Ascitic Levels Research Articles

SB7-H4 is a diagnostic biomarker in epithelial ovarian cancer and correlates to platinum resistance.

Ovarian cancer, with its high mortality rate among gynecological cancers, is often diagnosed late due to the lack of early diagnostic symptoms and biomarkers. The tumor immune microenvironment has become a focal point in cancer diagnostic and therapeutic research. Among these, B7-H4, a checkpoint protein, plays a crucial role in immune regulation and tumor suppression, contributing to immune evasion within the tumor microenvironment. This study aims to identify the concentration of soluble B7-H4(sB7-H4) in the plasma of patients with ovarian cancer and to evaluate its clinical significance. Through a comprehensive analysis involving enzyme-linked immunosorbent assay, immunohistochemistry, and multicolor immunofluorescence, we quantified sB7-H4 levels in patient plasma and ascites, correlating these findings with tissue expression and clinical outcomes. Results indicated a strong association between high sB7-H4 levels and advanced disease, surgical outcomes, lymphatic metastasis, and platinum resistance. When compared with traditional biomarkers CA125 and HE4, sB7-H4, especially in conjunction with these markers, enhances the diagnostic accuracy for epithelial ovarian cancer, offering insights into disease progression and therapeutic efficacy. This comprehensive analysis suggests that sB7-H4 is a promising biomarker for EOC, providing valuable insights into diagnosis, stage differentiation, treatment effectiveness, and prognosis.

PD-L1+ neutrophils induced NETs in malignant ascites is a potential biomarker in HCC

BackgroundSince differentiating malignant ascites from benign ascites has always been a clinical difficult, recognition of novel biomarkers in malignant ascites of hepatocellular carcinoma (HCC) patients could be helpful for establishing a diagnosis for HCC patients with ascitic fluids.MethodsThirty-five HCC patients with malignant ascites and chronic liver diseases patients with benign ascites were enrolled. Serum and ascites specimens were collected to determine TAN subpopulations and NETs concentration. Then, the correlation between ascitic NETs levels and clinical features were analyzed, and ROC curves were generated to evaluate the diagnostic value of NETs. For in vitro study, fresh neutrophils were employed to explore the underlying mechanism of TAN polarization and NETs formation using RNAseq analysis.ResultsSignificantly increased pro-tumor PD-L1+ TANs and higher lactate levels were measured in HCC ascites. RNAseq data showed that lactate regulated genes expression involving PD-L1 expression and NETs formation, suggesting that ascitic lactate might be responsible for tumor progression in TME. Then, NETs-related markers including calprotectin, dsDNA, CitH3, MPO and MPO-DNA were found dramatically elevated in malignant ascites. Next, correlation analysis revealed that ascitic NETs levels positively correlated with LDH, a classic ascitic biochemical indicator. Furthermore, we identified the diagnostic values of NETs in discriminating malignant ascites from benign ascites.ConclusionsOur findings highlighted that elevated ascitic NETs served as a biomarker in HCC patients with malignant ascites, which provided useful insights for both clinical and basic research for malignant ascites diagnosis and management.

Analysis of ATP7A Expression and Ceruloplasmin Levels as Biomarkers in Patients Undergoing Neoadjuvant Chemotherapy for Advanced High-Grade Serous Ovarian Carcinoma.

Ovarian cancer (OC), particularly high-grade serous carcinoma (HGSC), is a leading cause of gynecological cancer mortality due to late diagnosis and chemoresistance. While studies on OC cell lines have shown that overexpression of the ATP7A membrane transporter correlates with resistance to platinum-based drugs (PtBMs) and cross-resistance to copper (Cu), clinical evidence is lacking. The functionality of ceruloplasmin (CP), the main Cu-transporting protein in the blood, is dependent on, among other things, ATP7A activity. This study investigated ATP7A expression and CP levels as potential biomarkers for predicting responses to PtBMs. We included 28 HGSC patients who underwent neoadjuvant chemotherapy (NACT). ATP7A expression in ovarian and peritoneal tissues before NACT and in peritoneal and omental tissues after NACT was analyzed via qPCR, and CP levels in ascites and plasma were measured via ELISA before and after NACT. In total, 54% of patients exhibited ATP7A expression in pretreatment tissue (ovary and/or peritoneum), while 43% of patients exhibited ATP7A expression in tissue after treatment (peritoneum and/or omentum). A significant association was found between higher ATP7A expression in the peritoneum before NACT and an unfavorable CA-125 elimination rate constant k (KELIM) score. Patients with omental ATP7A expression had significantly higher plasma mean CP levels before NACT. Plasma CP levels decreased significantly after NACT, and higher CP levels after NACT were associated with a shorter platinum-free interval (PFI). These findings suggest that the ATP7A transporter and CP have the potential to serve as predictive markers of chemoresistance, but further research is needed to validate their clinical utility.

