Supportive Care in Cancer

, Volume 26, Issue 5, pp 1489–1497 | Cite as

Efficacy and safety of reinfusion of concentrated ascitic fluid for malignant ascites: a concept-proof study

  • Rumi Hanada
  • Naosuke Yokomichi
  • Chihiro Kato
  • Kazumi Miki
  • Sachiko Oyama
  • Tatsuya Morita
  • Ryoko Kawahara
Original Article

Abstract

Purpose

Malignant ascites is one of the symptoms causing discomfort in advanced cancer patients. Cell-free and concentrated ascites reinfusion therapy (CART) is one treatment modality, but controlled trials are limited. The primary aim of this study was to explore the efficacy and safety of CART, as well as their predictors, to obtain data for planning a further controlled trial.

Methods

This was a single center retrospective cohort study in patients with refractory malignant ascites. Consecutive adult patients who underwent CART were enrolled. The primary endpoints were the time to next paracentesis and seven patient-reported symptoms (e.g., abdominal pain and distension). The secondary endpoints were adverse events, laboratory findings, and physical findings.

Results

A total of 104 CART procedures for 51 patients were analyzed. The median time to next paracentesis was 27 days (95% CI, 21–35). Intensities of all seven symptoms were significantly improved after CART (p < 0.0001 for all symptoms). Grade 3 hypotension occurred during one procedure, and mild fever occurred in 5%. Total protein, albumin, and estimated glomerular filtration rate were significantly increased. Hemorrhagic ascites, ascites white blood cell count, serum total protein, and lymphocyte percentages were the independent predictors of the time to next paracentesis.

Conclusion

The effects of reinfusion of concentrated ascitic fluid may be maintained for 1 month, being potentially longer than that of total paracentesis alone. This study had no comparison groups and examined the short-term effect. A randomized controlled study to compare the long-term effects of total paracentesis alone vs. CART is necessary.

Keywords

Ascites Malignancy Paracentesis Filtration Palliative care 

Notes

Compliance with ethical standards

The study was approved by the institutional review board of Nissay General Hospital.

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

520_2017_3980_MOESM1_ESM.docx (148 kb)
ESM 1 (DOCX 147 kb)

