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

Objectives: 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. Methods: 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). Results: We identified nine cases and 16 sessions. In the flush+rinse group, the median amount of washing solution used per membrane washing was 259 mL per cycle, whereas it was 54 mL 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). Conclusions: 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.

BACKGROUND/AIM: 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. PATIENTS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Successful treatment of systemic AL amyloidosis with autologous hematopoietic stem cell transplantation combined with cell-free and concentrated ascites reinfusion therapy.

Key Clinical Message: AL patients develop the unique toxicities of fluid retention and non-cardiogenic pulmonary edema during the course of stem cell mobilization. We propose mobilization with CART as effective and safe treatment for AL patients with refractory anasarca. Abstract: We describe a 63-year-old male with systemic immunoglobulin light chain (AL) amyloidosis with cardiac, renal, and liver involvement. After four courses of CyBorD, mobilization with G-CSF at 10 µg/kg was initiated and CART was simultaneously performed for fluid retention. No adverse events were observed during collection or reinfusion. Anasarca gradually disappeared and he underwent autologous hematopoietic stem cell transplantation. The complete remission of AL amyloidosis has been maintained, and the condition of the patient has remained stable for 7 years. We propose mobilization with CART as an effective and safe treatment option for AL patients with refractory anasarca.

Changes in Coagulation and Fibrinolytic Factors in Patients With Cirrhotic Refractory Ascites Undergoing Cell-free and Concentrated Ascites Reinfusion Therapy: A Retrospective Observational Study in Japan.

BACKGROUND/AIM: 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. PATIENTS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Cell-free and concentrated ascites reinfusion therapy for refractory massive cardiac ascites in an adult with single ventricle haemodynamics: a case report.

Background: Cardiac ascites is a classical finding of right-sided heart failure, mainly caused by tricuspid valve disease and constrictive pericarditis. Refractory cardiac ascites, defined as ascites that is uncontrollable with any medication, including conventional diuretics and selective vasopressin V2 receptor antagonists, is a rare but challenging entity. Although cell-free and concentrated ascites reinfusion therapy (CART) is a therapeutic option for refractory ascites in patients with liver cirrhosis and malignancy, its efficacy in cardiac ascites has never been reported. We herein report a case of CART for refractory cardiac ascites in a patient with complex adult congenital heart disease (ACHD). Case summary: A 43-year-old Japanese female with a history of ACHD involving single ventricle haemodynamics presented with refractory massive cardiac ascites due to progressive heart failure. Because conventional therapy using diuretics could not control her cardiac ascites, abdominal paracentesis was frequently required, resulting in hypoproteinaemia. Therefore, CART was initiated once per month in addition to conventional therapies, which enabled the prevention of hypoproteinaemia and further hospitalizations except to undergo CART. In addition, it helped improve her quality of life without any complications for 6 years until she died from cardiogenic cerebral infarction at the age of 49 years. Discussion: This case demonstrated that CART can be safely performed in patients with complex ACHD and refractory cardiac ascites due to advanced heart failure. Thus, CART may improve refractory cardiac ascites as effectively as massive ascites caused by liver cirrhosis and malignancy and lead to an improvement in the patients' quality of life.

[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.

Feasibility of a fast-track randomized controlled trial of cell-free and concentrated ascites reinfusion therapy for patients with refractory malignant ascites.

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.

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

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.

