Ascites Reinfusion Research Articles

Cell-Free and Concentrated Ascites Reinfusion Therapy Is More Effective for Refractory Ascites in Patients with Autosomal Dominant Polycystic Kidney Disease

Cell-Free and Concentrated Ascites Reinfusion Therapy Is More Effective for Refractory Ascites in Patients with Autosomal Dominant Polycystic Kidney Disease

Drainage of ascites in cirrhosis.

For cirrhotic refractory ascites, diuretics combined with albumin and vasoactive drugs are the first-line choice for ascites management. However, their therapeutic effects are limited, and most refractory ascites do not respond to medication treatment, necessitating consideration of drainage or surgical interventions. Consequently, numerous drainage methods for cirrhotic ascites have emerged, including large-volume paracentesis, transjugular intrahepatic portosystemic shunt, peritoneovenous shunt, automated low-flow ascites pump, cell-free and concentrated ascites reinfusion therapy, and peritoneal catheter drainage. This review introduces the advantages and disadvantages of these methods in different aspects, as well as indications and contraindications for this disease.

Effectiveness and Safety of Cell-Free and Concentrated Ascites Reinfusion Therapy in the Treatment of Gynecological Malignancy-Related Ascites: A Systematic Review and Meta-Analysis

Introduction: Gynecological malignancy-related ascites (GMRA) cause discomfort symptoms in advanced gynecological cancer patients, especially in ovarian cancer. Cell-free and concentrated ascites reinfusion therapy (CART) is a palliative treatment for GMRA. Methods: Literature was searched from PubMed, CENTRAL, and Web of Science for relevant studies in all languages through May 31, 2024. The effectiveness of CART for GMRA was identified from data provided by full articles, brief reports, and conference abstracts. Results: Seven studies, comprising 166 patients with GMRA and 387 CART procedures, were examined in this study. The mean volume of GMRA obtained and reinfused after concentrating was 3.95 L (95% confidence interval [CI] 3.25–4.26 L) and 0.51 L (95% CI 0.38–0.65), respectively. Total protein and albumin reinfused were 98.6 g (95% CI 75.4–121.8 g) and 44.8 g (95% CI 37.2–52.5 g) on average, respectively. The mean CART-CART interval was 26.9 days (95% CI 24.2–29.7). No severe adverse events were observed during the CART procedures. Conclusions: CART is considered one of the palliative therapies for GMRA with proven safety and effectiveness.

Feasibility and efficacy of cell-free and concentrate ascites reinfusion therapy (CART) for advanced pancreatic cancer patients with massive malignant ascites

BackgroundThe management of malignant ascites is critical for treating patients with advanced pancreatic cancer. The purpose of this study was to assess the safety of cell-free and concentrated ascites reinfusion therapy (CART) and its impact on the prognosis of patients with advanced pancreatic cancer who have massive malignant ascites. MethodsThis study analyzed 47 procedures in 29 patients who underwent CART for ascites caused by pancreatic cancer between 2015 and 2022. Among them, 7 patients who received chemotherapy following CART were classified as the chemotherapy group, while 22 patients without chemotherapy after CART were classified as the palliative care group. ResultsAmong the 47 procedures, adverse events (AEs) were observed in 9 procedures (19 %). Grade 2 adverse events were observed only in one procedure, manifested as fever. There were no grade 3 or 4 AEs, nor were there any treatment-related deaths. The median survival time was 4.0 months in the chemotherapy group and 0.7 months in the palliative care group (p = 0.004). The albumin level in the chemotherapy group was significantly higher than that in the palliative care group. ConclusionCART is feasible and might be the optimal option to enable prolonged use of chemotherapy to improve the prognosis for late-stage pancreatic cancer patients.

Narrative review of malignant ascites: epidemiology, pathophysiology, assessment, and treatment.