References

  1. 1.
    Smith EM, Jayson GC (2003) The current and future management of malignant ascites. Clin Oncol (R Coll Radiol) 15(2):59–72.  https://doi.org/10.1053/clon.2002.0135 CrossRefGoogle Scholar
  2. 2.
    Keen J (2015) Jaundice, ascites, and encephalopathy. In: Cherny NI, Fallon MT, Kaasa S, Portenoy RK, Currow DC (eds) Oxford textbook of palliative medicine, 5th edn. Oxford University Press, New York, pp 686–701Google Scholar
  3. 3.
    Becker G, Galandi D, Blum HE (2006) Malignant ascites: systematic review and guideline for treatment. Eur J Cancer 42(5):589–597.  https://doi.org/10.1016/j.ejca.2005.11.018 CrossRefPubMedGoogle Scholar
  4. 4.
    Cavazzoni E, Bugiantella W, Graziosi L, Franceschini MS, Donini A (2013) Malignant ascites: pathophysiology and treatment. Int J Clin Oncol 18(1):1–9.  https://doi.org/10.1007/s10147-012-0396-6 CrossRefPubMedGoogle Scholar
  5. 5.
    Runyon BA (1994) Care of patients with ascites. N Engl J Med 330(5):337–342.  https://doi.org/10.1056/NEJM199402033300508 CrossRefPubMedGoogle Scholar
  6. 6.
    Levy VG, Hecht Y, Georgacopoulos H, Hadchouel P, Touboul JP, Sausse A et al (1971) Drying of cirrhotic ascites by continuous intravenous reinjection of concentrated ascitic fluid. Ann Med Interne (Paris) 122(11):1075–1085Google Scholar
  7. 7.
    Parbhoo SP, Ajdukiewicz A, Sherlock S (1974) Treatment of ascites by continuous ultrafiltration and reinfusion of protein concentrate. Lancet 1(7864):949–952CrossRefPubMedGoogle Scholar
  8. 8.
    Smart HL, Triger DR (1990) A randomised prospective trial comparing daily paracentesis and intravenous albumin with recirculation in diuretic refractory ascites. J Hepatol 10(2):191–197.  https://doi.org/10.1016/0168-8278(90)90051-R CrossRefPubMedGoogle Scholar
  9. 9.
    Bruno S, Borzio M, Romagnoni M, Battezzati PM, Rossi S, Chiesa A, Podda M (1992) Comparison of spontaneous ascites filtration and reinfusion with total paracentesis with intravenous albumin infusion in cirrhotic patients with tense ascites. BMJ 304(6843):1655–1658.  https://doi.org/10.1136/bmj.304.6843.1655 CrossRefPubMedCentralPubMedGoogle Scholar
  10. 10.
    Graziotto A, Rossaro L, Inturri P, Salvagnini M (1997) Reinfusion of concentrated ascitic fluid versus total paracentesis. A randomized prospective trial. Dig Dis Sci 42(8):1708–1714.  https://doi.org/10.1023/A:1018865516168 CrossRefPubMedGoogle Scholar
  11. 11.
    Landini S, Coli U, Fracasso A, Morachiello P, Righetto F, Scanferla F, Genchi R, Bazzato G (1985) Spontaneous ascites filtration and reinfusion (SAFR) in cirrhotic patients. Int J Artif Organs 8(5):277–280PubMedGoogle Scholar
  12. 12.
    Villeneuve JP, Thuot C, Marleau D, Joly JG, Huet PM, Viallet A (1977) Treatment of resistant ascites by continuous ultrafiltration—reinfusion of ascitic fluid. Can Med Assoc J 117(11):1296–1298PubMedCentralPubMedGoogle Scholar
  13. 13.
    Inoue N, Yamazaki Z, Oda T, Sugiura M, Wada T (1977) Treatment of intractable ascites by continuous reinfusion of the sterilized, cell-free and concentrated ascitic fluid. Trans Am Soc Artif Intern Organs 23:699–702CrossRefPubMedGoogle Scholar
  14. 14.
    Ito T, Hanafusa N, Iwase S, Noiri E, Nangaku M, Nakagawa K, Miyagawa K (2015) Effects of cell-free and concentrated ascites reinfusion therapy (CART) on symptom relief of malignancy-related ascites. Int J Clin Oncol 20(3):623–628.  https://doi.org/10.1007/s10147-014-0750-y CrossRefPubMedGoogle Scholar
  15. 15.
    Ito T, Hanafusa N, Fukui M, Yamamoto H, Watanabe Y, Noiri E, Iwase S, Miyagawa K, Fujita T, Nangaku M (2014) Single center experience of cell-free and concentrated ascites reinfusion therapy in malignancy related ascites. Ther Apher Dial 18(1):87–92.  https://doi.org/10.1111/1744-9987.12049 CrossRefPubMedGoogle Scholar
  16. 16.
    Yamaguchi H, Kitayama J, Emoto S, Ishigami H, Ito T, Hanafusa N, Watanabe T (2015) Cell-free and concentrated ascites reinfusion therapy (CART) for management of massive malignant ascites in gastric cancer patients with peritoneal metastasis treated with intravenous and intraperitoneal paclitaxel with oral S-1. Eur J Surg Oncol 41(7):875–880.  https://doi.org/10.1016/j.ejso.2015.04.013 CrossRefPubMedGoogle Scholar
  17. 17.
    Katoh S, Kojima T, Itoh K, Yoneyama S, Ida K, Nakaji S (1997) Usefulness of a nonmachinery based system for the reinfusion of cell-free and concentrated autogenous ascitic fluid. Artif Organs 21(12):1232–1238CrossRefPubMedGoogle Scholar
  18. 18.
    Katoh S, Tatsukawa H, Kondoh M, Inoue M, Ida K, Miyagawa F (1991) Prevention of the febrile reaction occurring on reinfusion of cell-free and concentrated autogenous ascites. Jpn J Med 30(4):311–317.  https://doi.org/10.2169/internalmedicine1962.30.311 CrossRefPubMedGoogle Scholar
  19. 19.
