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Malignant ascites presents a considerable clinical challenge to the management of ovarian cancer. This Opinion article discusses recent advances in our understanding of its pathophysiology, the development of new methods to characterize its molecular features and how these findings can be used to improve the treatment of malignant ascites. Malignant ascites presents a considerable clinical challenge to the management of ovarian cancer, but also provides a wealth of opportunities for translational research. The accessibility of ascitic fluid and its cellular components make it an excellent source of tumour tissue for the investigation of prognostic and predictive biomarkers, pharmacodynamic markers and for molecular profiling analysis. In this Opinion article, we discuss recent advances in our understanding of its pathophysiology, the development of new methods to characterize its molecular features and how these findings can be used to improve the treatment of malignant ascites, particularly in the context of ovarian cancer.

Most patients with ovarian cancer (OvCA) present peritoneal disseminated disease at the time of diagnosis. During peritoneal metastasis, cancer cells detach from the primary tumor and disseminate through the intraperitoneal fluid. The peritoneal mesothelial cell (PMC) monolayer that lines the abdominal cavity is the first barrier encountered by OvCA cells. Subsequent progression of tumors through the peritoneum leads to the accumulation into the peritoneal stroma of a sizeable population of carcinoma-associated fibroblasts (CAFs), which is mainly originated from a mesothelial-to-mesenchymal transition (MMT) process. A common characteristic of OvCA patients is the intraperitoneal accumulation of ascitic fluid, which is composed of cytokines, chemokines, growth factors, miRNAs, and proteins contained in exosomes, as well as tumor and mesothelial suspended cells, among other components that vary in proportion between patients. Exosomes are small extracellular vesicles that have been shown to mediate peritoneal metastasis by educating a pre-metastatic niche, promoting the accumulation of CAFs via MMT, and inducing tumor growth and chemoresistance. This review summarizes and discusses the pivotal role of exosomes and MMT as mediators of OvCA peritoneal colonization and as emerging diagnostic and therapeutic targets.

Background Differentiating advanced tubo-ovarian cancer from other malignancies in patients presenting with ascites and pelvic masses remains a critical clinical challenge. While liquid-based cytology (LBC) and serum tumor markers such as CA125 and CEA are commonly used, their diagnostic accuracy is limited. Ascitic fluid cell block (ACB) combined with immunocytochemistry (ICC) has emerged as a promising alternative, yet its comparative performance against conventional approaches—including LBC and the CA125/CEA ratio—has not been systematically evaluated in large cohorts. Methods In this retrospective study, we compared the diagnostic performance of four strategies: LBC alone, a CA125/CEA ratio > 25, LBC combined with CA125/CEA ratio > 25, and ACB combined with ICC. All methods were evaluated against histopathological findings from surgical or biopsy specimens as the reference standard. Analyses included patients with confirmed malignant ascites; a subset with complete ascitic fluid testing data was used for the primary evaluation of ACB combined with ICC. Results ACB combined with ICC demonstrated almost perfect agreement with histopathology (Cohen’s κ = 0.90). This method achieved 100% sensitivity, 81.8% specificity, a 99.2% positive predictive value, a 100% negative predictive value, and an overall diagnostic accuracy of 99.2%. Receiver operating characteristic analysis confirmed that ACB combined with ICC had significantly superior discriminative ability compared to all other evaluated methods (all P  < 0.001). Conclusion ACB combined with ICC shows near-perfect concordance with histopathological diagnosis (HIS) and exceptional diagnostic accuracy for identifying tubo-ovarian carcinoma. These results support its role as a reliable pre-treatment diagnostic tool, particularly in clinical scenarios where tissue confirmation is delayed or contraindicated, and when timely decisions regarding neoadjuvant chemotherapy are required.