Malignant ascites (MA) is common in patients with advanced cancer, and about 60% of patients with MA experience distressing symptoms. In addition, MA has been identified as a poor prognostic factor, therefore, making the management of MA an important issue. We aimed to review literature describing MA provide a narrative synthesis of relevant studies. A literature search of articles published between 1971 and May 2023 was performed in PubMed, and Cochrane library using the words "ascites/malignant ascites" and the theme of each section. Authors independently selected the articles used and summarized. Finally, this manuscript was obtained consensus through discussed among all authors. The pathophysiological mechanism of ascites formation involves increased vascular permeability and impaired fluid drainage through the lymphatic system, which explain the occurrence of peritoneal carcinomatosis, portal hypertension due to liver tumors, liver cirrhosis in the background of hepatocellular carcinoma, and Budd-Chiari syndrome caused by tumor occlusion of the hepatic vein. The efficacy and safety of various treatments and procedures have been investigated previously; however, no treatment guidelines have been established yet. Diuretics and paracentesis are often selected as the first lines of treatment. Intraperitoneal drug administration (catumaxomab, bevacizumab, aflibercept, hyperthermic intraperitoneal chemotherapy, triamcinolone), indwelling peritoneal catheters, peritoneovenous shunting, and cell-free and concentrated ascites reinfusion therapy are commonly used to manage refractory ascites. A new device for this purpose is alfapump, which transfers ascites fluid from the peritoneum into the urinary bladder. In addition, thoracic epidural analgesia may be effective for managing ascites-related symptoms. Despite these options, no standard treatment for MA has been established yet because few trials have been conducted in this area. There are many issues to be investigated, and future research and treatment development are expected.

Assessing protein and albumin recovery rates in different ascites filtration membrane washing methods for cell-free and concentrated ascites reinfusion therapy.

In cell-free and concentrated ascites reinfusion therapy (CART), the protein recovery rate decreases when the filtration membrane gets clogged. Employing a device with a filtration membrane washing feature prevents clogging, but it leads to the loss of ascites within the filter, resulting in reduced protein recovery. This study employed a device with a membrane washing function to investigate the relationship between protein recovery rate and the quantity of washing solution used, depending on the selected washing method. We analyzed cases of CART conducted at Fujita Health University Hospital between May 2021 and November 2022. The cases were divided and compared between two groups: one using flush and rinse as the washing method (flush+rinse group) and another using only flushing (flush group). We identified nine cases and 16 sessions. In the flush+rinse group, the median amount of washing solution used per membrane washing was 259mL per cycle, whereas it was 54mL per cycle in the flush group. This difference was statistically significant (p<0.0001). The median total protein recovery rate was 53.8% for the flush+rinse group and 78.8% for the flush group, with the latter showing a significantly higher value (p=0.0199). In CART using a membrane washing function, adopting a washing method that reduces the amount of washing solution leads to an increase in the total protein recovery rate.

Reappraisal of a Renovated Cell-free and Concentrated Ascites Reinfusion Therapy for Malignant Ascites.

Cell-free and concentrated ascites reinfusion therapy (CART) was established for refractory ascites and renovated CART (Keisuke Matsusaki (KM) -CART) has been recently developed especially for malignant ascites; however, the actual clinical efficacy of KM-CART has been rarely reported. We performed 226 KM-CART procedures in 104 patients with malignant ascites in three hospitals from August 2013 to September 2018. Medical records were retrospectively reviewed for ascites data, related complications, symptoms before and after each CART and prognosis after the first CART. The modified Glasgow Prognostic Score (mGPS) was reviewed before every procedure, as an indicator of nutritional status. Pancreatic cancer was the most common indication for the KM-CART procedure, followed by gastric cancer, hepatocellular carcinoma, ovarian cancer, and cholangiocarcinoma (five major diseases). The 50% survival times of these five major diseases after the first procedure were 25, 39, 31, 49, and 33 days, respectively. The mean survival time for all patients was 73.5 days, and 75.6 days for those with the five major diseases. All patients experienced symptomatic relief, and complications were rare. Repeated KM-CART was performed in 47.1% of the patients, most often in those with ovarian cancer (66.7%). Regarding the mGPS at the first CART procedure, 89% of patients were in the group with the poorest nutritional status. Patients who underwent KM-CART three or more times had longer survival than those who were treated once or twice. Repeated KM-CART provides a survival benefit for patients with malignant ascites, even in cases of poor nutritional status.

Combined Intraperitoneal Paclitaxel and Systemic Chemotherapy for Patients with Massive Malignant Ascites Secondary to Pancreatic Cancer: A Report of Two Patients.