    Orimi S, Mizuno K, Narahara M, Umakosi H, Kaihara M, Hashimoto M (2011) A study of appropriate flow rate settings for cell-free and concentrated ascites reinfusion therapy and change of cytokine concentrations in ascites. Ther Apher Dial 15(4):411–414.  https://doi.org/10.1111/j.1744-9987.2011.00973.x CrossRefPubMedGoogle Scholar
  20. 20.
    Maeda O, Ando T, Ishiguro K, Watanabe O, Miyahara R, Nakamura M, Funasaka K, Kazuhiro F, Ando Y, Goto H (2014) Safety of repeated cell-free and concentrated ascites reinfusion therapy for malignant ascites from gastrointestinal cancer. Mol Clin Oncol 2(6):1103–1106.  https://doi.org/10.3892/mco.2014.335 CrossRefPubMedCentralPubMedGoogle Scholar
  21. 21.
    Japanese CSG, Matsusaki K, Ohta K, Yoshizawa A, Gyoda Y (2011) Novel cell-free and concentrated ascites reinfusion therapy (KM-CART) for refractory ascites associated with cancerous peritonitis: its effect and future perspectives. Int J Clin Oncol 16:395–400CrossRefGoogle Scholar
  22. 22.
    Heiss MM, Murawa P, Koralewski P, Kutarska E, Kolesnik OO, Ivanchenko VV, Dudnichenko AS, Aleknaviciene B, Razbadauskas A, Gore M, Ganea-Motan E, Ciuleanu T, Wimberger P, Schmittel A, Schmalfeldt B, Burges A, Bokemeyer C, Lindhofer H, Lahr A, Parsons SL (2010) The trifunctional antibody catumaxomab for the treatment of malignant ascites due to epithelial cancer: results of a prospective randomized phase II/III trial. Int J Cancer 127(9):2209–2221.  https://doi.org/10.1002/ijc.25423 CrossRefPubMedCentralPubMedGoogle Scholar
  23. 23.
    Jatoi A, Nieva JJ, Qin R, Loprinzi CL, Wos EJ, Novotny PJ, Moore DF Jr, Mowat RB, Bechar N, Pajon ER Jr, Hartmann LC (2012) A pilot study of long-acting octreotide for symptomatic malignant ascites. Oncology 82(6):315–320.  https://doi.org/10.1159/000337246 CrossRefPubMedCentralPubMedGoogle Scholar
  24. 24.
    Ross GJ, Kessler HB, Clair MR, Gatenby RA, Hartz WH, Ross LV (1989) Sonographically guided paracentesis for palliation of symptomatic malignant ascites. AJR Am J Roentgenol 153(6):1309–1311.  https://doi.org/10.2214/ajr.153.6.1309 CrossRefPubMedGoogle Scholar
  25. 25.
    Matsuo S, Imai E, Horio M, Yasuda Y, Tomita K, Nitta K, Yamagata K, Tomino Y, Yokoyama H, Hishida A, Collaborators developing the Japanese equation for estimated GFR (2009) Revised equations for estimated GFR from serum creatinine in Japan. Am J Kidney Dis 53(6):982–992.  https://doi.org/10.1053/j.ajkd.2008.12.034 CrossRefPubMedGoogle Scholar
  26. 26.
    Morita T, Tsunoda J, Inoue S, Chihara S (1999) The palliative prognostic index: a scoring system for survival prediction of terminally ill cancer patients. Support Care Cancer 7(3):128–133.  https://doi.org/10.1007/s005200050242 CrossRefPubMedGoogle Scholar
  27. 27.
    Yamaguchi T, Mori T, Takahashi K, Matsumoto H, Miyamoto H, Kato T (2008) A new classification system for liver metastases from colorectal cancer in Japanese multicenter analysis. Hepato-Gastroenterology 55(81):173–178PubMedGoogle Scholar
  28. 28.
    Anthony T, Baron T, Mercadante S, Green S, Chi D, Cunningham J, Herbst A, Smart E, Krouse RS (2007) Report of the clinical protocol committee: development of randomized trials for malignant bowel obstruction. J Pain Symptom Manag 34(1):S49–S59.  https://doi.org/10.1016/j.jpainsymman.2007.04.011 CrossRefGoogle Scholar
  29. 29.
    Kanda Y (2013) Investigation of the freely available easy-to-use software ‘EZR’ for medical statistics. Bone Marrow Transplant 48(3):452–458.  https://doi.org/10.1038/bmt.2012.244 CrossRefPubMedGoogle Scholar
  30. 30.
    Easson AM, Bezjak A, Ross S, Wright JG (2007) The ability of existing questionnaires to measure symptom change after paracentesis for symptomatic ascites. Ann Surg Oncol 14(8):2348–2357.  https://doi.org/10.1245/s10434-007-9370-3 CrossRefPubMedGoogle Scholar
  31. 31.
    Runyon BA, Hoefs JC, Morgan TR (1988) Ascitic fluid analysis in malignancy-related ascites. Hepatology 8(5):1104–1109.  https://doi.org/10.1002/hep.1840080521 CrossRefPubMedGoogle Scholar
  32. 32.
    Urrunaga NH, Singal AG, Cuthbert JA, Rockey DC (2013) Hemorrhagic ascites. Clinical presentation and outcomes in patients with cirrhosis. J Hepatol 58(6):1113–1118.  https://doi.org/10.1016/j.jhep.2013.01.015 CrossRefPubMedCentralPubMedGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2017

Authors and Affiliations

  1. 1.Department of Anesthesiology and Palliative CareNissay HospitalOsakaJapan
  2. 2.Seirei HospiceSeirei Mikatahara General HospitalShizuokaJapan
  3. 3.Clinical Engineering Laboratory, Division of Central Clinical Research LaboratoryNissay HospitalOsakaJapan
  4. 4.Department of NursingNissay HospitalOsakaJapan
  5. 5.Department of Palliative and Supportive Care, Palliative Care Team, and Seirei HospiceSeirei Mikatahara General HospitalHamamatsuJapan
  6. 6.Department of Palliative Care, Hoshigaoka Medical CenterOsakaJapan

Personalised recommendations