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Alimentary Pharmacology & Therapeutics May 2022Cirrhosis is increasingly common and morbid. Optimal utilisation of therapeutic strategies to prevent and control the complications of cirrhosis are central to improving... (Review)
Review
BACKGROUND
Cirrhosis is increasingly common and morbid. Optimal utilisation of therapeutic strategies to prevent and control the complications of cirrhosis are central to improving clinical and patient-reported outcomes.
METHODS
We conducted a narrative review of the literature focusing on the most recent advances.
RESULTS
We review the aetiology-focused therapies that can prevent cirrhosis and its complications. These include anti-viral therapies, psychopharmacological therapy for alcohol-use disorder, and the current landscape of clinical trials for non-alcoholic steatohepatitis. We review the current standard of care and latest developments in the management of hepatic encephalopathy (HE), ascites and hepatorenal syndrome. We evaluate the promise and drawbacks of chemopreventative therapies that have been examined in trials and observational studies which may reduce the risk of hepatocellular carcinoma and cirrhosis complications. Finally, we examine the therapies which address the non-pain symptoms of cirrhosis including pruritis, muscle cramps, sexual dysfunction and fatigue.
CONCLUSION
The improvement of clinical and patient-reported outcomes for patients with cirrhosis is possible by applying evidence-based pharmacotherapeutic approaches to the prevention and treatment of cirrhosis complications.
Topics: Ascites; Esophageal and Gastric Varices; Female; Hepatic Encephalopathy; Humans; Liver Cirrhosis; Liver Neoplasms; Male
PubMed: 35235219
DOI: 10.1111/apt.16831 -
International Journal of Cancer Oct 2020Malignant ascites is one of the major clinical features of ovarian cancer, which serves as a carrier for the peritoneal dissemination of tumor cells and predicts a poor... (Review)
Review
Malignant ascites is one of the major clinical features of ovarian cancer, which serves as a carrier for the peritoneal dissemination of tumor cells and predicts a poor prognosis in patients. In the microenvironment of ovarian cancer ascites, antitumor immunity is suppressed, which enables the tumor cells to escape from immune surveillance. The metabolic factors, including hypoxia, nutrient deprivation and accumulation of metabolic products, contribute to the immunosuppressive status of malignant ascites. The malignant ascites and ovarian solid tumors exhibit differential metabolic profiles. In this review, we have summarized the most recent findings on the interaction between immune cells and metabolic factors in the ovarian cancer ascites. The effects of metabolic factors on the antitumor functions of T-cells in the malignant ascites were analyzed. Finally, we have discussed the potential directions for future research in this field.
Topics: Ascites; Female; Humans; Neoplasm Grading; Ovarian Neoplasms; T-Lymphocytes; Tumor Escape; Tumor Hypoxia; Tumor Microenvironment
PubMed: 32208517
DOI: 10.1002/ijc.32990 -
Seminars in Cancer Biology Nov 2022The ascites ecosystem in ovarian cancer is inhabited by complex cell types and is bathed in an environment rich in cytokines, chemokines, and growth factors that... (Review)
Review
The ascites ecosystem in ovarian cancer is inhabited by complex cell types and is bathed in an environment rich in cytokines, chemokines, and growth factors that directly and indirectly impact metabolism of cancer cells and tumor associated cells. This milieu of malignant ascites, provides a 'rich' environment for the disease to thrive, contributing to every aspect of advanced ovarian cancer, a devastating gynecological cancer with a significant gap in targeted therapeutics. In this perspective we focus our discussions on the 'acellular' constituents of this liquid malignant tumor microenvironment, and how they influence metabolic pathways. Growth factors, chemokines and cytokines are known modulators of metabolism and have been shown to impact nutrient uptake and metabolic flexibility of tumors, yet few studies have explored how their enrichment in malignant ascites of ovarian cancer patients contributes to the metabolic requirements of ascites-resident cells. We focus here on TGF-βs, VEGF and ILs, which are frequently elevated in ovarian cancer ascites and have all been described to have direct or indirect effects on metabolism, often through gene regulation of metabolic enzymes. We summarize what is known, describe gaps in knowledge, and provide examples from other tumor types to infer potential unexplored roles and mechanisms for ovarian cancer. The distribution and variation in acellular ascites components between patients poses both a challenge and opportunity to further understand how the ascites may contribute to disease heterogeneity. The review also highlights opportunities for studies on ascites-derived factors in regulating the ascites metabolic environment that could act as a unique signature in aiding clinical decisions in the future.