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

BACKGROUND: Malignancy-related ascites (MRA) is one of the symptoms causing discomfort in advanced cancer patients. Cell-free and concentrated ascites reinfusion therapy (CART) is one of the palliative treatments widely conducted in Japan only. METHODS: A systematic review following a meta-analysis of CART was performed. The efficiency and adverse events were evaluated. RESULTS: A total of 2567 patients and 6013 procedures of CART were identified in this study. The mean volume of MRA collected was 4.29 (95% confidence interval (CI) 3.47-5.11) L, and the volume reinfused after concentrating was 0.49 (95% CI 0.39-0.60) L. A total of 86.1 (95% CI 77.1-95.2) g protein and 42.9 (95% CI 36.0-50.0) g albumin was reinfused. The mean time to the next paracentesis was 20.7 (95% CI 15.6-25.8) days. The body weight was reduced by 3.38 (95% CI 1.90-4.86; p < 0.01) kg, and abdominal circumference was reduced by 7.86 (95% CI 6.58-9.14; p < 0.001) cm. Serum albumin increased an average of 0.14 (95% CI -0.01-0.28; p = 0.07) mg/dL the day after CART. Abdominal distension, dyspnea, and fatigue were alleviated by 6.0 (95% CI 5.59-6.51), 2.66 (95% CI 2.05-3.28), and 2.64 (95% CI 1.86-3.42) points using a numerical rating scale system ranging from 0 to 10. Overall, 17% (95% CI 0.03-0.31%) of patients had improved performance status after CART. Significant body temperature elevation was observed, at an average of 0.4 °C (95% CI 0.18-0.62 °C). CONCLUSIONS: CART might be a safe and effective palliative therapy in MRA and further clinical trials are necessary.

Safety and efficacy of cell-free and concentrated ascites reinfusion therapy against cirrhotic ascites in comparison with malignancy-related ascites.

BACKGROUND AND AIM: Cell-free and concentrated ascites reinfusion therapy (CART) has been performed against cirrhotic ascites, one of the most common complications seen in patients with decompensated cirrhosis. The aim of this study is to investigate its safety and efficacy, and differences in clinical profiles from CART against malignancy-related ascites with different pathological background. METHODS: The present investigation involved a sub-analysis of data obtained from a prospective observational study of CART performed at 22 centers. The condition of each procedure, therapeutic options, laboratory data, performance status, dietary intake, and abdominal circumference of participants were analyzed. Clinical parameters were compared between before and after CART, with or without albumin infusion, and also primary diseases including cirrhosis and malignant disease. RESULTS: Between January 2014 and January 2015, a total of 48 and 275 CART procedures were performed in patients with cirrhosis and malignancies. In cirrhotic patients, serum albumin concentration increased significantly in groups both with and without concomitant albumin infusion (P = 0.002 and P = 0.023), and no significant difference in CART interval was seen between these groups (P = 0.393). CART interval was not significantly different between cirrhosis and malignancy groups (P = 0.334). Dietary intake significantly improved after CART in both groups (P = 0.043 and P < 0.001). Adverse events were with no clinical significance as observed in patients with malignancies. CONCLUSIONS: Cell-free and concentrated ascites reinfusion therapy was performed safely and effectively in patients with ascites related to decompensated cirrhosis and offers the potential efficacy to maintain plasma colloid osmotic pressure after paracentesis as well as in patients with malignancy.

Evaluation of the performance, operability, and safety of Plasauto µ, a new type of machine for cell-free and concentrated ascites reinfusion therapy, in a postmarketing clinical study.

Cell-free and concentrated ascites reinfusion therapy (CART) is performed by collecting the ascites from the patient, followed by filtration and concentration. Thereafter, concentrated cell-free ascites is reinfused into the patient intravenously. The new type of machine, Plasauto µ, for managing the process of CART was launched onto the market. We have evaluated the machine through postmarketing clinical study in 17 patients with malignant ascites. The amounts of original and concentrated ascites were 3673 ± 1920 g and 439 ± 228 g, respectively. Recovery rates were acceptable regarding values of total protein, albumin, and IgG that were 55.6% ± 17.3%, 60.2% ± 20.8%, and 58.2% ± 20.5%, respectively. Recovery rates were positively associated with amounts of original ascites and negatively associated with total protein concentration. No adverse events related to the machine were observed. The new type of machine showed preferable performance in processing malignant ascites.

Large-volume cell-free and concentrated ascites reinfusion therapy improves venous flow in patients with liver cirrhosis.

