-
Nature Cancer Aug 2023Ovarian cancer (OC) is an aggressive gynecological tumor usually diagnosed with widespread metastases and ascites. Here, we depicted a single-cell landscape of the OC...
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.
Topics: Female; Humans; Ascites; CD8-Positive T-Lymphocytes; Ecosystem; Ovarian Neoplasms; Single-Cell Analysis
PubMed: 37488416
DOI: 10.1038/s43018-023-00599-8 -
Biochimica Et Biophysica Acta. Reviews... Sep 2023Ovarian cancer (OVCA) is the second most common gynecological cancer and one of the leading causes of cancer related mortality among women. Recent studies suggest that... (Review)
Review
Ovarian cancer (OVCA) is the second most common gynecological cancer and one of the leading causes of cancer related mortality among women. Recent studies suggest that among ovarian cancer patients at least 70% of the cases experience the involvement of lymph nodes and metastases through lymphatic vascular network. However, the impact of lymphatic system in the growth, spread and the evolution of ovarian cancer, its contribution towards the landscape of ovarian tissue resident immune cells and their metabolic responses is still a major knowledge gap. In this review first we present the epidemiological aspect of the OVCA, the lymphatic architecture of the ovary, we discuss the role of lymphatic circulation in regulation of ovarian tumor microenvironment, metabolic basis of the upregulation of lymphangiogenesis which is often observed during progression of ovarian metastasis and ascites development. Further we describe the implication of several mediators which influence both lymphatic vasculature as well as ovarian tumor microenvironment and conclude with several therapeutic strategies for targeting lymphatic vasculature in ovarian cancer progression in present day.
Topics: Humans; Female; Lymphatic Vessels; Ovarian Neoplasms; Lymphangiogenesis; Lymph Nodes; Tumor Microenvironment
PubMed: 37419192
DOI: 10.1016/j.bbcan.2023.188950 -
Praxis Sep 2023Cirrhosis is a common disease with high morbidity and mortality. In industrialised countries, the most common causes of cirrhosis are the alcoholic liver disease,...
Cirrhosis is a common disease with high morbidity and mortality. In industrialised countries, the most common causes of cirrhosis are the alcoholic liver disease, non-alcoholic fatty liver disease and chronic viral hepatitis. Cirrhosis is often diagnosed late, as it can be asymptomatic for a long time. Therefore, hepatopathy screening in high-risk patients and fibrosis surveillance using the ultrasound, in the presence of a chronic hepatopathy are essential. A liver biopsy is necessary to confirm the diagnosis. With optimal therapy, in some cases, cirrhosis is preventable and potentially reversible in others. In the stage of decompensation, typically characterised by ascites, patients often die from recurrent infections or hepatocellular carcinoma unless cured by liver transplantation. The prevention and treatment of complications as well as the evaluation of a transplant require cooperation with a centre hospital.
Topics: Humans; Liver Cirrhosis; Carcinoma, Hepatocellular; Non-alcoholic Fatty Liver Disease; Liver Transplantation; Liver Neoplasms
PubMed: 37823811
DOI: No ID Found -
JAMA Apr 2024Metabolic dysfunction-associated steatotic liver disease (MASLD) is currently the most common chronic liver disease worldwide. It is important to develop noninvasive...
IMPORTANCE
Metabolic dysfunction-associated steatotic liver disease (MASLD) is currently the most common chronic liver disease worldwide. It is important to develop noninvasive tests to assess the disease severity and prognosis.
OBJECTIVE
To study the prognostic implications of baseline levels and dynamic changes of the vibration-controlled transient elastography (VCTE)-based scores developed for the diagnosis of advanced fibrosis (Agile 3+) and cirrhosis (Agile 4) in patients with MASLD.
DESIGN, SETTING, AND PARTICIPANTS
This cohort study included data from a natural history cohort of patients with MASLD who underwent VCTE examination at 16 tertiary referral centers in the US, Europe, and Asia from February 2004 to January 2023, of which the data were collected prospectively at 14 centers. Eligible patients were adults aged at least 18 years with hepatic steatosis diagnosed by histologic methods (steatosis in ≥5% of hepatocytes) or imaging studies (ultrasonography, computed tomography or magnetic resonance imaging, or controlled attenuation parameter ≥248 dB/m by VCTE).
