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Patients hospitalized with decompensated cirrhosis and a serum albumin level of less than 30 g per liter were randomly assigned to daily albumin infusions to raise the albumin level to 30 g per liter or higher or to standard care. Albumin infusions did not reduce the incidences of infection, kidney dysfunction, and death. More serious adverse events occurred in the albumin group.

Evidence is scarce on the efficacy of long-term human albumin (HA) administration in patients with decompensated cirrhosis. The human Albumin for the treatmeNt of aScites in patients With hEpatic ciRrhosis (ANSWER) study was designed to clarify this issue. We did an investigator-initiated multicentre randomised, parallel, open-label, pragmatic trial in 33 academic and non-academic Italian hospitals. We randomly assigned patients with cirrhosis and uncomplicated ascites who were treated with anti-aldosteronic drugs (≥200 mg/day) and furosemide (≥25 mg/day) to receive either standard medical treatment (SMT) or SMT plus HA (40 g twice weekly for 2 weeks, and then 40 g weekly) for up to 18 months. The primary endpoint was 18-month mortality, evaluated as difference of events and analysis of survival time in patients included in the modified intention-to-treat and per-protocol populations. This study is registered with EudraCT, number 2008–000625–19, and ClinicalTrials.gov, number NCT01288794. From April 2, 2011, to May 27, 2015, 440 patients were randomly assigned and 431 were included in the modified intention-to-treat analysis. 38 of 218 patients died in the SMT plus HA group and 46 of 213 in the SMT group. Overall 18-month survival was significantly higher in the SMT plus HA than in the SMT group (Kaplan-Meier estimates 77% vs 66%; p=0·028), resulting in a 38% reduction in the mortality hazard ratio (0·62 [95% CI 0·40–0·95]). 46 (22%) patients in the SMT group and 49 (22%) in the SMT plus HA group had grade 3–4 non-liver related adverse events. In this trial, long-term HA administration prolongs overall survival and might act as a disease modifying treatment in patients with decompensated cirrhosis. Italian Medicine Agency.

Background Malignant ascites often causes discomfort in advanced cancer patients. Paracentesis is the most common treatment modality, but it requires frequently repeated treatment. Cell-free and concentrated ascites reinfusion therapy (CART) may prolong the paracentesis interval, but controlled trials are lacking. We assessed the feasibility of a randomized controlled trial of CART vs. paracentesis alone for patients with refractory malignant ascites. Methods This study was an open-label, fast-track, randomized controlled, feasibility trial. Patients admitted to four designated cancer hospitals who received no further anticancer treatments were eligible. Patients were randomly assigned 1:1 to a CART arm or control (simple paracentesis) arm. The feasibility endpoint was the percentage of patients who completed the study intervention. Secondary endpoints included paracentesis-free survival, patient’s request on the questionnaire for paracentesis (PRO-paracentesis)-free survival (the period until the patients first reported that they would want paracentesis if indicated), and adverse events. Results We screened 953 patients for eligibility. Of 61 patients with refractory malignant ascites, 21 patients were determined as eligible. Finally, 20 patients consented and were allocated; 18 patients (90%, 95% CI: 68.3–98.8) completed the study intervention. All patients had an ECOG performance status of 3 or 4. The median drained ascites volume was 3,200 mL in the CART arm and 2,500 mL in the control arm. In the CART arm, the median reinfused albumin volume was 12.6 g. Median paracentesis-free survivals were 5 days (95% CI: 2–6) in the CART arm, and 6 days (3–9) in the control arm. Median PRO-paracentesis-free survivals were 4 days (2–5) and 5 days (1–9), respectively. A total of 73% of patients received paracentesis within 2 days from their first request for the next paracentesis. One patient in the CART arm developed Grade 1 fever. Conclusions A fast-track randomized controlled trial of CART for patients with malignant ascites is feasible. The efficacy and safety of CART should be assessed in future trials. PRO-paracentesis-free survival may be a complementary outcome measure with paracentesis-free survival in future trials. Trial registration Registered at University Hospital Medical Information Network Clinical Trial Registry as UMIN000031029 . Registered on 28/01/2018.