Ascites and Serum Interleukin-10 Levels as a Prognostic Tool for Ovarian Cancer Outcomes.

Interleukin-10 (IL-10) has been shown to be present at high levels in the ascites of ovarian cancer (OC) patients; however, little is known about its prognostic value. We sought to correlate IL-10 levels in ascites and sera of OC patients with clinicopathologic characteristics and oncologic outcomes. IL-10 levels and clinical data from biobanked ascites and serum samples of OC patients were evaluated. Receiver operating characteristic curves were used to quantify marker performance and identify IL-10-high and IL-10-low groups. Correlations between IL-10 levels and clinicopathologic data were performed. Survival outcomes were calculated, while the factors affecting them were also investigated. A total of 106 patients had ascites samples, of which 44 serum samples were also available. Mean ascites IL-10 levels were significantly higher in patients with serous histology compared to endometrioid histology (p = 0.024). Fold-change in ascites IL-10 during treatment positively correlated with clinical response, as determined by a change in serum cancer antigen (CA)-125 levels (p = 0.0126). Median progression-free survival (PFS) and overall survival (OS) were shorter in patients with high compared with low ascites IL-10 levels (PFS: 18 versus 60 months; p = 0.007, OS: 42 versus 85 months; p = 0.029). A significant positive correlation was seen between ascites and sera IL-10 levels (p = 0.019). In multivariable analyses, a high ascites IL-10 level was associated with a significantly worse prognosis (PFS hazard ratio (HR) = 1.93; p = 0.02). Patients with high ascites levels of IL-10 have worse outcomes, which are likely reflective of the immunosuppressive effect of IL-10. This highlights its potential role as an immunomodulator in the tumor microenvironment, leading to OC immune evasion.

Ascitic ENDOCAN as a Useful Marker in the Diagnosis of Spontaneous Bacterial Peritonitis

Abstract Background Spontaneous bacterial peritonitis (SBP) is a serious, recurrent, and life-threatening condition developing in cirrhotic patients with a high mortality rate. Its diagnosis is based on ascitic fluid polymorphonuclear leukocytes (PMNs) to be more than 250/μL. Endocan is a proteoglycan (PG) secreted by vascular endothelium, its serum level is elevated with an inflammatory or a malignant process. Aim of the Work to evaluate the potential role of ascitic fluid levels of endocan as an appropriate marker for prediction and early diagnosis of spontaneous bacterial peritonitis in patients with liver cirrhosis. Patients and Methods This was Prospective cohort study, was conducted in hepatology Unit of Ain Shams University Hospital over 100 patients with liver cirrhosis classified into two groups: (Non-SBP): included 50 patients of decompensated cirrhosis with sterile (non SBP) ascites, (SBP): included 50 Adult patients with liver cirrhosis and SBP, during a Period 6 months. All patients were subjected to: Full history taking, Clinical examination, Routine investigations, Radiology investigations, Determination of ascitic endocan levels by ELISA. Result The main results of the study revealed that: There was no statistically significant difference between the studied groups as regard personal data. There was a high statistically significant difference between the studied groups as regardsChild-Pugh score. There was no statistically significant difference between the studied groups as regard LFT. There was statistically significant difference between the studied groups as regard WBCs. There was statistically significant difference between the studied groups as regard INR. There was no statistically significant difference between the studied groups as regard creatinine. There was statistically significant difference between the studied groups as regard Ascetic endocan. Conclusion In conclusion, this study demonstrates that ascitic endocan level is an independent risk factor for SBP and has a high diagnostic value for detecting SBP in patients with decompensated cirrhosis.

Use of Bacterial DNA Concentration in Ascites as a Marker for Spontaneous Bacterial Peritonitis