MAIN OUTCOMES AND MEASURES
The primary outcome was liver-related events (LREs), defined as hepatocellular carcinoma or hepatic decompensation (ascites, variceal hemorrhage, hepatic encephalopathy, or hepatorenal syndrome), liver transplant, and liver-related deaths. The Agile scores were compared with histologic and 8 other noninvasive tests.
RESULTS
A total of 16 603 patients underwent VCTE examination at baseline (mean [SD] age, 52.5 [13.7] years; 9600 [57.8%] were male). At a median follow-up of 51.7 (IQR, 25.2-85.2) months, 316 patients (1.9%) developed LREs. Both Agile 3+ and Agile 4 scores classified fewer patients between the low and high cutoffs than most fibrosis scores and achieved the highest discriminatory power in predicting LREs (integrated area under the time-dependent receiver-operating characteristic curve, 0.89). A total of 10 920 patients (65.8%) had repeated VCTE examination at a median interval of 15 (IQR, 11.3-27.7) months and were included in the serial analysis. A total of 81.9% of patients (7208 of 8810) had stable Agile 3+ scores and 92.6% of patients (8163 of 8810) had stable Agile 4 scores (same risk categories at both assessments). The incidence of LREs was 0.6 per 1000 person-years in patients with persistently low Agile 3+ scores and 30.1 per 1000 person-years in patients with persistently high Agile 3+ scores. In patients with high Agile 3+ score at baseline, a decrease in the score by more than 20% was associated with substantial reduction in the risk of LREs. A similar trend was observed for the Agile 4 score, although it missed more LREs in the low-risk group.
CONCLUSIONS AND RELEVANCE
Findings of this study suggest that single or serial Agile scores are highly accurate in predicting LREs in patients with MASLD, making them suitable alternatives to liver biopsy in routine clinical practice and in phase 2b and 3 clinical trials for steatohepatitis.
Topics: Adult; Humans; Male; Adolescent; Middle Aged; Female; Elasticity Imaging Techniques; Cohort Studies; Vibration; Esophageal and Gastric Varices; Gastrointestinal Hemorrhage; Liver; Liver Cirrhosis; Fatty Liver; Carcinoma, Hepatocellular; Liver Neoplasms
PubMed: 38512249
DOI: 10.1001/jama.2024.1447 -
Anticancer Research Feb 2024Malignant ascites is a common condition in patients with terminal cancer. Treatments, such as diuretics, percutaneous drainage of ascites, and abdominal vein shunting... (Observational Study)
Observational Study
BACKGROUND/AIM
Malignant ascites is a common condition in patients with terminal cancer. Treatments, such as diuretics, percutaneous drainage of ascites, and abdominal vein shunting have been advocated. However, these treatments have not achieved sufficient palliative effects. Therefore, the development of innovative therapies is mandated, especially for new therapies that require the creation of a fluid simulation of malignant ascites. However, there have been no previous studies on the physical properties of malignant ascites, including viscosity, which are necessary for the development of such a fluid. Therefore, we prospectively investigated the physical properties of malignant ascites.
PATIENTS AND METHODS
This single-center, prospective, observational study included 30 patients between November 2021 and January 2023. The primary endpoint was the viscosity of the malignant ascites, and the secondary endpoints included other viscosity studies, biochemical tests, and the presence of malignant cells in the ascites.
RESULTS
The median viscosity was 1.105 mPa*S. The viscosity of malignant ascites tended to decrease with increasing temperature, which is common for liquids. Malignant ascites fluid containing malignant cells tended to be more viscous than ascites fluid without malignant cells; furthermore, albumin levels tended to be higher in the former than in the latter.
CONCLUSION
Malignant ascites' median viscosity was 1.105 mPa*S. Correlation between viscosity and temperature showed a decreasing trend. These findings contribute valuable insights for future malignant ascites management and device development.