Topics: Female; Humans; Ascites; Ecosystem; Carcinoma, Ovarian Epithelial; Ovarian Neoplasms; Intercellular Signaling Peptides and Proteins; Cytokines; Tumor Microenvironment
PubMed: 35259492
DOI: 10.1016/j.semcancer.2022.03.004 -
Journal of Cancer Research and Clinical... Nov 2019Malignant ascites (MA) is a common manifestation in advanced gastric cancer with peritoneal carcinomatosis and usually indicates a poor prognosis. However, lack of in...
PURPOSE
Malignant ascites (MA) is a common manifestation in advanced gastric cancer with peritoneal carcinomatosis and usually indicates a poor prognosis. However, lack of in vitro models that can faithfully recapitulate the characteristics of tumour cells in ascites hinders related researches. Tumour organoids have emerged as a robust in vitro model for tumour research and drug screening. Hence, we aimed to generate a 3-D in vitro organoid cultures from malignant ascites of gastric cancer for disease modelling and drug screening.
METHODS
Eleven MADOs were generated from the MA tumour cells of gastric cancer patients. We made comparisons between MADOs and original MA tumour cells in histopathology by immunohistochemistry and genomics by whole-exome sequencing. In order to evaluate MADOs as functional in vitro disease models, we tested whether MADOs could be used for drug sensitivity screens.
RESULTS
Eleven MADO cultures from human gastric cancer were established. MADOs demonstrated divergent growth characteristics and morphologies. MADO cultures preserve the histological architecture, genomic landscape of the corresponding MA tumour cells. MADOs exhibited heterogeneous responses to standard-of-care chemotherapeutics.
CONCLUSIONS
We generated MADOs modelling characteristics and mutated genes of MA tumour cells. A broad range of intrinsic MADO response to conventional chemotherapeutics suggests MADOs are amenable to drug screening.
Topics: Antineoplastic Agents; Ascites; Cell Proliferation; Drug Screening Assays, Antitumor; Humans; In Vitro Techniques; Organ Culture Techniques; Organoids; Stomach Neoplasms; Tumor Cells, Cultured; Exome Sequencing
PubMed: 31598791
DOI: 10.1007/s00432-019-03004-z -
Journal of Palliative Medicine Jul 2022To compare outcomes of PleurX and peritoneal port for malignant ascites. Retrospective review of medical records was conducted. Subjects were consecutive patients...
To compare outcomes of PleurX and peritoneal port for malignant ascites. Retrospective review of medical records was conducted. Subjects were consecutive patients receiving PleurX or peritoneal port for malignant ascites in a center in Sydney, Australia. Demographic data, complication rates, hospitalization rates, and survival were measured. Sixteen cases were analyzed: 6 had peritoneal port (170 catheter days) and 10 had PleurX (477 catheter days). Complication rates were low with both drainage systems. Cellulitis rate was 33% (1.2 events/100 catheter days) for peritoneal port and 10% (0.2 events/100 catheter days) for PleurX. Hospital admission days were 27 days/100 catheter days for peritoneal port and 5.2 days/100 catheter days for PleurX. Both PleurX and peritoneal port seem feasible options in draining malignant ascites. Further research is needed to ascertain whether there are true differences in cellulitis/admission rates. Patient quality of life, experience, and preference should be included in future studies.