PURPOSE: Hemodynamic change after total paracentesis was investigated because it might lead to various complications. Although cell-free and concentrated ascites reinfusion therapy (CART) is safer and more effective than total paracentesis in theory, hemodynamic change after CART has been never reported. And previous studies did not mention hemodynamics of the venous system. METHODS: We investigated the hemodynamic change, including that of the venous system, before and after CART using color Doppler ultrasonography and fast Fourier transform analysis. Twenty-eight patients with tensive cirrhotic ascites underwent ultrasonography the day before and after total volume CART. The diameter and velocity of the main, right, and left portal vein; inferior vena cava (IVC); and right renal vein were measured using ultrasonography. RESULTS: A total of 11.8 ± 4.4 L of ascites (range 3.6-20.9 L) was filtered and concentrated to 0.85 ± 0.40 L (range 0.36-1.50 L). The diameter of the IVC increased from median 13.5 ± 5.4 mm (range 4-25 mm) to 18.5 ± 4.1 mm (range 7-29 mm) (p = 0.007). The diameter of the right segmental renal vein significantly increased after KM-CART [from 5.0 ± 1.0 (4-8) mm to 7.0 ± 2.0 (3-10) mm] (p = 0.011). Hemodynamic change of the portal venous system was not significant. The time to the next CART in patients with an IVC diameter ≥ 20 mm and < 20 mm was 86 days and 20.5 days (p = 0.035), respectively. CONCLUSION: Tensive ascites results in venous congestion in patients with cirrhotic ascites. CART improved venous flow, but it did not change the hemodynamics of the portal venous system.

Clinical usefulness of cell-free and concentrated ascites reinfusion therapy (CART) in combination with chemotherapy for malignant ascites: a post-marketing surveillance study.

BACKGROUND: Cell-free and concentrated ascites reinfusion therapy (CART) has been suggested to be able to treat malignant ascites more safely and effectively with chemotherapy because of its ability to retain serum protein and albumin. Although the characteristics of cancer types and CART and the clinical implications of combination therapy with antitumor agents are becoming widespread, there are limited reports on its efficacy and complications. METHODS: In this prospective observational national post-marketing study, 128 patients with malignancies received 300 CART sessions at 22 centers. After excluding other malignancies, the patients were divided into four groups: gynecological malignancies with chemotherapy (GYC+; 18 cases and 36 times) and without chemotherapy (GYC-; 35 cases and 52 times), and gastrointestinal malignancies with chemotherapy (GIC+; 8 cases and 16 times) and without chemotherapy (20 cases and 58 times). RESULTS: There were significant reductions in the body weight in all groups and significant reductions in abdominal circumference and significant improvements in the diet and Eastern Cooperative Oncology Group performance status only in the GYC+ group. The total serum protein and albumin increased significantly in all groups, except for the GIC+ group, before and after CART. There was no significant difference in the presence or absence of antitumor medication. CONCLUSION: With CART, there were differences in the improvement of the clinical symptoms between malignancy groups. The combination of CART and antineoplastic agents may be as safe as CART alone in cases of exudative malignant ascites.

Encapsulating peritoneal sclerosis caused by cell-free and concentrated ascites reinfusion therapy: a case report.

BACKGROUND: Encapsulating peritoneal sclerosis (EPS) is a rare condition in which the small intestine is covered by an inflammatory fibrocollagenous membrane; the exact etiology of EPS is unclear. Herein, we report the case of our patient who underwent hemodialysis and cell-free and concentrated ascites reinfusion therapy (CART) and was diagnosed with EPS. CASE PRESENTATION: A 64-year-old Japanese man visited our emergency department with a chief complaint of abdominal pain. He had a medical history of cirrhosis due to hepatitis C for 25 years. He had undergone partial resection of the small intestine 2 years earlier for an incarcerated hernia. One year earlier, he experienced renal failure due to hepatorenal syndrome and started hemodialysis three times a week and CART twice a month. Physical examination of the abdominal wall revealed a lack of peristalsis of the intestinal tract and strong tenderness on palpation. Because hernia of the small intestine was found on computed tomography, we suspected strangulation ileus, requiring emergency operation. When the abdomen was opened, the entire small intestine was found to be wrapped in a fibrous membrane and constricted by it. The patient was diagnosed with EPS; hence, during surgery, the fibrous membrane was excised, resulting in decompression of the intestinal tract and subsequent recovery. CONCLUSIONS: EPS is thought to be related to various elements, but no case of EPS induced by CART has been reported to date. EPS should be considered in the differential diagnosis of small bowel obstruction in patients undergoing CART for refractory ascites.