Background & AimsSpontaneous bacterial peritonitis (SBP) is a common and serious complication in patients with decompensated cirrhosis. Precise quantification of bacterial DNA (bactDNA) and the related inflammatory response might add further information on the course of disease. The aim of the study was to evaluate the association between bactDNA, cytokine levels and clinical outcome. MethodsAscites and serum samples of 98 patients with decompensated liver cirrhosis (42 with SBP and 56 without SBP) as well as serum samples of 21 healthy controls were collected. BactDNA in ascites and serum was detected and quantified by 16S rRNA PCR. Concentrations of IL-1β, TNF-α, IL-6, IL-8 and IL-10 were measured by a LEGENDplexTM multi-analyte flow assay. Clinical data were collected and analyzed retrospectively. ResultsBactDNA was detected more frequently in ascites of patients with SBP (n=24/42; 57.1%) than in ascites of patients without SBP (n=5/56; 8.9%; p < 0.001). Additionally, IL-6 levels in both ascites and serum were significantly higher in patients with SBP (ascites p < 0.001, serum p = 0.036). The quantity of bactDNA in ascites was strongly correlated with polymorphonuclear neutrophil count in ascites (r = 0.755; p < 0.001) as well as ascites IL-6 levels (r = 0.399; p < 0.001). Receiver operating characteristic (ROC) curve analysis to diagnose SBP provided an AUC of 0.764 (95% CI: 0.661 – 0.867) for serum IL-6 levels, an AUC of 0.810 (95% CI: 0.714 - 0.905) for ascites IL-6 levels, and an AUC of 0.755 (95% CI: 0.651 – 0.858) for bactDNA levels in ascites. ConclusionsThe correlation between the amount of bactDNA and IL-6 confirms the pathophysiological relevance of bactDNA and IL-6 as potential biomarkers for the diagnosis of SBP.

Pre-operative plasma VEGF-C levels portend recurrence in epithelial ovarian cancer patients and is a bankable prognostic marker even in the initial assessment of a patient

PurposeOur explorative study assessed a panel of molecules for their association with epithelial ovarian carcinomas and their prognostic implications. The panel included tissue expression of VEGF-C, COX-2, Ki-67 and eNOS alongside plasma levels of VEGF-C and nitric oxide.Methods130 cases were enrolled in the study. Plasma levels were quantified by ELISA and tissue expressions were scored by immunohistochemistry. The Chi square and Fischer’s exact test were applied to examine the impact of markers on clinicopathological factors. Non-parametric Spearman’s rank correlation test was applied to define the association among test factors.ResultsPlasma VEGF-C levels and COX-2 tissue expression strongly predicted recurrence and poor prognosis (< 0.001). Tissue Ki-67 was strongly indicative of late-stage disease (< 0.001). The aforementioned markers significantly associated with clinicopathological factors. Nuclear staining of VEGF-C was intriguing and was observed to correlate with high grade-stage malignancies, highly elevated plasma VEGF-C, and with recurrence. eNOS tissue expression showed no significant impact while nitric oxide associated positively with ascites levels. Tissue expression of VEGF-C did not associate significantly with poor prognosis although the expression was highly upregulated in most of the cases.ConclusionPlasma VEGF-C holds immense promise as a prognostic marker and the nuclear staining of VEGF-C seems to have some significant implication in molecular carcinogenesis and is a novel finding that commands further robust scrutiny. We present a first such study that assesses a set of biomarkers for prognostic implications in clinical management of epithelial ovarian carcinomas in a pan-Indian (Asian) population.

The IGF-PAPP-A-Stanniocalcin Axis in Serum and Ascites Associates with Prognosis in Patients with Ovarian Cancer.

Pregnancy-associated plasma protein-A (PAPP-A) and PAPP-A2 modulate insulin-like growth factor (IGF) action and are inhibited by the stanniocalcins (STC1 and STC2). We previously demonstrated increased PAPP-A and IGF activity in ascites from women with ovarian carcinomas. In this prospective, longitudinal study of 107 women with ovarian cancer and ascites accumulation, we determined corresponding serum and ascites levels of IGF-1, IGF-2, PAPP-A, PAPP-A2, STC1, and STC2 and assessed their relationship with mortality. As compared to serum, we found highly increased ascites levels of PAPP-A (51-fold) and PAPP-A2 (4-fold). Elevated levels were also observed for IGF-1 (12%), STC1 (90%) and STC2 (68%). In contrast, IGF-2 was reduced by 29% in ascites. Patients were followed for a median of 38.4 months (range: 45 days to 8.9 years), during which 73 patients (68.2%) died. Overall survival was longer for patients with high serum IGF-1 (hazard ratio (HR) per doubling in protein concentration: 0.60, 95% CI: 0.40-0.90). However, patients with high ascites levels of IGF-1 showed a poorer prognosis (HR: 2.00 (1.26-3.27)). High serum and ascites IGF-2 levels were associated with increased risk of mortality (HR: 2.01 (1.22-3.30) and HR: 1.78 (1.24-2.54), respectively). Similarly, serum PAPP-A2 was associated with mortality (HR: 1.26 (1.08-1.48)). Our findings demonstrate the presence and activity of the IGF system in the local tumor ecosystem, which is likely a characteristic feature of malignant disease and plays a role in its peritoneal dissemination. The potential clinical implications are supported by our finding that serum levels of the proteins are associated with patient prognosis.