Topics: Ascites; Catheters, Indwelling; Cellulitis; Humans; Peritoneal Neoplasms; Quality of Life; Retrospective Studies
PubMed: 35333615
DOI: 10.1089/jpm.2021.0504 -
Molecular Therapy : the Journal of the... Jun 2024Malignant ascites is a common complication resulting from the peritoneal spread of malignancies, and currently lacks effective treatments. We conducted a phase II trial...
Malignant ascites is a common complication resulting from the peritoneal spread of malignancies, and currently lacks effective treatments. We conducted a phase II trial (NCT04771676) to investigate the efficacy and safety of oncolytic adenovirus H101 and virotherapy-induced immune response in 25 patients with malignant ascites. Oncolytic virotherapy achieved an increased median time to repeat paracentesis of 45 days (95% confidence interval 16.5-73.5 days), compared with the preset control value of 13 days. Therapy was well-tolerated, with pyrexia, fatigue, nausea, and abdominal pain as the most common toxicities. Longitudinal single-cell profiling identified marked oncolysis, early virus replication, and enhanced CD8 T cells-macrophages immune checkpoint crosstalk, especially in responsive patients. H101 also triggered a proliferative burst of CXCR6 and GZMKCD8 T cells with promoted tumor-specific cytotoxicity. Further establishment of oncolytic virus-induced T cell expansion signature (OiTE) implicated the potential benefits for H101-responsive patients from subsequent anti-PD(L)1 therapy. Patients with upregulated immune-signaling pathways in tumor cells and a higher proportion of CLEC10A dendritic cells and GZMKCD8 T cells at baseline showed a superior response to H101 treatment. Our study demonstrates promising clinical responses and tolerability of oncolytic adenovirus in treating malignant ascites and provides insights into the relevant cellular processes following oncolytic virotherapy.
Topics: Humans; Oncolytic Virotherapy; Oncolytic Viruses; Ascites; Female; Male; Middle Aged; Adenoviridae; Aged; Single-Cell Analysis; CD8-Positive T-Lymphocytes; Adult; Treatment Outcome; Longitudinal Studies; Virus Replication
PubMed: 38659226
DOI: 10.1016/j.ymthe.2024.04.029 -
The Journal of Obstetrics and... Apr 2021Ascites is a tumor microenvironment, ascites and massive ascites-induce compression could promote the progression of epithelial ovarian cancer (EOC); however, the impact...
OBJECTIVE
Ascites is a tumor microenvironment, ascites and massive ascites-induce compression could promote the progression of epithelial ovarian cancer (EOC); however, the impact of ascites volume on clinical outcomes has not been studied extensively. We aimed to investigate the association between ascites volume and clinical outcomes especially platinum resistance in EOC.
METHODS
We retrospectively evaluated a total of 546 EOC patients with respect to the amount of ascites, clinicopathologic factors, and survival. Using the threshold of 1500 ml to classify patients into small- and large-volume ascites groups, we analyzed the correlation between ascites volume and clinicopathological factors, including platinum-free interval (PFI), and prognosis.
RESULTS
Patients with large volume ascites were more likely to present with later stage disease, primary platinum-resistant (PPR) cancer, and suboptimal cytoreduction. Prolonged PFI was associated with decreased ascites volume. The large-volume ascites group showed worse progression-free survival (PFS) and overall survival (OS). An increase in ascites volume was associated with an increased risk of disease recurrence (hazard ratio [HR] = 1.115, 95% confidence interval [CI]: 1.035-1.200) and death (HR = 1.213, 95% CI: 1.090-1.350).
CONCLUSIONS
Ascites was an independent predictor of PFS and OS in EOC patients. A large volume of ascites predicated a shortened PFI, an increased incidence of PPR and suboptimal cytoreduction. Thus, the volume of ascites is a simply available clinical parameter, which could be used to evaluate the prognosis and platinum resistance of EOC patients early, it contributes to formulate individualized treatment plan and improve the outcome of EOC patients.
