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Journal For Immunotherapy of Cancer Jun 2022Immune checkpoint inhibition (ICI) is an established therapeutic option for patients with deficient mismatch repair or high levels of microsatellite instability tumors....
Immune checkpoint inhibition (ICI) is an established therapeutic option for patients with deficient mismatch repair or high levels of microsatellite instability tumors. Yet, response to ICI among this group is varied, with nearly one-third of patients exhibiting primary resistance. Initial efforts in studying mechanisms of resistance to ICI have focused on intrinsic tumor factors. Host factors such as metastatic niches have unique biological properties that may mediate resistance to ICI but have been less studied date. Patients with metastatic d-MMR/MSI-H gastrointestinal cancers and peritoneal metastases (PM) who had concurrent ascites have been recently shown to have worse outcomes with ICI therapy compared with patients with PM without ascites and patients with non-PM metastases. The juxtaposition of tumors with an intrinsic sensitivity to ICI failing to respond by virtue of the presence of ascites within the peritoneum, brings to the forefront the critical role of the metastatic niche. In this commentary, we discuss mechanisms for ICI resistance that may arise from the immunoprivileged state of the peritoneal cavity, paracrine factors within malignant ascites or tumor-peritoneum interactions. An improved understanding of the peritoneal microenvironment and the use of peritoneal-directed therapies may ameliorate the modest benefit of ICIs in this unique clinical entity.
Topics: Ascites; Humans; Immune Checkpoint Inhibitors; Immunotherapy; Neoplasms; Peritoneum; Tumor Microenvironment
PubMed: 35728873
DOI: 10.1136/jitc-2022-004749 -
World Journal of Surgical Oncology Dec 2020To fully assess the quality of the guidelines for the management of malignant pleural effusions (MPE) and ascites and reveal the heterogeneity of recommendations and... (Review)
Review
OBJECTIVES
To fully assess the quality of the guidelines for the management of malignant pleural effusions (MPE) and ascites and reveal the heterogeneity of recommendations and possible reasons among guidelines.
METHODS
A systematic search was performed in the database to obtain guidelines for the management of MPE and ascites. The AGREE IIGtool was used to assess the quality of these guidelines. The Measurement Scale of Rate of Agreement (MSRA) was introduced to assess the scientific agreement of formulated recommendations for the management of MPE and ascites among guidelines, and evidence supporting these recommendations was extracted and analyzed.
RESULTS
Nine guidelines were identified. Only 4 guidelines scored more than 60% and are worth recommending. Recommendations were also heterogeneous among guidelines for the management of MPE, and the main reasons were the different emphases of the recommendations for the treatment of MPE, the contradictions in recommendations, and the unreasonably cited evidence for MPE.
CONCLUSIONS
The quality of the management guidelines for patients with MPE and malignant ascites was highly variable. Specific improvement of the factors leading to the heterogeneity of recommendations will be a reasonable and effective way for developers to upgrade the recommendations in the guidelines for MPE.
Topics: Ascites; Humans; Pleural Effusion, Malignant; Prognosis
PubMed: 33308239
DOI: 10.1186/s12957-020-02097-y -
International Journal of Molecular... Apr 2021Although malignant ascites (MAs) are known to contribute to various aspects of ovarian cancer progression, knowledge regarding their role in the adhesion of cancer cells...
Although malignant ascites (MAs) are known to contribute to various aspects of ovarian cancer progression, knowledge regarding their role in the adhesion of cancer cells to normal peritoneal cells is incomplete. Here, we compared the effect of MAs and benign ascites (BAs) on the adhesion of A2780 and OVCAR-3 cancer cells to omentum-derived peritoneal mesothelial cells (PMCs) and peritoneal fibroblasts (PFBs). The results showed that MAs stimulated the adhesion of A2780 and OVCAR-3 cells to PMCs and PFBs more efficiently than did BAs, and the strongest binding occurred when both cancer and normal cells were exposed to the fluid. Intervention studies showed that MAs-driven adhesion of A2780 cells to PMCs/PFBs depends on the presence of TGF-β1 and HGF, whereas binding of OVCAR-3 cells was mediated by TGF-β1, GRO-1, and IGF-1. Moreover, MAs upregulated α5β1 integrin expression on PFBs but not on PMCs or cancer cells, vimentin expression in all cells tested, and ICAM-1 only in cancer cells. When integrin-linked kinase was neutralized in PMCs or PFBs, cancer cell adhesion to PMCs and PFBs decreased. Collectively, our report shows that MAs may contribute to the early stages of ovarian cancer metastasis by modulating the proadhesive interplay between normal and cancer cells.
