics: Antineoplastic Combined Chemotherapy Protocols; Ascites; Bevacizumab; Humans; Maximum Tolerated Dose; Peritoneal Neoplasms; Prospective Studies
PubMed: 33616416
DOI: 10.1177/0300060520986664 -
BioMed Research International 2017Here we examined whether malignant ascites may determine ovarian tumor angiogenesis, and if so whether ascites generated by highly aggressive serous and undifferentiated...
Here we examined whether malignant ascites may determine ovarian tumor angiogenesis, and if so whether ascites generated by highly aggressive serous and undifferentiated cancers are more proangiogenic than those from less aggressive clear cell and endometrioid tumors. Angiogenesis was analyzed according to expression of CD31, CD34, and connexin 43. Proliferation and migration of endothelial cells were tested using fluorescence-based methods. The quantification of angiogenic agents and hypoxia-inducible factor 1 (HIF-1) was performed using specific immunoassays. Results showed that the expression of CD31 and CD34 in serous and undifferentiated tumors was greater, whereas endothelial expression of connexin 43 was lower than in clear cell and endometrioid lesions. Serous cancers that formed in the presence of ascites displayed increased expression of connexin 43 in vascular smooth muscles as compared with tumors developed in the fluid's absence. Endothelial cells exposed to ascites from serous and undifferentiated tumors proliferated and migrated more vigorously than cells subjected to ascites from clear cell and endometrioid cancers. They also exhibited an increased level of HIF-1 and produced increased amounts of multiple proangiogenic agents. Our results indicate that high vascularization of aggressive ovarian tumors may be associated with profound angiogenic capabilities of ascites generated by these tumors.
Topics: Ascites; Female; Gene Expression Regulation, Neoplastic; Humans; Neoplasm Proteins; Neovascularization, Pathologic; Ovarian Neoplasms
PubMed: 29085834
DOI: 10.1155/2017/2592496 -
Technology and Health Care : Official... 2023There is a need for an improved version of the implantable catheter for malignant ascites in the abdominal cavity.
BACKGROUND
There is a need for an improved version of the implantable catheter for malignant ascites in the abdominal cavity.
OBJECTIVE
New implantable catheters have been developed that drain ascites from the abdominal cavity to the bladder by applying pressure. Based on pigtail catheters, these newly designed catheters have silicone membranes and apertures.
METHODS
Experimental instruments controlled flow rates and water level to observe changes of the activation pressure and its cycle time along flow rates and turns of catheters. Furthermore, various normality tests, difference tests and non-parametric tests were investigated to observe statistical validity.
RESULTS
Cycle times were significantly affected by flow rate (3/4 cases of p< 0.05). The effects of flow rate on activation pressure, however, were not significant (1/4 case of p< 0.05). Cycle times were not significantly affected by the number of turns of the catheter (3/8 cases of p< 0.05). In contrast, the effects of the turns on activation pressure were significant (5/8 cases of p< 0.05).
CONCLUSION
Overall, there was no significant difference between cycle times for 1.5 turns and 2.0 turns of catheters. In addition, catheters with 1.5 turns have a lower activation pressure than catheters with 2.0 turns. It is possible to customize catheters based on the ascites excretion and urination rates of various terminal patients.
Topics: Humans; Ascites; Catheters, Indwelling; Drainage; Neoplasms; Urinary Bladder
PubMed: 37038794
DOI: 10.3233/THC-236019