Topics: Ascites; Carcinoma, Ovarian Epithelial; Female; Humans; Neoplasm Recurrence, Local; Neoplasms, Glandular and Epithelial; Ovarian Neoplasms; Prognosis; Retrospective Studies; Tumor Microenvironment
PubMed: 33506580
DOI: 10.1111/jog.14682 -
Journal of Controlled Release :... Sep 2023Cytoreductive surgery (CRS) has emerged as a survival-extending treatment of peritoneal metastasis (PM); recent advances include using intraperitoneal chemotherapy (IPC)...
Cytoreductive surgery (CRS) has emerged as a survival-extending treatment of peritoneal metastasis (PM); recent advances include using intraperitoneal chemotherapy (IPC) at normothermic or hyperthermic temperatures, or under pressure (CRS + IPC). Clinical CRS + IPC research has established its highly variable efficacy and suggested tumor size, tumor locations and presence of ascites as potential determinants. On the other hand, there is limited knowledge on the effects of pharmaceutical properties on treatment outcomes. The present study investigated the inter-subject variability of paclitaxel binding to proteins in patient ascites because some PM patients show accumulation of ascites and because activity and transport of highly protein-bound drugs such as paclitaxel are affected by protein binding. Ascites samples were collected from 26 patients and investigated for their protein contents using LC/MS/MS proteomics analysis and for the concentrations of total proteins and two major paclitaxel-binding proteins (human serum albumin or HSA and α-1-acid glycoprotein or AAG). The association constants of paclitaxel to HSA and AAG and the extent of protein binding of paclitaxel in patient ascites were studied using equilibrium dialysis. Proteomic analysis of four randomly selected samples revealed 288 proteins, >90% of which are also present in human plasma. Between 72% - 94% of paclitaxel was bound to proteins in patient ascites. The concentrations of HSA and AAG in ascites showed substantial inter-subject variations, ranging from 14.7 - 46.3 mg/mL and 0.13-2.56 mg/mL, respectively. The respective paclitaxel association constants to commercially available HSA and AAG were ∼ 3.5 and ∼ 120 mM. Calculation using these constants and the HSA and AAG concentrations in individual patient ascites indicated that these two proteins accounted for >85% of the total protein-binding of paclitaxel in ascites. The extensive drug binding to ascites proteins, by reducing the pharmacologically active free fraction, may lead to the diminished CRS efficacy in PM patients with ascites. Clinical advances in CRS + IPC have outpaced current knowledge of pharmaceutical properties in this setting. IPC, as a locally acting therapy, is subjected to processes different from those governing systemic treatments. This study, to our knowledge, is the first to illustrate the implications of drug properties in the CRS + IPC efficacy against PM. While drugs are now an integral part of PM patient management, there is limited pharmaceutical research in this treatment setting (e.g., effects of hyperthermia or pressure on drug transport or release from delivery systems, pharmacokinetics, pharmacodynamics). Hence, CRS + IPC of PM represents an area where additional pharmaceutical research can assist further development and optimization.
Topics: Humans; Peritoneal Neoplasms; Ascites; Pharmaceutical Research; Proteomics; Tandem Mass Spectrometry; Hyperthermia, Induced; Paclitaxel; Pharmaceutical Preparations; Combined Modality Therapy; Antineoplastic Combined Chemotherapy Protocols; Colorectal Neoplasms
PubMed: 37574051
DOI: 10.1016/j.jconrel.2023.08.017 -
Cancer Science Feb 2021Peritoneal dissemination and malignant ascites in pancreatic ductal adenocarcinoma (PDAC) patients represent a major clinical issue. Lysophosphatidic acid (LPA) is a...