Ascitic Fluid Lactate Level as a Predictor of Mortality in Cirrhotic Patients Having Spontaneous Bacterial Peritonitis (SBP).

Introduction Limited studies are available for predicting mortality in patients with spontaneous bacterial peritonitis (SBP) based on ascitic fluid analysis. Recently, a proposition has been made regarding the role of ascitic fluid lactate as a better prognostic indicator of mortality in cirrhotic patients with SBP. Therefore, we aimed to evaluate the utility of ascitic fluid lactate in predicting mortality in cirrhotic patients with SBP. Methods This was a prospective, observational study that was conducted in the Hepato-Gastroenterology Department of Sindh Institute of Urology and Transplantation (SIUT), Karachi from 1January2022 to 31December 2022.All the patients having liver cirrhosis with ascites, aged between 18 and 65 years, and presenting with fever and/or abdominal pain were recruited in the study in the first six months (i.e., from 1January 2022 to 30June 2022) and were followed for sixmore months for the outcome. However, those patients on dialysis or those with hepatocellular carcinoma,any other malignancy as per a history of solid organ transplant, a history of HIV infection, or thoseunderlying systemic sepsis or infections other than SBP were excluded from the study. The presence or absence of SBP was confirmed by doing the ascitic fluid analysis. Ascitic fluid lactate levels were also requested in each patient. Mortality was assessed at one, two, three, and six months, respectively. All the data were analyzed using SPSS version 23.0. The area under the receiver operating curve(AUROC) was obtained for ascitic fluid lactate for predicting mortality in SBP. At an optimal cutoff, the diagnostic accuracy of ascitic fluid lactate was obtained. Results The total number of cirrhotic patients included in the study was 123. The majority of the patients belong to Child Turcotte Pugh (CTP) class C (n = 88; 71%). Two third of the patients (65.8%; n = 81) had viral hepatitis i.e., hepatitis B, D, and/or C, as the cause of cirrhosis. Overall mortality was observed in 51(41.5%) patients. Ascitic fluid lactate was significantly raised in patients with SBP than in patients with non-SBP (p = 0.004). The AUROC of ascitic fluid lactate was highest at three months (AUROC = 0.88) followed by six months (AUROC = 0.84), two months (AUROC = 0.804), and one month (AUROC=0.773). At an optimal cut-off of more than or equal to 22.4 mg/dl, ascitic fluid lactate had a sensitivity of 84.9%, specificity of 85.7%, positive predictive value (PPV) of 97.3%, negative predictive value of 42.8% with diagnostic accuracy of 85% in predicting overall mortality in patients with SBP. On sub-analysis, the diagnostic accuracy of ascitic fluid lactate was highest at six months followed by at three, two, and one month, respectively. Conclusion Ascitic fluid lactate showed a good diagnostic utility in predicting the overall mortality in patients with SBP with the best diagnostic accuracy in predicting long-term (six months) mortality. However, further studies are required to validate our results.

Ascites fluid calprotectin level is highly accurate in diagnosing spontaneous bacterial peritonitis: a preliminary proof of concept prospective study

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.

Diagnosis and treatment of hepatorenal syndrome; a systematic review

Hepatorenal syndrome (HRS) is a severe form of functional renal failure associated with reduced renal blood flow, predominantly affecting patients with ascites and cirrhosis, showcasing normal kidney histology. This complication of advanced liver disease is marked by a grim prognosis, with survival typically spanning weeks or months. Diagnosis hinges on a blend of clinical and laboratory criteria, given the absence of definitive biomarkers. This systematic study sought to formulate guidelines for HRS diagnosis and treatment. Data, drawn from PubMed/Medline, Scopus databases, and Embase, encompassed English-language articles from 2010 to 2023, adhering to PRISMA guidelines. Among 457 studies, seven met eligibility criteria, employing surveys and national database analyses as prevalent methods. Current care standards involved albumin and terlipressin treatment, with continuous intravenous terlipressin administration proving equally effective and better-tolerated than boluses. Despite its 40-50% success rate, predictors included serum bilirubin and creatinine levels, blood pressure, and systemic inflammatory response syndrome presence. Liver transplant stands as the sole curative avenue, while alternative therapies like dopamine, noradrenaline, renal and liver replacement therapy, and transjugular intrahepatic portosystemic shunt are under evaluation. Ongoing research into advanced remedies is imperative, given current treatment limitations. Considerations such as antibiotic prophylaxis in severe cirrhosis with low protein ascitic fluid levels and volume expansion with albumin during spontaneous bacterial peritonitis and high-volume paracentesis further underscore the multifaceted approach required in managing HRS. This study advocates for continuous exploration of innovative therapies and emphasizes the pivotal role of liver transplant consideration for eligible patients.