Background Exosomes are nano-sized vesicles of endocytic origin that are involved in cell-to-cell communication including shuttle RNA, mainly mRNA and microRNA. As exosomes naturally carry RNA between cells, these particles might be useful in gene cancer therapy to deliver therapeutic short interfering RNA (siRNA) to the target cells. Despite the promise of RNA interference (RNAi) for use in therapy, several technical obstacles must be overcome. Exogenous siRNA is prone to degradation, has a limited ability to cross cell membranes and may induce an immune response. Naturally occurring RNA carriers, such as exosomes, might provide an untapped source of effective delivery strategies. Results This study demonstrates that exosomes can deliver siRNA to recipient cells in vitro . The different strategies were used to introduce siRNAs into human exosomes of various origins. The delivery of fluorescently labeled siRNA via exosomes to cells was confirmed using confocal microscopy and flow cytometry. Two different siRNAs against RAD51 and RAD52 were used to transfect into the exosomes for therapeutic delivery into target cells. The exosome-delivered siRNAs were effective at causing post-transcriptional gene silencing in recipient cells. Moreover, the exosome-delivered siRNA against RAD51 was functional and caused the massive reproductive cell death of recipient cancer cells. Conclusions The results strongly suggest that exosomes effectively delivered the siRNA into the target cells. The therapeutic potential of exosome-mediated siRNA delivery was demonstrated in vitro by the strong knockdown of RAD51 , a prospective therapeutic target for cancer cells. The results give an additional evidence of the ability to use human exosomes as vectors in cancer therapy, including RNAi-based gene therapy.

Spontaneous bacterial peritonitis (SBP) is associated with high mortality. Early paracentesis (EP) is essential for rapid diagnosis and optimal treatment. The aim of the study is to compare the outcomes of patients with SBP who received EP vs. delayed paracentesis (DP). Consecutive patients who were diagnosed with SBP (ascites neutrophil count ≥250 cells/mm(3) and clinical evidence of cirrhosis) <72 h from the first physician encounter at two centers were identified. EP was defined by receiving paracentesis <12 h and DP 12-72 h from hospitalization. Primary outcome was in-hospital mortality. The mean age of 239 patients with SBP was 53±10 years; mean Model for End-Stage Liver Disease (MELD) score was 22±9. In all, 98 (41%) patients who received DP had a higher in-hospital mortality (27% vs. 13%, P=0.007) compared with 141 (59%) who received EP. Furthermore, DP group had longer intensive care days (4.0±9.5 vs. 1.3±4.1, P=0.008), hospital days (13.0±14.7 vs. 8.4±7.4, P=0.005), and higher 3-month mortality (28/76, 37% vs. 21/98, 21%; P=0.03) compared with the EP group. Adjusting for MELD score ≥22 (adjusted odds ratio (AOR)=5.7, 95% confidence interval (CI)=1.8-18.5) and creatinine levels ≥1.5 mg/dl (AOR=3.2, 95% CI=1.4-7.2), DP was associated with increased in-hospital mortality (AOR=2.7, 95% CI=1.3-4.8). Each hour delay in paracentesis was associated with a 3.3% (95% CI=1.3-5.4%) increase in in-hospital mortality after adjusting for MELD score and creatinine levels. Hospitalized patients with SBP who received DP had a 2.7-fold increased risk of mortality adjusting for MELD score and renal dysfunction. Diagnostic paracentesis performed <12 h from hospitalization in patients with cirrhosis and ascites may improve short-term survival.

Abstract Background The relationship between fluid characteristics and cause of cavitary effusions is incompletely characterized. Hypothesis/Objectives Describe fluid characteristics and cytologic classification of cavitary effusions in dogs and cats. Animals A total of 269 dogs and 107 cats with cytologic fluid analysis of cavitary effusion. Methods Retrospective medical record review (2016–2020). Differences among groups were assessed using Kruskal–Wallis testing with post hoc pairwise Dunn's or Fisher's Exact testing. Results In dogs, peritoneal transudates most frequently were caused by decreased oncotic pressure (DOP; 63%, p < 0.001) and modified transudates by increased hydrostatic pressure (IHP; 41%, p < 0.001). Peritoneal exudates more frequently were caused by increased vascular permeability (IVP; 40%), ruptured viscera (35%), or neoplasia (23%) compared with IHP or DOP (p < 0.01 for all). Pleural transudates in dogs most frequently were caused by DOP (79%, p < 0.001) and modified transudates by IHP (33%) or neoplasia (29%). Pleural exudates were more likely to be caused by neoplasia (52%) or IVP (36%) compared with IHP or DOP (p < 0.001). In cats, peritoneal effusions commonly were caused by IVP or neoplasia, and pleural effusions by IHP or neoplasia. No statistical relationship was found between cytologic category and cause of effusion in cats. Conclusions and Clinical Importance Cytologic classification and fluid characteristics are most predictive of disease process in peritoneal effusions in dogs, whereas effusions in cats have substantial overlap across causes.