Peritoneal dissemination and malignant ascites in pancreatic ductal adenocarcinoma (PDAC) patients represent a major clinical issue. Lysophosphatidic acid (LPA) is a lipid mediator that modulates the progression of various cancers. Based on the increasing evidence showing that LPA is abundant in malignant ascites, we focused on autotaxin (ATX), which is a secreted enzyme that is important for the production of LPA. This study aimed to elucidate the importance of the ATX-LPA axis in malignant ascites in PDAC and to determine whether ATX works as a molecular target for treating peritoneal dissemination. In a PDAC peritoneal dissemination mouse model, the amount of ATX was significantly higher in ascites than in serum. An in vitro study using two PDAC cell lines, AsPC-1 and PANC-1, showed that ATX-LPA signaling promoted cancer cell migration via the activation of the downstream signaling, and this increased cell migration was suppressed by an ATX inhibitor, PF-8380. An in vivo study showed that PF-8380 suppressed peritoneal dissemination and decreased malignant ascites, and these results were validated by the biological analysis as well as the in vitro study. Moreover, there was a positive correlation between the amount of ATX in ascites and the degree of disseminated cancer progression. These findings demonstrated that ATX in ascites works as a promotor of peritoneal dissemination, and the targeting of ATX must represent a useful and novel therapy for peritoneal dissemination of PDAC.
Topics: Animals; Ascites; Carcinoma, Pancreatic Ductal; Female; Heterografts; Humans; Mice; Mice, Inbred BALB C; Mice, Nude; Neoplasm Invasiveness; Pancreatic Neoplasms; Peritoneal Neoplasms; Phosphoric Diester Hydrolases
PubMed: 33053268
DOI: 10.1111/cas.14689 -
The Indian Journal of Tuberculosis Oct 2022Role of Magnetic Resonance Imaging (MRI) in diagnosis of tuberculous tubo-ovarian (TO) mass.
OBJECTIVE
Role of Magnetic Resonance Imaging (MRI) in diagnosis of tuberculous tubo-ovarian (TO) mass.
METHODS
MRI was performed on 33 patients of tuberculous TO mass of female genital tuberculosis (FGTB).
RESULTS
Mean age, BMI, and parity was 27.5 ± 4.2 years, 22.7 ± 3.6 kg/m, and 0.27 ± 0.13. All patients (100%) had infertility; primary infertility (72.72%) and secondary infertility (27.23%) with mean 5.8 years. Abdominal/pelvic pain 33 (100%) cases, abdominal lump 4 (12.12%), adnexal mass 33 (100%). MRI findings showed pelvic masses 33 (100%), bilateral TO masses 11 (33.33%), cystic lesion 4 (12.12%), solid cystic lesion 3 (9.09%) with bilateral pyosalpinx 1 (3.3%), homogeneous content with ascites 1 (3.03%), rim enhancing lesion abutting pelvic wall in 1 (3.03%). Right adnexal mass 11 (33.33%), right adnexal cyst 2 (6.06%), right adnexal cystic mass in 1 (3.03%), right sided complex TO mass 1 (3.03%), right sided hydrosalpinx in 1 (3.03%) case, right sided TO mass in 4 (12.12%) cases and right sided para-ovarian cyst in 2 (6.06%). Left sided adnexal mass was seen in 11 (33.33%), cystic lesion in 1 (3.03%), ovarian cyst in 3 (9.09%) cases, left sided hydrosalpinx in 2 (6.06%), left ovarian cyst 2 (6.06%) cases, left sided ovarian cyst with encysted ascites 1 (3.03%) case and with left sided paraovarian cyst 2 (6.06%) case. Miscellaneous finding were generalised ascites (6.06%), encysted ascites (3.03%), pelvic (1; 3.03%) and mesenteric lymphadenopathy 1 (3.03%). Incidental finding were fibroid 3 (9.09%) and adenomyosis 1 (3.03%) case.
CONCLUSION
MRI appears to be useful diagnostic modality for tuberculous TO masses where differential diagnosis is malignancy but molecular diagnosis remains the gold standard.
Topics: Pregnancy; Humans; Female; Young Adult; Adult; Ascites; Tuberculosis; Magnetic Resonance Imaging; Musculoskeletal Diseases; Ovarian Cysts; Infertility; Ovarian Neoplasms
PubMed: 36460386
DOI: 10.1016/j.ijtb.2021.08.031