Severe Mitral Stenosis Presenting as Chronic Liver Disease: A Rare Case Report

High Serum Ascites Albumin Gradient (SAAG) ascites in severe rheumatic mitral stenosis is very uncommon. Hereby, the authors present a similar case with this rare combination. The present case report describes a 42-year-old male with no history of hypertension or diabetes, but occasional alcohol consumption, who presented to department with complaints of recurrent anasarca over the past five years. The electrocardiogram showed an irregular R-R interval with no P waves, indicating atrial fibrillation. Ascitic fluid analysis revealed a high serum ascites albumin gradient with low ascitic protein levels. The patient responded well to treatment and was discharged with appropriate medications. He was referred to a higher centre with cardiothoracic surgical facilities for mitral valve replacement and tricuspid annuloplasty. The present case report highlights the uniqueness of the combination of severe rheumatic mitral stenosis and ascites.

Diagnostic Value of Ascitic Fluid Cholesterol Level in Differentiating Malignant Ascites from Non-Malignant Ascites

Background: Ascites, the accumulation of fluid in the peritoneal cavity, poses significant diagnostic challenges, particularly in differentiating between malignancy-related ascites (MRA) and non-malignant ascites (NMA). This differentiation is critical for appropriate clinical management. Objective: The study aimed to evaluate the diagnostic value of ascitic fluid cholesterol levels in distinguishing MRA from NMA. Methods: This cross-sectional study enrolled 48 patients with ascites, divided equally into Group A (MRA) and Group B (NMA). Diagnostic paracentesis was performed, and 20 ml of ascitic fluid was collected for analysis. Cholesterol levels were measured using the Zaks method. Demographic data were recorded, and statistical analysis was conducted using the Mann-Whitney U-test, with a p-value of 0.05 set for statistical significance. Results: Both groups had an equal gender distribution (12 males and 12 females in each), and the mean ages were 60.3 ± 19.1 years for Group A and 60.8 ± 17.9 years for Group B. The mean cholesterol level in ascitic fluid was significantly higher in Group B (189.9 ± 29.9 mg%) compared to Group A (167.73 ± 26.87 mg%), with mean standard deviations of 91.8 ± 12.4 and 20.4 ± 9.1, respectively. The p-values for gender distribution and age differences were &lt;0.001. Conclusion: The study demonstrated that cholesterol levels in ascitic fluid are a reliable biomarker for differentiating between MRA and NMA. Higher cholesterol levels were associated with non-malignant cases, offering a non-invasive, cost-effective diagnostic tool in clinical settings.

Investigation of Endotoxin Positivity in Ascites at the Time of Cell-free and Concentrated Ascites Re-infusion Therapy.

Objective The presence of endotoxin (ET) in ascites at the time of cell-free and concentrated ascites reinfusion therapy (CART) is generally assessed in patients with infectious disease status, but the exact rate of ET positivity in ascites for patients treated with CART is unknown. Methods We evaluated ET levels in ascites at the time of CART, regardless of the presence of infectious symptoms. The analysis was performed for 529 cases in 183 patients in whom ET levels in ascites were measured at 2 time points (pre- and post-processing). Results ET in ascites was positive in 8 of 529 cases. In the positive cases, the ET level after CART was significantly decreased. ET-positive patients had a significantly higher white blood cell count, neutrophil count, and serum CRP level before CART than ET-negative patients. Conclusion Collectively, our data suggest that ET may be present in ascites, regardless of the infectious symptoms, especially in patients with a high white blood cell count, neutrophil count, and serum CRP level. Although the ET level in the re-infusion ascites seems to be decreased by CART, the possibility of endotoxemia after CART should be considered for such patients.

Mechanism of ozone alleviation of malignant ascites in hepatocellular carcinoma through the inhibition of neutrophil extracellular traps.