Endometriosis is a gynecological condition that is associated with chronic pelvic inflammation, pain, and infertility. Although substantial evidence supports that immunological alterations contribute to its pathogenesis and we previously posed a pivotal role of Galectin-9 (Gal-9) in this disorder, the involvement of the TIM-3/Gal-9 pathway in the development of endometriosis-associated immunological abnormalities is not yet known. In the present study, multicolor flow cytometry was used to compare the immunophenotype and cell surface expression of TIM-3 and Gal-9 molecules on peripheral blood (PB) and peritoneal fluid (PF) lymphocytes of women with and without endometriosis. We found an altered distribution of different lymphocyte subpopulations, a markedly decreased TIM-3 labeling on all T and NK subsets and a significantly increased Gal-9 positivity on peripheral CD4+ T and Treg cells of the affected cohort. Furthermore, a significantly increased TIM-3 expression on CD4+T-cells and elevated Gal-9 labeling on all T and NK subsets was also revealed in the PF of the examined patients. In conclusion, our results suggest a persistent activation and disturbed TIM-3/Gal-9-dependent regulatory function in endometriosis, which may be involved in the impaired immune surveillance mechanisms, promotes the survival of ectopic lesions, and aids the evolution of reproductive failures in endometriosis.

Bacterial infections, most commonly spontaneous bacterial peritonitis in patients with ascites, occur in one third of admitted patients with cirrhosis, and account for a 4-fold increase in mortality. Bacteria are isolated from less than 40% of ascites infections by culture, necessitating empirical antibiotic treatment, but culture-independent studies suggest bacteria are commonly present, even in the absence of overt infection. Widespread detection of low levels of bacteria in ascites, in the absence of peritonitis, suggests immune impairment may contribute to higher susceptibility to infection in cirrhotic patients. However, little is known about the role of ascites leukocyte composition and function in this context. We determined ascites bacterial composition by quantitative PCR and 16S rRNA gene sequencing in 25 patients with culture-negative, non-neutrocytic ascites, and compared microbiological data with ascites and peripheral blood leukocyte composition and phenotype. Bacterial DNA was detected in ascitic fluid from 23 of 25 patients, with significant positive correlations between bacterial DNA levels and poor 6-month clinical outcomes (death, readmission). Ascites leukocyte composition was variable, but dominated by macrophages or T lymphocytes, with lower numbers of B lymphocytes and natural killer cells. Consistent with the hypothesis that impaired innate immunity contributes to susceptibility to infection, high bacterial DNA burden was associated with reduced major histocompatibility complex class II expression on ascites (but not peripheral blood) monocytes/macrophages. These data indicate an association between the presence of ascites bacterial DNA and early death and readmission in patients with decompensated cirrhosis. They further suggest that impairment of innate immunity contributes to increased bacterial translocation, risk of peritonitis, or both.

[...]patients with presinusoidal portal hypertension without cirrhosis rarely develop ascites. [...]patients do not develop ascites with isolated chronic extrahepatic portal venous occlusion or non-cirrhotic causes of portal hypertension such as congenital hepatic fibrosis, except following an insult to liver function such as gastrointestinal haemorrhage. [...]the old concept that ascites is formed secondary to decreased oncotic pressure is false, and plasma albumin concentrations have little influence on the rate of ascites formation.

Background Minimal residual disease of the peritoneum is challenging for early cancer detection in gastric cancer (GC). Utility of PCR amplification of cancer-derived DNA has been considered feasible due to its molecular stability, however such markers have never been available in GC clinics. We recently discovered cancer-specific methylation of CDO1 gene in GC, and investigated the clinical potential to detect the minimal residual disease. Methods One hundred and two GC patients were investigated for peritoneal fluid cytology test (CY), and detection level of the promoter DNA methylation of CDO1 gene was assessed by quantitative methylation specific PCR (Q-MSP) in the sediments (DNA CY). Results (1) CY1 was pathologically confirmed in 8 cases, while DNA CY1 was detected in 18 cases. All 8 CY1 were DNA CY1. (2) DNA CY1 was recognized in 14.3, 25.0, 20.0, and 42.9%, in macroscopic Type II, small type III, large type III, and type IV, respectively, while it was not recognized in Type 0/I/V. (3) DNA CY1 was prognostic relevance in gastric cancer ( p  = 0.0004), and its significance was robust among Type III/IV gastric cancer ( p  = 0.006 for overall survival and p  = 0.0006 for peritoneal recurrence free survival). (4) The peritoneal recurrence was hardly seen in GC patients with potent perioperative chemotherapy among those with DNA CY1. Conclusions DNA CY1 detected by Q-MSP for CDO1 gene promoter DNA methylation has a great potential to detect minimal residual disease of the peritoneum in GC clinics as a novel DNA marker.