Quality of life assessment of cell-free and concentrated ascites reinfusion therapy during initial treatment for advanced ovarian cancer: A prospective cohort study.

AIM: Cell-free and concentrated ascites reinfusion therapy (CART) is applied to relieve symptoms in patients with malignant ascites. We performed a prospective cohort study to evaluate the efficacy and safety of CART performed on patients with advanced ovarian and peritoneal cancers with massive ascites during the initial treatment. METHODS: From April 2018 to July 2020, CART was performed during the initial treatment of 31 patients with advanced ovarian and peritoneal cancers with cancerous ascites. Patient characteristics and clinical information before and after CART were collected. We performed quality of life assessment using the Japanese version of the M.D. Anderson Symptom Inventory (MDASI-J) 24 h before and after CART. RESULTS: CART was performed 38 times in 24 patients before or during neoadjuvant chemotherapy and 11 times in 11 patients prior to surgery. Four patients underwent CART before primary surgery and before and/or during chemotherapy. Grade 1-2 fever was observed in 18 of 31 cases (58%), and all were controllable by nonsteroidal anti-inflammatory drugs. CART did not adversely affect the main treatment, chemotherapy, or surgery. CART significantly improved the MDASI-J symptom and interference scores within 24 h after the procedure. The symptom and interference scores decreased from 2.4 to 1.8 and from 4.8 to 3.0, respectively. CONCLUSIONS: CART can be safely performed and is useful for symptom relief and improvement of general condition prior to initial surgery and during initial chemotherapy in ovarian and peritoneal cancers. Performing CART at the time of initial treatment may facilitate initiation of the main treatment.

Suppression of inflammation during cell-free concentrated ascites reinfusion therapy using a blood purification device.

In recent years, cell-free concentrated ascites reinfusion therapy has been used to treat patients with malignant ascites. However, concentrated ascites reinfusion therapy involves enrichment and reinfusion of useful proteins and inflammatory cytokines. Therefore, fever is a primary side effect and significant problem for patients with ascites. We removed IL-6, an inflammatory cytokine, by mixing malignant ascites and the hexadecyl group adsorbent from a ß2 -microglobulin-adsorbing column (Lixelle S-15). As a result, the hexadecyl group adsorbent did not adsorb the albumin of malignant ascites but adsorbed 43% of IL-6. To investigate the effect of the hexadecyl group adsorbent on hepatocytes, the adsorbed ascites was added to a human hepatoma cell line (HepG2), and the gene expression levels of albumin and serum amyloid A protein were examined. After absorption, ascites showed significantly suppressed serum amyloid A protein expression and significantly increased albumin gene expression compared to before adsorption. Our results suggest that incorporation of Lixelle to filter and concentrate malignant ascites can suppress inflammatory responses and reduce the inhibition of albumin synthesis in the liver after reinfusion.

Development of a novel automatic ascites filtration and concentration equipment with multi-ring-type roller pump units for cell-free and concentrated ascites reinfusion therapy.