The prognosis of patients with peritoneal metastases from pancreatic cancer is poor, largely due to massive ascites, which precludes systemic treatment. Two patients with a poor performance status and malignant ascites were treated with cell-free and concentrated ascites reinfusion therapy followed by combined chemotherapy with intraperitoneal paclitaxel, intravenous gemcitabine, and nab-paclitaxel. These patients achieved a survival of 19 and 36 weeks with a relatively good quality of life. Combined intraperitoneal paclitaxel and systemic chemotherapy may provide effective palliative management for some patients with peritoneal metastases from pancreatic cancer.

Reinfusion of peritoneal fluid elevates the level of plasma D-dimer in patients with early-onset ovarian hyperstimulation syndrome.

This study aimed to elucidate the factors that affect the dynamics of blood D-dimer in ovarian hyperstimulation syndrome (OHSS). We retrospectively reviewed medical records from two hospitals and extracted data obtained during assisted reproductive technology and OHSS treatment. Blood D-dimer levels during hospitalization were plotted against body weight. Other factors possibly related to blood D-dimer levels were also analyzed. The analysis included 10 patients with OHSS admitted between January 2013 and June 2023. In all patients, blood D-dimer levels increased significantly when they convalesced from OHSS and lost weight. None of the patients showed clinical signs of thrombosis, which was confirmed using imaging tests in 8 of 10 patients. Two patients underwent cell-free and concentrated ascites reinfusion therapy (CART), and their blood D-dimer levels increased dramatically after the procedure. Weight change and CART are associated with blood D-dimer dynamics in OHSS. Our results show that elevated blood D-dimer levels in patients with OHSS do not always represent the presence of thrombosis. Reinfusion of pooled D-dimer in ascites may explain the D-dimer surge during the recovery phase or after CART in these patients. Our study provides new perspectives on the clinical implications of D-dimer during OHSS.

Massive neoplastic ascites

Peritoneal metastases frequently occur in primary or recurrent abdominal malignancy and are often associated with massive ascites, which determines severe abdominal bloating, respiratory distress, and poor quality of life in patients with few months of life. After the failure of traditional medical therapies, simple drainage is effective in providing temporary symptom relief but does not provide a durable solution. Several treatment options are available, but no standard treatment strategy has been established, and none of the treatments consistently showed the ability to extend life expectancy. This review focuses on outcomes and adverse events of simple drainage, catheter placement, intraperitoneal therapy, peritoneovenous shunting, hyperthermic intraperitoneal chemotherapy, early postoperative intraperitoneal chemotherapy, pressurized intraperitoneal aerosol chemotherapy, and cell-free and concentrated ascites reinfusion therapy. The choice between the available options for durable symptom management requires both care and caution in weighing risks and benefits according to the patient’s life expectancy.

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.

Novel and highly reliable leak check tests for drop- and external pressure-type cell-free and concentrated ascites reinfusion therapy.

For safe management of cell-free and concentrated ascites reinfusion therapy (CART), a highly reliable leak test for detecting ascites filter damage is essential. However, such a test has not been established for drop-type CART. We devised two novel leak tests for drop- and external pressure-type CART, manual or pump pressurization methods, using high-pressure loading and pressure monitoring, and investigated their reliability. Both methods could easily load and maintain sufficiently high pressure (>400 Torr) on the hollow fibers for 2 min. No result deviation was noted between different operators. The pressure drops in both methods were identical and significantly lower than those in the leak test using a special CART machine, the e-CART. The reliability of our revised leak test is equivalent to that of the automatic leak test of e-CART. These highly reliable leak tests may contribute to safety in patients undergoing drop- and external pressure-type CART.

Management of cirrhotic ascites: Seven-step treatment protocol based on the Japanese evidence-based clinical practice guidelines for liver cirrhosis 2020.