Topics: Humans; Ascites; Prospective Studies; Viscosity; Ascitic Fluid; Peritoneal Neoplasms
PubMed: 38307583
DOI: 10.21873/anticanres.16841 -
The Lancet. Gastroenterology &... Sep 2023Data are scarce regarding the development of hepatic decompensation in patients with non-alcoholic fatty liver disease (NAFLD) with and without type 2 diabetes. We aimed... (Meta-Analysis)
Meta-Analysis
Type 2 diabetes, hepatic decompensation, and hepatocellular carcinoma in patients with non-alcoholic fatty liver disease: an individual participant-level data meta-analysis.
BACKGROUND
Data are scarce regarding the development of hepatic decompensation in patients with non-alcoholic fatty liver disease (NAFLD) with and without type 2 diabetes. We aimed to assess the risk of hepatic decompensation in people with NAFLD with and without type 2 diabetes.
METHODS
We did a meta-analysis of individual participant-level data from six cohorts in the USA, Japan, and Turkey. Included participants had magnetic resonance elastography between Feb 27, 2007, and June 4, 2021. Eligible studies included those with liver fibrosis characterisation by magnetic resonance elastography, longitudinal assessment for hepatic decompensation and death, and included adult patients (aged ≥18 years) with NAFLD, for whom data were available regarding the presence of type 2 diabetes at baseline. The primary outcome was hepatic decompensation, defined as ascites, hepatic encephalopathy, or variceal bleeding. The secondary outcome was the development of hepatocellular carcinoma. We used competing risk regression using the Fine and Gray subdistribution hazard ratio (sHR) to compare the likelihood of hepatic decompensation in participants with and without type 2 diabetes. Death without hepatic decompensation was a competing event.
FINDINGS
Data for 2016 participants (736 with type 2 diabetes; 1280 without type 2 diabetes) from six cohorts were included in this analysis. 1074 (53%) of 2016 participants were female with a mean age of 57·8 years (SD 14·2) years and BMI of 31·3 kg/m (SD 7·4). Among 1737 participants (602 with type 2 diabetes and 1135 without type 2 diabetes) with available longitudinal data, 105 participants developed hepatic decompensation over a median follow-up time of 2·8 years (IQR 1·4-5·5). Participants with type 2 diabetes had a significantly higher risk of hepatic decompensation at 1 year (3·37% [95% CI 2·10-5·11] vs 1·07% [0·57-1·86]), 3 years (7·49% [5·36-10·08] vs 2·92% [1·92-4·25]), and 5 years (13·85% [10·43-17·75] vs 3·95% [2·67-5·60]) than participants without type 2 diabetes (p<0·0001). After adjustment for multiple confounders (age, BMI, and race), type 2 diabetes (sHR 2·15 [95% CI 1·39-3·34]; p=0·0006) and glycated haemoglobin (1·31 [95% CI 1·10-1·55]; p=0·0019) were independent predictors of hepatic decompensation. The association between type 2 diabetes and hepatic decompensation remained consistent after adjustment for baseline liver stiffness determined by magnetic resonance elastography. Over a median follow-up of 2·9 years (IQR 1·4-5·7), 22 of 1802 participants analysed (18 of 639 with type 2 diabetes and four of 1163 without type 2 diabetes) developed incident hepatocellular carcinoma. The risk of incident hepatocellular carcinoma was higher in those with type 2 diabetes at 1 year (1·34% [95% CI 0·64-2·54] vs 0·09% [0·01-0·50], 3 years (2·44% [1·36-4·05] vs 0·21% [0·04-0·73]), and 5 years (3·68% [2·18-5·77] vs 0·44% [0·11-1·33]) than in those without type 2 diabetes (p<0·0001). Type 2 diabetes was an independent predictor of hepatocellular carcinoma development (sHR 5·34 [1·67-17·09]; p=0·0048).
INTERPRETATION
Among people with NAFLD, the presence of type 2 diabetes is associated with a significantly higher risk of hepatic decompensation and hepatocellular carcinoma.
FUNDING
National Institute of Diabetes and Digestive and Kidney Diseases.