Cell-free and concentrated ascites reinfusion therapy (CART) is an effective therapy for refractory ascites. However, CART is difficult to perform as ascites filtration and concentration is a complicated procedure. Moreover, the procedure requires the constant assistance of a clinical engineer or/and the use of an expensive equipment for the multi-purpose blood processing. Therefore, we developed a CART specialized equipment (mobility CART [M-CART]) that could be used safely with various safety measures and automatic functions such as automatic washing of clogged filtration filter and self-regulation of the concentration ratio. Downsizing, lightning of the weight, and automatic processing in M-CART required the use of newly developed multi-ring-type roller pump units. This equipment was approved under Japanese regulations in 2018. In performing 41 sessions of CART (for malignant ascites, 22 sessions; and hepatic ascites, 19 sessions) using this equipment in 17 patients, no serious adverse event occurred. An average of 4494 g of ascites was collected and the total amount of ascites was processed in all the sessions without any trouble. The mean weight of the processed ascites was 560 g and the mean concentration ratio was 8.0. The ascites were processed at a flow rate of 50 mL/min. The mean ascites processing time was 112.5 minutes and a 106.5-minutes (95.2%) ascites processing was performed automatically. The operator responded to alarms or support information 3.2 times on average (3.1 minutes, 2.1% of ascites processing time). Human errors related to ascites processing were detected by M-CART at 0.4 times per session on average and were appropriately addressed by the operator. The frequencies of automatic washing of clogged filtration filter and self-regulation of the concentration ratio were 31.7% and 53.7%, respectively. The mean recovery rates (recovery dose) of protein, albumin, and immunoglobulin G were 72.9%, 72.9%, and 71.2% (65.9 g, 34.9 g, and 13.2 g), respectively. Steroids were administered in 92.7% of the sessions to prevent fever and the mean increase in body temperature was 0.53°C. M-CART is a compact and lightweight automatic CART specialized equipment that can safely and easily process a large quantity of ascites without the constant assistance of an operator.

Ascitic IL-10 Concentration Predicts Prognosis of Patients Undergoing Cell-Free and Concentrated Ascites Reinfusion Therapy.

Cell-free and concentrated ascites reinfusion therapy (CART) is now attracting rising attention as one of the strategies against cancer-related malignant ascites in Japan. Several studies report the safety, effectiveness, and complications of CART applied to patients with malignancies. However, its mechanism reflecting these effects still remains unclear. We evaluated concentration of inflammatory cytokines including interleukin (IL)-1ß, IL-6, IL-8, IL-12, tumor necrosis factor (TNF)-α, and immunosuppressive cytokine IL-10 in ascites before CART procedures. We investigated their impacts on survival. IL-1ß, IL-6, IL-8, TNF-α, and IL-10 were detected in ascites of the patients undergoing CART. Significant body temperature elevation, one potential complication of CART, was observed among the patients although it was not clinically important. There were no significant correlations between changes in body temperature and the concentration of IL-6, IL-8, and IL-10. The presence of IL-10 in ascites significantly related to longer survival after the first session of CART procedures. However, we observed no other clinically important correlation between cytokine concentrations and changes in WBC and CRP. Concentration of inflammatory cytokines in ascites did not relate to body temperature change, the chief complication of CART. Surprisingly, the presence of IL-10 in ascites related to longer survival after CART. Immunological environment of cancer-related ascites may reflect the outcome of CART and improve survival in those with malignancy.

Cell-free and Concentrated Ascites Reinfusion Therapy for Refractory Ascites in Cirrhosis in Post-marketing Surveillance and the Role of Tolvaptan.

Objective Ascites becomes refractory to diuretics in cirrhotic patients, who then require repeated large-volume paracentesis or cell-free and concentrated ascites reinfusion therapy (CART). The objective of this study was to confirm the safety and efficacy of CART, evaluate the actual situations with respect to the prescription of diuretics and determine the role of diuretics after the introduction of CART. Patients and Methods We recruited 34 cirrhotic patients who received CART with concomitant diuretics using furosemide (76.2%), spironolactone (48.5%), thiazide (4.0%) and tolvaptan (53.5%) from a post-marketing surveillance of CART. Results CART improved the tested clinical indices, i.e., body weight, abdominal circumference, performance status, dietary intake, total protein and albumin. The intervals of CART sessions were significantly prolonged in patients who received tolvaptan (mean, 22.5 days) compared to those not receiving tolvaptan (mean, 10.8 days) (p<0.001). The drop-out rate was significantly decreased in patients receiving tolvaptan compared to those not receiving tolvaptan when drop-out was defined as paracentesis (p<0.05). Conclusion We confirmed that CART is an effective treatment for refractory ascites occurring in cirrhotic patients. The administration of tolvaptan in combination with CART leads to a significantly reduced rate of ascites accumulation.