Malignant ascites in hepatocellular carcinoma is usually a sign of advanced disease and poor prognosis and is also thought to be associated with chronic inflammation mediated by neutrophil extracellular trap (NET) networks. Although ozone, a strong oxidant, has significant antibacterial and anti-inflammatory effects, its effectiveness in treating malignant liver ascites is unclear. We first measured the levels of NETs in the peripheral blood of patients with liver cancer and healthy individuals. Next, we constructed the H22 tumor-bearing mouse model and observed the abdominal girth, body weight, survival rate, and survival time in each group; we marked the proteins associated with NETs in mouse intestinal tissues by immunofluorescence; cf-DNA and cytokines in ascites such as: tumor necrosis factor alpha (TNF-α), vascular endothelial growth factor (VEGF), interleukin 6 (IL-6), matrix metalloprotein 9 (MMP-9), and interferon gamma (IFN-γ) levels in ascites were measured by enzyme-linked immunosorbent assay. The expression levels of phosphorylated adenylate-activated protein kinase (P-AMPK) and scavenger receptor-A (SR-A) were detected by immunocytochemistry in the intestinal tissues of each group of mice. We further examined the expression of P-AMPK and SR-A proteins in ascites deposits by Western blotting. The results show, the plasma levels of NETs were higher in patients with hepatocellular carcinoma than in normal subjects (P < 0.01). Abdominal girth and body weight were significantly reduced in the ozone-treated group compared with the model group, while survival and survival time were dose dependently increased (both P < 0.05). NET-associated guanine histone H3 and myeloperoxidase were abundantly expressed at neutrophil aggregates in the intestinal tissues of the model mice, whereas their expression was significantly reduced in the ozone-treated group. The levels of cf-DNA, IL-6, IFN-γ, MMP-9, VEGF, and TNF-α were dose dependently increased in the ascites of H22 tumor-bearing mice in the ozone-treated group compared with the model group (all P < 0.01), while the expression of P-AMPK and SR-A proteins was increased in the ozone-treated group compared with the model group. Ozone showed significant antiperitoneal fluid production properties in H22 tumor-bearing mice, and ozone reduced peritoneal fluid production by activating AMPK and up-regulating SR-A phagocytosis damage-associated molecular patterns to reduce the production of NETs. This suggests that ozone could be used as a new drug for the treatment of malignant ascites in hepatocellular carcinoma.

Diagnostic Value of Ascitic Endocan Levels in the Diagnosis of the Spontaneous Bacterial Peritonitis

Abstract Background Spontaneous bacterial peritonitis (SBP) is a serious complication of liver cirrhosis and is defined as infected ascites in the absence of any recognizable secondary cause of infection. One of the possible mechanisms of developing Spontaneous bacterial peritonitis is bacterial translocation. Aim of the Work The aim of this study is to assess the role of ascitic endocan levels in the diagnosis of SBP in decompensated cirrhosis. Patients and Methods 90 cirrhotic patients with ascites were included in the current study and divided into 2 groups: SBP group with positive ascites culture or with an AF PMNL count ≥ 250/mm3 included 45 subjects. Non SBP group with negative ascites culture or with an AF PMNL count &amp;gt; 250/mm3 included 45 subjects. In the SBP group, the mean age was 58.77 years with male predominance (68.8%).As regard to Non SBP group, the mean age was 59.31 years with male predominance 57.8%. Results There was a statistical significant difference in between SBP group and Non-SBP group as regard to Platelets, ALT, ascetic Total leucocyte count, Protein and LDH. The most common presentation in SBP group was Upper GIT bleeding and Abdominal pain and the most common organism detected in the culture of ascitic fluid Escherichia coli (80%) followed by Streptococcus viridans (15.5%). Ascitic Endocan level was significantly higher in SBP group than Non-SBP group with P &amp;lt; 0.001. The sensitivity and specificity of Ascitic Endocan in detection of SBP were 84.85% and 82.69% respectively. There was a positive significant correlation in between Ascitic Endocan level and ALT, AST, bilirubin, CRP, Child class, MELD score, Blood Leukocytes and TLC (cell/mm3) in ascitic fluid in SBP group. The significant predictors of bad outcome in patients with SBP were higher ascitic fluid Endocan level, CRP and higher Glucose in ascitic fluid (mg/dl) levels Conclusion High Ascitic endocan level is common in cirrhotic patients with SBP than in Non-SBP and that means Ascitic endocan is related to the severity of the disease. Ascitic endocan level is an independent risk factor for SBP. High Ascitic endocan level is a significant predictor of bad outcome in patients with SBP. Therefore, measurement of Ascitic endocan level provide a new strategy to more aggressive treatments for high-risk groups. Ascitic endocan level could be used as an inflammatory biomarker for the prognosis of patients with SBP

A marked elevation in serum creatinine/cystatin C ratio may indicate pseudo-acute kidney injury due to urinary ascites: a case report and literature review