Background Ascites remains the most common complication of cirrhosis and a frequent reason for hospitalisation in advanced chronic liver disease (ACLD). Ascites is associated with significant symptom burden, caregiver workload and poor health-related quality of life (HRQoL). Once refractory to treatment, median survival is poor. Many with refractory ascites (RA) will neither receive a transjugular intrahepatic portosystemic shunt (TIPS) nor a liver transplant. Palliative care remains underutilised and evidence-based interventions focused on improving HRQoL are clearly needed. The standard of care for RA is repeated hospital ascites drainage with large volume paracentesis (LVP). Our earlier feasibility randomised controlled trial (RCT) (REDUCe) showed acceptability of palliative tunnelled long-term abdominal drains (LTADs), as well as preliminary evidence of safety and efficacy. The current REDUCe2 trial is a definitive national study designed to assess the impact of palliative LTADs on HRQoL in patients with RA due to ACLD. Methods/design The REDUCe2 study is a pragmatic, multicentre, open-label, mixed-methods, superiority RCT being conducted in England, Scotland and Wales. Patients with RA secondary to ACLD who are ineligible for a liver transplant or TIPS will be randomised 1:1 to receive a LTAD or continue the current standard of care (LVP). Fortnightly home research visits will be conducted for 12 weeks in both arms. The primary outcome will be liver specific HRQoL assessed at 12 weeks using the Short Form Liver Disease Quality of Life questionnaire (SFLDQoL). Secondary outcomes include assessment of symptom burden (Ascites Questionnaire), health utilities (EQ-5D-5L tool), caregiver workload (Caregiver Roles and Responsibilities Scale—CRRS questionnaire), safety (including infection, acute kidney injury and other clinical outcomes), health resource utilisation and acceptability of the intervention by patients, caregivers and healthcare professionals. We aim to recruit a total of 310 patients (155 in each arm). Discussion Effective palliative care provision remains an unmet need in ACLD. The REDUCe2 study, the largest palliative interventional trial in the UK, aims to address this inequity for this vulnerable and underserved cohort. It has the potential to generate high quality evidence to optimise and enhance palliative care in RA. Trial registration ISRCTN26993825, date registered: 15/08/2022.

We report the case of a 65‐year‐old woman with stage IVB lung adenocarcinoma who developed malignant ascites during treatment. Despite multiple ascitic fluid drainages and second‐line chemotherapy, the ascites progressively worsened. The initiation of cell‐free and concentrated ascites reinfusion therapy (CART) led to improved abdominal distention, increased blood albumin levels, and slower ascites accumulation. To our knowledge, this is the first report of CART combined with chemotherapy for the management of malignant ascites associated with lung cancer. A 65‐year‐old woman with stage IVB lung adenocarcinoma developed progressive malignant ascites despite conventional drainage and chemotherapy. Cell‐free and concentrated ascites reinfusion therapy (CART) was initiated; it relieved symptoms, increased serum albumin levels, and reduced ascites accumulation, allowing prolonged chemotherapy. This is the first reported case of CART combined with chemotherapy for malignant ascites in lung cancer.

Background Cell-free and concentrated ascites reinfusion therapy (CART) is a strategy for improving various intractable symptoms due to refractory ascites, including hypoalbuminemia. CART has recently been applied in the treatment of cancer patients. This study was performed to assess the safety of CART in a single cancer institute. Methods We retrospectively reviewed 233 CART procedures that were performed for 132 cancer patients in our institute. Results The median weight of ascites before and after concentration was 4,720 g and 490 g (median concentration rate, 10.0-fold), The median amounts of total protein and albumin were 64.0 g and 32.6 g (median recovery rates, 44.9% and 49.0%), respectively. Thirty-three adverse events (AEs) were observed in 22 (9.4%) of 233 procedures; 30 of these events occurred after reinfusion. The most common reinfusion-related AEs were fever (13 events) and chills (10 events). Univariate analyses revealed no significant relationships between the frequency of AEs and age, sex, appearance of ascites, weight of harvested and concentrated ascites, the ascites processing rate (filtration and concentration), weight of saline used for membrane cleaning, amount of calculated total protein for infusion, or prophylaxis against AEs; the reinfusion rate of ≥ 125 mL/h or ≥ 10.9 g/h of total protein affected the frequency of AEs, regardless of the prophylactic use of steroids. Conclusions The observed AEs were mainly mild reactions after reinfusion, which were related to a reinfusion rate of volume ≥ 125 mL/h, a simple indicator in practice, or total protein ≥ 10.9 g/h. Although our study was retrospective in nature and undertaken in a single institute, this information may be helpful for the management of cancer patients with refractory malignant ascites using CART.

IntroductionHuman albumin is used in the treatment of complications of cirrhosis. However, the use of long-term human albumin administration is costly and resource demanding for both patients and healthcare systems. A precision medicine approach with biomarkers to predict human albumin treatment response, so-called predictive biomarkers, could make this a viable treatment option in patients with cirrhosis and ascites.Methods and analysisALB-TRIAL is a multinational, double-blind, placebo-controlled randomised controlled trial. We aim to validate a predictive biomarker, consisting of a panel of circulating metabolites, to predict the treatment response to human albumin in patients with cirrhosis and ascites. All enrolled patients are stratified into a high-expected or low-expected effect stratum of human albumin based on the biomarker outcome. After stratification, patients in each group are randomised into either active treatment (20% human albumin) or corresponding placebo (0.9% NaCl) every 10th day for 6 months. The primary outcome is the cumulative number of liver-related events (composite of decompensation episodes, transjugular intrahepatic shunt insertion, liver transplantation and death). Key secondary outcomes include time-to-event analysis of primary outcome components, an analysis of the total healthcare burden and a health economic analysis.Ethics and disseminationThe trial obtained ethical and regulatory approval in Denmark, Germany, the Netherlands, Belgium, Hungary and Spain through the Clinical Trials Information System (CTIS) from 13 February 2023, while UK approvals from the Health Regulatory Authority, Medicines and Healthcare products Regulatory Agency and Research Ethics Committee are pending. Findings will be published in peer-reviewed journals, presented at conferences, communicated to relevant stakeholders and in the public registry of CTIS, following trial completion.Trial registration numberNCT05056220 EU CT: 2022-501006-34-01