Topics: Apoptosis; Ascites; Carcinoma, Ovarian Epithelial; Cell Adhesion; Cell Line, Tumor; Cells, Cultured; Female; Fibroblasts; Flow Cytometry; Fluorescent Antibody Technique; Humans; Ovarian Neoplasms; Peritoneal Neoplasms; Peritoneum
PubMed: 33921783
DOI: 10.3390/ijms22084222 -
BMC Gastroenterology Nov 2023Transjugular intrahepatic portosystemic shunt (TIPS) is a well-validated treatment option for clinically significant portal hypertension (CSPH) in the context of liver... (Review)
Review
BACKGROUND
Transjugular intrahepatic portosystemic shunt (TIPS) is a well-validated treatment option for clinically significant portal hypertension (CSPH) in the context of liver cirrhosis. Its high efficacy and safety in the management of treatment-refractory ascites and variceal bleeding have been extensively proven. Contraindications for TIPS include severe right heart failure, hepatic encephalopathy, and sepsis. However, the role of liver malignancy in TIPS is debatable. Mostly, primary liver malignancies such as hepatocellular carcinoma (HCC) emerge from advanced liver diseases. Coexisting portal hypertension in HCC often results in limited treatment options and a poor prognosis. Previous studies have shown that TIPS implantation in patients with HCC is technically feasible and is usually not associated with major adverse events. Furthermore, TIPS may help in bridging the time to liver transplantation in early HCC and allow for locoregional treatment in advanced HCC. However, several studies suggest that seeding tumour cells to the lungs by TIPS placement might worsen the prognosis.
CONCLUSIONS
TIPS placement in patients with coexisting liver malignancy remains a case-by-case decision, and there is no profound evidence allowing general recommendations. This review aims to provide a state-of-the-art overview of the potential risks and benefits of TIPS placement in patients with liver malignancies.
Topics: Humans; Carcinoma, Hepatocellular; Liver Neoplasms; Esophageal and Gastric Varices; Portasystemic Shunt, Transjugular Intrahepatic; Treatment Outcome; Gastrointestinal Hemorrhage; Hypertension, Portal; Liver Cirrhosis; Risk Assessment; Ascites
PubMed: 37986043
DOI: 10.1186/s12876-023-03047-0 -
BMC Gastroenterology Sep 2022Malignancy-related ascites accounts for approximately 10% of causes of ascites. Our AIM was to characterize the ascites fluid and correlate clinical outcomes in those...
BACKGROUND
Malignancy-related ascites accounts for approximately 10% of causes of ascites. Our AIM was to characterize the ascites fluid and correlate clinical outcomes in those with extrahepatic malignancy and ascites.
METHODS
241 subjects with extrahepatic solid tumors and ascites were reviewed from 1/1/2000 to 12/31/2019, 119 without liver metastasis and 122 with liver metastasis.
RESULTS
Ascites fluid consistent with peritoneal carcinomatosis (PC) was most common, 150/241 (62%), followed by fluid reflecting the presence of portal hypertension (PH), 69/241 (29%). 22/241 (9%) had low SAAG and low ascites fluid total protein, with evidence of PC on cytology and or imaging in 20/22. Lung cancer was the most common malignancy in subjects with ascites due to PC at 36/150 (24%), pancreatic cancer was the most common in subjects with ascites with features of PH at 16/69 (23%). Chemotherapy or immunotherapy alone was the most common management approach. Significantly higher 5-year, 3-year and 1-year mortality rate were noted in subjects with evidence of PC on cytology/imaging versus subjects with no evidence of PC, and in subjects with liver metastasis compared to subjects without liver metastasis. Subjects with pancreatic cancer and evidence of PC on cytology/imaging had higher 1 and 5-year mortality rates compared to subjects without PC.
CONCLUSIONS
Ascites in solid tumor malignancy is most commonly due to PC. We also observed ascites fluid with characteristics of PH in 29% of subjects. Higher mortality rates in subjects with peritoneal carcinomatosis and liver metastasis were noted. These findings may help inform prognosis and treatment strategies.
Topics: Ascites; Ascitic Fluid; Humans; Hypertension, Portal; Liver Neoplasms; Pancreatic Neoplasms; Peritoneal Neoplasms
PubMed: 36064324
DOI: 10.1186/s12876-022-02487-4 -
Methods in Molecular Biology (Clifton,... 2023The 3D-autologous culture method (3D-ACM) for patient-derived cancer samples utilizes a patient's own body fluid or serum to prepare a 3D scaffold and for the culture...