Liver cirrhosis is a severe illness, associated with multiple complications, which can lead to liver failure. One of the major complications of cirrhosis is ascites. This review describes a stepped treatment approach for the management of ascites in Japanese patients with cirrhosis. It is broadly based on the 2020 update of the Japanese clinical practice guidelines for liver cirrhosis, which is briefly compared with guidelines from Europe and the United States. Step 1 is sodium restriction at a level suitable for Japanese individuals (5-7 g/day), Step 2 is albumin treatment to counteract underlying hypoalbuminemia, Step 3 is initiation of diuretic treatment with spironolactone, followed by add-on loop diuretic treatment at Step 4. Patients refractory to sodium restriction and sodium diuretics can be treated with tolvaptan (Step 5) - a vasopressin V2 receptor antagonit that is available in Japan. Patients at Steps 6 and 7 have refractory ascites and are treated with large volume paracentesis (LVP) in combination with an albumin infusion. High-dose albumin infusion (6-8 g/L) at the time of LVP has recently become possible in Japan. Cell-free and concentrated ascites reinfusion therapy (CART) is also an option at Step 6. Two of the treatment options at Step 7 are limited in Japan (transjugular intrahepatic portosystemic shunts are not approved, and access to liver donors is very limited), but patients can undergo a peritoneovenous shunt if no other options are available. While challenges remain in the treatment of ascites, adopting this stepwise treatment approach may improve patient outcomes. This article is protected by copyright. All rights reserved.

RENAL3: Hybrid Concentration Method of Ascites Filtration and Concentration Equipment for Cell-free and Concentrated Ascites Reinfusion Therapy

Study: As a safe and effective treatment for refractory ascites, more than 30,000 cases of Cell-free and concentrated ascites reinfusion therapy (CART) are performed annually in Japan. In ascites processing, concentration has been performed at a fixed concentration ratio (constant ratio concentration) with a standard value of 10-fold concentration. However, as the main target disease for CART has shifted from cirrhosis to cancerous peritonitis, it has become necessary to deal with the clogging of the concentration filter when processing large amounts of cancerous ascites with high protein concentrations. Our technology for self-regulation function of the concentration ratio has been introduced into M-CART and other CART specialized equipment, enabling safe automatic concentration within set pressure range (constant pressure concentration). However, when treating ascites with low protein concentration, constant pressure concentration at a high concentration ratio may enhance protein leakage into the waste fluid and reduce protein recovery rate. Therefore, we devised a hybrid concentration method that combines constant pressure and constant ratio concentration, and investigated its usefulness in improving protein recovery by using simulated ascites and analyzing multicenter clinical evaluations. Methods: In the experiment, simulated ascites using substitute plasma agent (hydroxyethylated starch, HSE) was used to simulate cancerous ascites. In the clinical evaluation, 129 sessions of CART performed using M-CART were examined. Results: In the experiment, as the control pressure was increased, the waste fluid volume and HSE concentration in the waste fluid increased and the recovery rate decreased. In the analysis of clinical cases, protein recovery rate was lower in cases where constant pressure concentration was performed. These results indicate that constant-pressure concentration at a high concentration ratio in ascites with a low protein concentration risks decreasing the protein recovery rate, and that the hybrid concentration method enables concentration with a high recovery rate according to the condition of the ascites fluid.

Occurrence of fever in cell-free and concentrated ascites reinfusion therapy is not related to the primary disease or nature of ascites.

Cell-free and concentrated ascites reinfusion therapy (CART) is a treatment for refractory ascites wherein filtered and concentrated ascitic fluid is reinfused. Although fever is one of the side effects of CART, its cause is not clear. Patients who underwent at least one CART session between June 2011 and May 2021 at our medical center were retrospectively enrolled in the study. They were classified according to the primary disease and nature of ascites. Ninety patients were included in this study. Increase in body temperature (BT) after CART was observed, regardless of the primary disease and nature of ascites. The difference in temperature before and after CART did not differ based on the primary disease [cancerous (including hepatocellular carcinoma, ovarian cancer) and non-cancerous] and nature of ascites. Elevated BT and fever after CART are not related to the primary disease and nature of the ascites.

Hemodynamic Variability During Drainage of Large Volumes of Malignant Ascites in Patients With Cancer.