The management of refractory ascites is critical for the treatment of patients with decompensated cirrhosis. This study aimed to evaluate the feasibility and safety of cell-free and concentrated ascites reinfusion therapy (CART) in patients with cirrhosis and refractory ascites, with a focus on changes in coagulation and fibrinolytic factors in ascitic fluid following CART. This was a retrospective cohort study including 23 patients with refractory ascites undergoing CART. Serum endotoxin activity (EA) before and after CART and the levels of coagulation and fibrinolytic factors and proinflammatory cytokines in original and processed ascitic fluid were measured. The Ascites Symptom Inventory-7 (ASI-7) scale was used for subjective symptom assessment before and after CART. Body weight and waist circumference significantly decreased after CART, whereas serum EA did not significantly change after CART. Similar to the previous reports, ascitic fluid concentrations of total protein, albumin, high-density lipoprotein cholesterol, γ-globulin, and immunoglobulin G levels were significantly increased after CART; mild elevations in body temperature and interleukin 6 and tumor necrosis factor-alpha levels in ascitic fluid were also observed. Importantly, the levels of antithrombin-III, factor VII, and X, which are useful for patients with decompensated cirrhosis, were markedly increased in the reinfused fluid during CART. Finally, the total ASI-7 score was significantly lower following CART, compared with the pre-CART score. CART is an effective and safe approach for the treatment of refractory ascites that allows the intravenous reinfusion of coagulation and fibrinolytic factors in the filtered and concentrated ascites.

Refractory or recurrent ascites is a clinical challenge frequently encountered in patients with cirrhosis. 1 – 3 The treatment options are repeated large-volume paracentesis, creation of a peritoneovenous shunt, creation of a portosystemic shunt, and liver transplantation. Elevated portal-vein pressure is a main factor in the pathogenesis of ascites. A reduction in pressure by means of the surgical creation of a portosystemic shunt 4 – 6 or transjugular intrahepatic portosystemic shunt 7 – 15 has been shown to be followed by decreased formation of ascites. With the exception of a small, randomized study 16 that found an increased rate of death among patients with ascites who were . . .

Background UK deaths due to chronic liver diseases such as cirrhosis have quadrupled over the last 40 years, making this condition now the third most common cause of premature death. Most patients with advanced cirrhosis (end-stage liver disease [ESLD]) develop ascites. This is often managed with diuretics, but if refractory, then the fluid is drained from the peritoneal cavity every 10–14 days by large volume paracentesis (LVP), a procedure requiring hospital admissions. As the life expectancy of patients with ESLD and refractory ascites (if ineligible for liver transplantation) is on average ≤ 6 months, frequent hospital visits are inappropriate from a palliative perspective. One alternative is long-term abdominal drains (LTADs), used successfully in patients whose ascites is due to malignancy. Although inserted in hospital, these drains allow ascites management outside of a hospital setting. LTADs have not been formally evaluated in patients with refractory ascites due to ESLD. Methods/design Due to uncertainty about appropriate outcome measures and whether patients with ESLD would wish or be able to participate in a study, a feasibility randomised controlled trial (RCT) was designed. Patients were consulted on trial design. We plan to recruit 48 patients with refractory ascites and randomise them (1:1) to either (1) LTAD or (2) current standard of care (LVP) for 12 weeks. Outcomes of interest include acceptability of the LTAD to patients, carers and healthcare professionals as well as recruitment and retention rates. The Integrated Palliative care Outcome Scale, the Short Form Liver Disease Quality of Life questionnaire, the EuroQol 5 dimensions instrument and carer-reported (Zarit Burden Interview) outcomes will also be assessed. Preliminary data on cost-effectiveness will be collected, and patients and healthcare professionals will be interviewed about their experience of the trial with a view to identifying barriers to recruitment. Discussion LTADs could potentially improve end-of-life care in patients with refractory ascites due to ESLD by improving symptom control, reducing hospital visits and enabling some self-management. Our trial is designed to see if such patients can be recruited, as well as to inform the design of a subsequent definitive trial. Trial registration ISRCTN, ISRCTN30697116 . Registered on 7 October 2015.