The 3D-autologous culture method (3D-ACM) for patient-derived cancer samples utilizes a patient's own body fluid or serum to prepare a 3D scaffold and for the culture medium. 3D-ACM enables tumor cells and/or tissues from an individual patient to proliferate in vitro, in a microenvironment that is very similar to their original, in vivo surroundings. The purpose is to maximally preserve in culture the native biological properties of a tumor. This technique has been employed for two models: (1) cells isolated from malignant ascites or pleural effusions (body fluids) and (2) solid tissues from biopsies or surgically removed cancers. Here we describe the detailed procedures for these 3D-ACM models.
Topics: Humans; Neoplasms; Precision Medicine; Pleural Effusion; Ascites; Tumor Microenvironment
PubMed: 37191790
DOI: 10.1007/978-1-0716-3163-8_5 -
Advanced Science (Weinheim,... Jul 2023Malignant ascites in advanced hepatocellular carcinoma (HCC) is a complex clinical problem that lacks effective treatments. Due to the insensitivity of advanced HCC...
Malignant ascites in advanced hepatocellular carcinoma (HCC) is a complex clinical problem that lacks effective treatments. Due to the insensitivity of advanced HCC cells to traditional chemotherapies, low drug accumulation, and limited drug residence time in the peritoneal cavity, the therapeutic effects of malignant ascites in HCC are not satisfactory. In this study, an injectable hydrogel drug delivery system based on chitosan hydrochloride and oxidized dextran (CH-OD) is designed to load sulfasalazine (SSZ), an FDA-approved drug with ferroptosis-inducing ability, for effective tumor-killing and activation of anti-tumor immunity. Compared to free SSZ, SSZ-loaded CH-OD (CH-OD-SSZ) hydrogel exhibits greater cytotoxicity and induces higher levels of immunogenic ferroptosis. In the preclinical model of hepatoma ascites, intraperitoneal administration of CH-OD-SSZ hydrogel can significantly suppress tumor progression and improve the immune landscape. Both in vitro and in vivo, CH-OD-SSZ hydrogel induces the repolarization of macrophages to an M1-like phenotype and promotes the maturation and activation of dendritic cells. Combination treatment with CH-OD-SSZ hydrogel and anti-programmed cell death protein 1 (PD-1) immunotherapy achieves more than 50% ascites regression and generates long-term immune memory. Collectively, CH-OD-SSZ hydrogel exhibits promising therapeutic potential in the treatment of peritoneal dissemination and malignant ascites in advanced HCC, especially when combined with anti-PD-1 immunotherapy.
Topics: Humans; Carcinoma, Hepatocellular; Hydrogels; Chitosan; Dextrans; Ascites; Ferroptosis; Liver Neoplasms; Sulfasalazine; Immunotherapy
PubMed: 37132587
DOI: 10.1002/advs.202300517 -
Expert Review of Anticancer Therapy Jul 2020Proactive palliative care can effectively relieve symptoms early and effectively as well as improve the quality of life of patients with gastric adenocarcinoma (GAC). (Review)
Review
INTRODUCTION
Proactive palliative care can effectively relieve symptoms early and effectively as well as improve the quality of life of patients with gastric adenocarcinoma (GAC).
AREAS COVERED
The review summarizes palliative care for GAC. GAC caused specific symptoms, such as malignant gastric outlet obstruction (GOO), bleeding, weight loss, and/or ascites, therefore, these symptoms must be addressed specifically.
EXPERT OPINION
Palliative care should start early to control general symptoms, thus may improve the patient's condition to make the patient eligible for anti-cancer treatment. As some stage IV GAC patients can now live longer, palliative interventions become more important. A multimodality interdisciplinary approach is strongly encouraged.
Topics: Adenocarcinoma; Ascites; Gastric Outlet Obstruction; Gastrointestinal Hemorrhage; Humans; Neoplasm Staging; Palliative Care; Quality of Life; Stomach Neoplasms; Weight Loss
PubMed: 32543938
DOI: 10.1080/14737140.2020.1781620 -
Journal For Immunotherapy of Cancer Apr 2023High-grade serous ovarian carcinoma (HGSC) is the most lethal gynecologic malignancy characterized by resistance to chemotherapy and high rates of recurrence. HGSC...