This study compared the variability in mean arterial pressure (MAP) during drainage of ascites in patients with cancer who underwent drainage of a large (5-10 L) or small (<5 L) volume of ascites. We prospectively enrolled 50 patients scheduled for cell-free and concentrated ascites reinfusion therapy. Equivalence was considered to be established if the 95% confidence interval (95% CI) for the highest variability rate of MAP was within ±20%. The median volume of ascites removed was 3.30 L (95% CI [2.84, 4.40]) in the small-drainage-volume group (n = 15) and 6.75 L (95% CI [6.40, 7.30]) in the large-drainage-volume group (n = 34). The 95% CIs for the highest variability rates in MAP ranged from -19.60 to -6.23 and from -19.16 to -12.95 (p = .594), respectively, indicating equivalence. These findings indicate that variability in MAP during drainage of ascites is not dependent on drainage volume.

Cell-free and concentrated ascites reinfusion therapy versus large-volume paracentesis for the treatment of cirrhotic patients with refractory ascites: A multicenter prospective observational study.

Cell-free and concentrated ascites reinfusion therapy (CART) and large-volume paracentesis (LVP) with albumin infusion are useful for managing refractory ascites (RA). However, it remains unclear which therapy is more effective in patients with cirrhosis with RA. From June 2018 to March 2022, 25 patients with RA treated with CART or LVP with albumin infusion were enrolled in this multicenter prospective observational study to investigate the number of abdominal paracenteses, albumin preparations used, and drainage volume during an 8-week observation period. Among all patients at entry (median age, 63years; 52% men; 60% Child-Pugh B and 40% Child-Pugh C), 92% were treated with furosemide (median, 20mg/day), 92% with spironolactone (25mg/day), and all with tolvaptan (7.5mg/day). Patients with RA had a poor health-related quality of life (HRQOL) and prominent ascites-related symptoms. Four of the 20 eligible patients were treated with CART, 11 with LVP with albumin infusion, and five with their combination. The median number of paracenteses, total drainage volume, and albumin infusions were 1.5, 7.4L, and 0, respectively, in the CART group; 5.0, 22.0L, and 5.0, respectively, in the LVP group; and 5.0, 30.0L, and 5.0, respectively in their combination group. The treatment effects did not differ significantly among the three groups regarding weight loss, liver function, renal function, electrolytes, and HRQOL. However, patients treated with CART had fewer paracenteses and albumin infusions than those treated with LVP. CART and LVP have comparable therapeutic efficacy for RA in patients with cirrhosis.

IFN-γ and IL-12 from Concentrated Ascites in Patients with Pancreatic Cancer Exerts Growth Inhibitory Effects against Pancreatic Cancer Cells

Patients with pancreatic cancer (PC) often suffer from refractory ascites associated with peritoneal metastasis. This severely impairs activities of daily living and leads to an unfavorable prognosis. Cell-free and concentrated ascites reinfusion therapy (CART) has attracted attention as a promising therapy for relieving the symptoms of malignant ascites. Accumulating evidence suggests that malignant ascites contains a variety of soluble factors, such as cytokines, that can be beneficial or detrimental in the prognosis of patients with refractory ascites. However, the expression profiles of these cytokines in the ascites before and after CART remain unknown. In this study, we used a comprehensive cytokine array to measure the expression levels of 102 cytokines in ascites derived from patients with PC before and after CART. The assay results revealed that the concentrations of several cytokines exacerbating tumor angiogenesis and tumor-suppressive interferon-gamma (IFN-γ) and interleukin-12 (IL-12) were higher in ascites after CART than before CART. Interestingly, growth of KP-2 human PC cells following exposure to ascites after CART decreased considerably compared to that before CART. Concomitant treatment of neutralizing antibodies against IFN-γ or IL-12 with ascites after CART restored the growth of KP-2 cells to the control level. These findings indicate that IFN-γ and IL-12 in ascites after CART may contribute to the inhibited growth of PC cells, highlighting their potential as biomarkers for assessing the clinical efficacy of CART procedures in patients with PC.

REN4: Concentration Ratio Self-regulation Function of Ascites Filtration and Concentration Equipment for Cell-free and Concentrated Ascites Reinfusion Therapy

REN4: Concentration Ratio Self-regulation Function of Ascites Filtration and Concentration Equipment for Cell-free and Concentrated Ascites Reinfusion Therapy

Adverse effects of cell-free and concentrated ascites reinfusion therapy for malignant ascites: a single-institute experience

BackgroundCell-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.MethodsWe retrospectively reviewed 233 CART procedures that were performed for 132 cancer patients in our institute.ResultsThe 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.ConclusionsThe 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.