Comparison Between the Internal and External Pressure Filtration Method of Cell-Free and Concentrated Ascites Reinfusion Therapy Using the Same Cancerous Ascites

Cell-free and concentrated ascites reinfusion therapy (CART) is one of the treatments for refractory ascites. Symptoms caused by ascites may be relieved and the urinary volume could be increased by CART 1-4. Clogging of the filter is one of the major problems associated with CART. Modification of the circuit design or washing of the membrane has been used to avoid clogging 5. CART is classified based on the filtration method and the driving force. The filtration method includes internal pressure filtration method (internal method) and external pressure filtration method (external method), and the driving force includes negative pressure, pump, and gravity. Few studies comparing the different methods using the same ascites have been reported 6. In this study, we performed CART by the internal and external methods using the same cancerous ascites and compared the circuit pressure and the solute recovery rate.

PATIENTS AND METHODS

Patients with intractable cancerous ascites with indication for CART were recruited from February 2017 to April 2018. Sixteen CART sessions on 11 patients were registered. The AHF–MO ascetic filtration filter (Asahi Kasei Medical, Tokyo, Japan) was used for filtration, and Plasauto LC (Asahi Kasei Medical, Tokyo, Japan) was used as the blood purification device. The quantity of ascites obtained from each patient was divided into two, and each half was processed using the external or internal method at a treatment rate of 50 mL/min (Fig. 1). A case in which the circuit pressure reached 100 mmHg or more in either or both methods was defined as a “rise group.” A case in which the circuit pressure did not reach 100 mmHg in any method was defined as a “nonrise group.” When the circuit pressure reached 150 mmHg, only the relevant filtration method was stopped. If the circuit pressure did not reach 150 mmHg, both methods were terminated when the treatment of the total amount of ascites was completed. We examined the circuit pressure and solute recovery rate. The solute recovery rate (%) was calculated by the following equation:

Data analyses were performed using the Statistical Package for Social Science (spss), version 25.0 for Windows (SPSS, Chicago, IL, USA). Continuous data were expressed as median and interquartile range. Continuous data were analyzed by Mann–Whitney’s U-test or Wilcoxon’s signed-rank test, whereas categorical data were analyzed by chi-square test. P value less than 0.05 was considered significant.

Our study was approved by the ethics committee of Fujita Health University School of Medicine (UMIN registration number UMIN000025382).

RESULTS

Sieving coefficient of solute

Figure 2 shows the sieving coefficient of solutes obtained based on the results for albumin, IL-6, IgG, IgA, and IgM. There were differences in the sieving coefficient between the internal and external methods as molecular weight increased.

Changes in circuit pressure

Figure 3 shows the flow diagram according to the circuit pressure. The circuit pressure rose above 100 mmHg in eight of 16 cases. For four of eight cases, the circuit pressure rose earlier in the internal method than in the external method. For the remaining four cases, the circuit pressure rose earlier in the external method than in the internal method. When the circuit pressure in the internal method rose above 100 mmHg first, the circuit pressure in the external method also rose above 100 mmHg subsequently. On the other hand, when the pressure in the external method rose above 100 mmHg first, only one case from the internal method showed a rise in circuit pressure above 100 mmHg subsequently. In the remaining three cases, the rise in the circuit pressure was below 100 mmHg.

DISCUSSION

Here, CART by internal and external filtration pressure methods using the same cancerous ascites was performed. Previously, Hata et al. compared the two filtration methods using the same ascites from hepatic cirrhosis patients 6. This is the first report comparing internal method and external method using the same cancerous ascites. No difference was found in the rate of circuit pressure rise, while the recovery rate of solutes was different between the two methods. The recovery rates of haptoglobin and immunoglobulin were significantly higher for the internal method than for the external method. As shown in Figure 2, the pore distribution is different between the internal method and the external method, despite the fact that the same membrane was used. This might be related to the difference in the recovery rate. The recovery rate of α₁-antitrypsin by the internal method was significantly lower than that by the external method. α₁-Antitrypsin is a low molecular weight protein, with a molecular weight of 51 KD and a serine protease inhibitor 7. The levels of α₁-antitrypsin might decrease in the filtrated ascites because it bound to serine protease. If α₁-antitrypsin bound to neutrophil elastase 8, one of the serine proteases, the levels of elastase in the filtered ascites would have decreased. Examining the levels of elastase is the focus of our future studies. In both methods, the levels of FDP were lower and soluble fibrin monomer complex were higher in the filtrated ascites than in the original ascites. Upregulation of coagulation system and downregulation of fibrinolysis might be triggered during the filtration process. Another possibility is that a portion of the FDP was captured by the fibrin clots.

We set the cut-off value of rise group as 100 mmHg because the filtration pressure is recommended to be maintained under 100 mmHg in the case of bloody ascites according to the attached document. In a comparison between the rise group and nonrise group, the levels of acute phase proteins such as haptoglobin, α₁-antitrypsin, and the inflammatory cytokine, IL-6 were higher in the rise group than in the nonrise group. As a result of the inflammatory reaction, these acute phase proteins increase, leading to a high total protein concentration, which might be related to clogging and a rise in circuit pressure. As for the coagulation fibrinolysis system, the levels of FDP were higher and fibrin monomer complex were lower in the rise group. Elevated FDP might reflect elevated levels of fibrinogen and fibrin, which cause clot formation. Other markers such as fibrinogen, thrombin antithrombin complex, and plasmin-alpha2-plasmininhibitor-complex will be needed to evaluate the coagulation fibrinolysis system correctly. Although heparin was not used in this study, heparin was added to the collection bag at a frequency of 26.6% in postmarketing surveillance 1. Since the coagulation system is suppressed by adding heparin, the increase in the fibrin monomer complex might be suppressed.

CONCLUSIONS

From this study, either method will lead to similar effects in terms of the circuit pressure rise and albumin recovery rate. The internal pressure method might be preferable under conditions where γ-globulin is decreased, while the external method might be preferable under conditions where α₁-antitrypsin is decreased.