BACKGROUND
High-grade serous ovarian carcinoma (HGSC) is the most lethal gynecologic malignancy characterized by resistance to chemotherapy and high rates of recurrence. HGSC tumors display a high prevalence of tumor suppressor gene loss. Given the type 1 interferon regulatory function of and genes and their associated contrasting T-cell infiltrated and non-infiltrated tumor immune microenvironment (TIME) states, respectively, in this study we investigated the potential of stimulator of interferon genes (STING) pathway activation in improving overall survival via enhancing chemotherapy response, specifically in tumors with PTEN deficiency.
METHODS
Expression of PTEN protein was evaluated in tissue microarrays generated using pretreatment tumors collected from a cohort of 110 patients with HGSC. Multiplex immunofluorescence staining was performed to determine spatial profiles and density of selected lymphoid and myeloid cells. In vivo studies using the syngeneic murine HGSC cell lines, ID8- ; and ID8- ; , were conducted to characterize the TIME and response to carboplatin chemotherapy in combination with exogenous STING activation therapy.
RESULTS
Patient tumors with absence of PTEN protein exhibited a significantly decreased disease specific survival and intraepithelial CD68+ macrophage infiltration as compared with intact PTEN expression. In vivo studies demonstrated that -deficient ovarian cancer cells establish an immunosuppressed TIME characterized by increased proportions of M2-like macrophages, GR1+MDSCs in the ascites, and reduced effector CD8+ cytotoxic T-cell function compared with -deficient cells; further, tumors from mice injected with -deficient ID8 cells exhibited an aggressive behavior due to suppressive macrophage dominance in the malignant ascites. In combination with chemotherapy, exogenous STING activation resulted in longer overall survival in mice injected with -deficient ID8 cells, reprogrammed intraperitoneal M2-like macrophages derived from -deficient ascites to M1-like phenotype and rescued CD8+ cytotoxic T-cell activation.
CONCLUSIONS
This study reveals the importance of considering the influence of cancer cell intrinsic genetic alterations on the TIME for therapeutic selection. We establish the rationale for the optimal incorporation of interferon activating therapies as a novel combination strategy in PTEN-deficient HGSC.
Topics: Humans; Mice; Female; Animals; PTEN Phosphohydrolase; Ascites; Ovarian Neoplasms; Antineoplastic Agents; Genotype; Interferons; Tumor Microenvironment
PubMed: 37015760
DOI: 10.1136/jitc-2022-006170 -
Annals of Surgery Nov 2023To compare minimally invasive (MILR) and open liver resections (OLRs) for hepatocellular carcinoma (HCC) in patients with metabolic syndrome (MS).
OBJECTIVE
To compare minimally invasive (MILR) and open liver resections (OLRs) for hepatocellular carcinoma (HCC) in patients with metabolic syndrome (MS).
BACKGROUND
Liver resections for HCC on MS are associated with high perioperative morbidity and mortality. No data on the minimally invasive approach in this setting exist.
MATERIAL AND METHODS
A multicenter study involving 24 institutions was conducted. Propensity scores were calculated, and inverse probability weighting was used to weight comparisons. Short-term and long-term outcomes were investigated.
RESULTS
A total of 996 patients were included: 580 in OLR and 416 in MILR. After weighing, groups were well matched. Blood loss was similar between groups (OLR 275.9±3.1 vs MILR 226±4.0, P =0.146). There were no significant differences in 90-day morbidity (38.9% vs 31.9% OLRs and MILRs, P =0.08) and mortality (2.4% vs 2.2% OLRs and MILRs, P =0.84). MILRs were associated with lower rates of major complications (9.3% vs 15.3%, P =0.015), posthepatectomy liver failure (0.6% vs 4.3%, P =0.008), and bile leaks (2.2% vs 6.4%, P =0.003); ascites was significantly lower at postoperative day 1 (2.7% vs 8.1%, P =0.002) and day 3 (3.1% vs 11.4%, P <0.001); hospital stay was significantly shorter (5.8±1.9 vs 7.5±1.7, P <0.001). There was no significant difference in overall survival and disease-free survival.
CONCLUSIONS
MILR for HCC on MS is associated with equivalent perioperative and oncological outcomes to OLRs. Fewer major complications, posthepatectomy liver failures, ascites, and bile leaks can be obtained, with a shorter hospital stay. The combination of lower short-term severe morbidity and equivalent oncologic outcomes favor MILR for MS when feasible.
Topics: Humans; Carcinoma, Hepatocellular; Liver Neoplasms; Ascites; Metabolic Syndrome; Hepatectomy; Propensity Score; Liver Failure; Length of Stay; Laparoscopy; Retrospective Studies; Postoperative Complications
PubMed: 36994755
DOI: 10.1097/SLA.0000000000005861