Topics: Adult; Humans; Female; Adolescent; Middle Aged; Male; Carcinoma, Hepatocellular; Non-alcoholic Fatty Liver Disease; Diabetes Mellitus, Type 2; Liver Neoplasms; Esophageal and Gastric Varices; Gastrointestinal Hemorrhage
PubMed: 37419133
DOI: 10.1016/S2468-1253(23)00157-7 -
The Journal of the Royal College of... Sep 2023
Topics: Humans; Pseudomyxoma Peritonei; Peritoneal Neoplasms
PubMed: 37329264
DOI: 10.1177/14782715231179254 -
Journal of Cachexia, Sarcopenia and... Oct 2023Malignant ascites is prevalent in advanced-stage ovarian cancer and may facilitate identification of the drivers of muscle loss. This study aimed to evaluate the...
BACKGROUND
Malignant ascites is prevalent in advanced-stage ovarian cancer and may facilitate identification of the drivers of muscle loss. This study aimed to evaluate the association of ascites with changes in systemic inflammation and muscle after treatment of advanced-stage ovarian cancer.
METHODS
We evaluated 307 patients with advanced-stage (III/IVA) ovarian cancer who underwent primary debulking surgery and adjuvant platinum-based chemotherapy between 2010 and 2019. The changes in skeletal muscle index (SMI) and radiodensity (SMD) were measured using pre-surgery and post-chemotherapy portal-venous phase contrast-enhanced computed tomography scans at L3. Systemic inflammation was measured using albumin levels, prognostic nutritional index (PNI), neutrophil-lymphocyte ratio (NLR), and platelet-lymphocyte ratio (PLR). Primary endpoint was the changes in SMI and SMD after treatment. Linear regression analysis was used to test associations between muscle change and other covariates. Mediation analysis was used to determine the mediator.
RESULTS
The median (range) age was 53 (23-83) years. The median duration (range) of follow-up was 5.2 (1.1-11.3) years. Overall, 187 (60.9%) patients had ascites. The changes in muscle and systemic inflammatory markers after treatment were significantly different between patients with and without ascites (SMI: -3.9% vs. 2.2%, P < 0.001; SMD: -4.0% vs. -0.4%, P < 0.001; albumin: -4.4% vs. 2.1%, P < 0.001; PNI: -8.4% vs. -0.1%, P < 0.001; NLR: 20.6% vs. -29.4%, P < 0.001; and PLR: 1.7% vs. -19.4%, P < 0.001). The changes in SMI and SMD were correlated with the changes in albumin, PNI, NLR, and PLR (all P < 0.001). In multiple linear regression, ascites and NLR changes were negatively while albumin change was positively correlated with SMI change (ascites: β = -3.19, P < 0.001; NLR change: β = -0.02, P = 0.003; albumin change: β = 0.37, P < 0.001). Ascites and NLR changes were negatively while PNI change was positively correlated with SMD change (ascites: β = -1.28, P = 0.02; NLR change: β = -0.02, P < 0.001; PNI change: β = 0.11, P = 0.04). In mediation analysis, ascites had a direct effect on SMI change (P < 0.001) and an indirect effect mediated by NLR change (indirect effects = -1.61, 95% confidence interval [CI]: -2.22 to -1.08) and albumin change (indirect effects = -2.92, 95% CI: -4.01 to -1.94). Ascites had a direct effect on SMD change (P < 0.001) and an indirect effect mediated by NLR change (indirect effects = -1.76, 95% CI: -2.34 to -1.22) and PNI change (indirect effects = -2.00, 95% CI: -2.79 to -1.36).
CONCLUSIONS
Malignant ascites was associated with enhanced systemic inflammation and muscle loss after primary debulking surgery and adjuvant chemotherapy in advanced-stage ovarian cancer. The association between ascites and muscle loss may be mediated by systemic inflammation.
Topics: Humans; Female; Middle Aged; Aged; Aged, 80 and over; Prognosis; Ascites; Inflammation; Muscle, Skeletal; Ovarian Neoplasms; Albumins
PubMed: 37503876
DOI: 10.1002/jcsm.13289