BackgroundUrinary ascites represents a scarcely observed pseudo-acute kidney injury in clinical settings. Protracted or missed diagnosis may hold grave ramifications for patient outcomes.Case presentationWe reported a case involving an elderly female patient experiencing pseudo-acute kidney injury accompanied by ascites, wherein her renal dysfunction persisted despite medical intervention and hemodialysis. Urinary ascites was identified via a methylene blue test and by contrasting creatinine levels in serum and ascites. This patient’s kidney function was multiple typified by a marked elevation in serum creatinine/Cystatin C ratio (> 2 L/dL), potentially serving as a clue for the clinical diagnosis of pseudo-acute kidney injury engendered by urinary ascites.ConclusionsThis case suggested the potential diagnostic value of an asynchronous increase in serum creatinine and serum CysC (or an increased ratio of blood creatinine to blood CysC) in patients with pseudo-acute kidney injury.

Liver Transplantation for Porto-sinusoidal Vascular Liver Disorder: Unmet Questions.

We read with great interest a recent international multicenter study by Marta Magaz et al,1 analyzing post-deceased donor liver transplantation outcomes in 50 of 587 porto-sinusoidal vascular disorder (PSVD) patients registered at 28 participating centers from 1990 to 2020. Additionally, 4 of the 28 centers, performing 4322 LTs, reclassified 29 patients as PSVD after reviewing explant histology registries. We have specific essential points to note. First, the risk of progression of PSVD to advanced liver disease is highly variable, but the specific risk factors and the pathogenic mechanisms leading to these complications should have been researched. Given that the diagnosis of PSVD primarily relied on the recognition of “specific” histologic features on good-quality liver biopsies before liver transplantation (LT),2 the histological changes in the 50 explant livers should have been studied and compared with pre-LT liver biopsies to grade the severity of lesions. Theoretically, it makes sense that the degree of histological changes corresponds to the degree of portal hypertension (PHT) and decompensation. Currently, the individual histologic lesions of PSVD are evaluated using a 2-tiered system for the lesion’s absence (score 0) or presence (score 1). In the presence of similar histological lesions, it is imperative to know why some patients with PSVD developed portal hypertension and decompensation, and others did not. Vice versa, does the grading of histological lesions differ for PSVD patients who develop severe PHT and decompensation compared with those who do not? Maybe the authors can study the 50 explants with this perspective and pick up the other subtle differences between decompensated PSVD versus cirrhosis patients. Second, with PSVD being a presinusoidal disorder, probably a higher portal pressure may be required to produce a similar level of ascites than in patients with cirrhosis. Also, PSVD patients commonly have sinusoidal dilation as a finding in liver samples. Hence, it is important to know if the hepatic venous pressure gradient measurement has been done in these 50 decompensated PSVD patients to identify the presence of sinusoidal PHT.3,4 Third, LT was indicated for 2 of 79 PSVD patients with hepatocellular carcinoma. One had a history of previous hepatitis B with negative HBsAg and undetectable DNA before LT. The other patient had type 2 diabetes and showed obliterative portal venopathy and incomplete septal fibrosis. In patients with hepatocellular carcinoma (HCC), it is imperative to consider the possibility of a coexisting second potential trigger of HCC as PSVD is infrequently associated with HCC,5 and the exact etiopathogenesis of HCC in the setting of PSVD is unclear. Also, incomplete septal cirrhosis may represent regressed cirrhosis and may be unrelated to the risk factors of PSVD.6 In this case, let us assume an overlap of PSVD and parenchymal liver disease, but how to determine the respective contribution of each in the development of HCC is unclear. Hence, these 2 HCC patients may not have been included in the study. Fourth, 21 PSVD patients with severe associated conditions had suboptimal 1-y (85.2 versus 74.3%) and 5-y survival (74.8 versus 45.3%). In the deceased donor liver transplantation setting, the principle of nonfutility is also as important as the principle of utility.7 Hence, organ allocation to these patients should be critically appraised.

(-)-Epigallocatechin-3-Gallate Attenuates the Adverse Reactions Triggered by Selenium Nanoparticles without Compromising Their Suppressing Effect on Peritoneal Carcinomatosis in Mice Bearing Hepatocarcinoma 22 Cells.

Increasing evidence shows that selenium and polyphenols are two types of the most reported compounds in tumor chemoprevention due to their remarkable antitumor activity and high safety profile. The cross-talk between polyphenols and selenium is a hot research topic, and the combination of polyphenols and selenium is a valuable strategy for fighting cancer. The current work investigated the combination anti-peritoneal carcinomatosis (PC) effect of selenium nanoparticles (SeNPs) and green tea (Camellia sinensis) polyphenol (-)-epigallocatechin-3-gallate (EGCG) in mice bearing murine hepatocarcinoma 22 (H22) cells. Results showed that SeNPs alone significantly inhibited cancer cell proliferation and extended the survival time of mice bearing H22 cells. Still, the potential therapeutic efficacy is accompanied by an approximately eighty percent diarrhea rate. When EGCG was combined with SeNPs, EGCG did not affect the tumor proliferation inhibition effect but eliminated diarrhea triggered by SeNPs. In addition, both the intracellular selectively accumulated EGCG without killing effect on cancer cells and the enhanced antioxidant enzyme levels in ascites after EGCG was delivered alone by intraperitoneal injection indicated that H22 cells were insensitive to EGCG. Moreover, EGCG could prevent SeNP-caused systemic oxidative damage by enhancing serum superoxide dismutase, glutathione, and glutathione peroxidase levels in healthy mice. Overall, we found that H22 cells are insensitive to EGCG, but combining EGCG with SeNPs could protect against SeNP-triggered diarrhea without compromising the suppressing efficacy of SeNPs on PC in mice bearing H22 cells and attenuate SeNP-caused systemic toxicity in healthy mice. These results suggest that EGCG could be employed as a promising candidate for preventing the adverse reactions of chemotherapy including chemotherapy-induced diarrhea and systemic toxicity in cancer individuals.

A multicenter retrospective cohort study evaluating the clinical significance of CA125 in later line of patients with metastatic colorectal cancer.

253 Background: The peritoneal dissemination is one of the metastatic forms of gastrointestinal cancer and has a poor prognosis. It has been reported that the presence of CA125 in mesothelial cells lining the peritoneum is involved in the elevation of CA125 due to peritoneal dissemination and inflammation of cancerous ascites, and CA125 may be a useful predictor of peritoneal dissemination in gastrointestinal cancer. It has also been reported that CA125 correlates with ascites volume and prognosis. However, there are no reports evaluating the clinical significance of CA125 in the later line of metastatic colorectal cancer (mCRC). Therefore, we conducted a multicenter retrospective study. Methods: We retrospectively analyzed the clinical data of 121 patients who received trifluridine/tipiracil (FTD/TPI) or Regorafenib from January 2012 to May 2018 in 10 centers and had the result of serum CA125 just before the treatment. Patients who had received either FTD/TPI or Regorafenib were excluded. In this study, the levels of ascites were classified as follows: "none" as undetectable by computed tomography scanning, "mild" as confined to the pelvic cavity or upper abdomen, "severe" as continuous from the pelvic cavity to the upper abdomen, and "moderate" as between "mild" and "severe". RECIST ver.1.1 was used for analysis of tumor response. Survival analyses were performed with Kaplan-Meier method, log-rank test and Cox proportional hazards model. Results: There were 75 patients in the baseline CA125 normal group (group N) and 46 patients in the high group (group H). ECOG PS tended to be worse in group H than in group N (ECOG PS (0/1/2) 26/43/6 and 9/28/9 in N and H groups, p=0.076). There were significantly more patients with ascites in group H than in group N (Yes/No 7/68 and 26/20 in N and H groups, p&lt;0.001). Furthermore, ALP, CRP, CA19-9 and NLR were significantly higher, and Alb was significantly lower in group H than in group N. Baseline CA125 correlated with baseline ascites volume (p&lt;0.001). PFS and OS were significantly shorter in group H compared to group N (PFS; 1.9 vs. 3.0 months; HR 1.576 [95%CI 1.081-2.299]; p=0.016, OS; 4.1 vs. 11.0 months; HR 2.418 [95%CI 1.634-3.576]; p&lt;0.001). The rate of change for CA125 was significantly higher in patients with progressive disease on first evaluation CT compared to patients with disease control (p=0.002), and PFS and OS were significantly shorter in the increased CA125 group measured first after treatment than in the non-increased CA125 group (PFS; 1.9 vs. 4.6 months; HR 3.104 [95%CI, 2.004-4.809]; p&lt;0.001, OS; 5.9 vs. 13.0 months; HR 2.199 [95%CI, 1.474-3.282]; p&lt;0.001). Conclusions: In this retrospective analysis, baseline CA125 correlated with ascites volume in later line treatment of patients with mCRC, suggesting that increased CA125 may be a predictive and prognostic factor. Clinical trial information: UMIN000040059 .