Advertisement

International Journal of Clinical Oncology

, Volume 18, Issue 1, pp 1–9 | Cite as

Malignant ascites: pathophysiology and treatment

  • Emanuel CavazzoniEmail author
  • Walter Bugiantella
  • Luigina Graziosi
  • Maria Silvia Franceschini
  • Annibale Donini
Review Article

Abstract

Malignant ascites (MA) accompanies a variety of abdominal and extra-abdominal tumors. It is a primary cause of morbidity and raises several treatment challenges. MA has several symptoms, producing a significant reduction in the patient’s quality of life: loss of proteins and electrolyte disorders cause diffuse oedema, while the accumulation of abdominal fluid facilitates sepsis. Treatment options include a multitude of different procedures with limited efficacy and some degree of risk. A Pubmed, Medline, Embase, and Cochrane Library review of medical, interventional and surgical treatments of MA has been performed. Medical therapy, primarily paracentesis and diuretics, are first-line treatments in managing MA. Paracentesis is widely adopted but it is associated with significant patient discomfort and several risks. Diuretic therapy is effective at the very beginning of the disease but efficacy declines with tumor progression. Intraperitoneal chemotherapy, targeted therapy, immunotherapy and radioisotopes are promising medical options but their clinical application is not yet completely elucidated, and further investigations and trials are necessary. Peritoneal–venous shunts are rarely used due to high rates of early mortality and complications. Laparoscopy and hyperthermic intraperitoneal chemotherapy (HIPEC) have been proposed as palliative therapy. Literature on the use of laparoscopic HIPEC in MA includes only reports with small numbers of patients, all showing successful control of ascites. To date, none of the different options has been subjected to evidence-based clinical trials and there are no accepted guidelines for the management of MA.

Keywords

Malignant Ascites Peritoneal Carcinomatosis Palliation Paracentesis Intraperitoneal Hyperthermic Chemotherapy 

Abbreviations

MA

Malignant ascites

VEGF

Vascular endothelial growth factor

TNF

Tumor necrosis factor

MMP

Matrix metalloproteinases

IC

Intraperitoneal chemotherapy

HIPEC

Hyperthermic intraperitoneal chemotherapy

Notes

Conflict of interest

The authors declare that they have no conflict of interest.

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 (review)CrossRefGoogle Scholar
  2. 2.
    Saif MW, Siddiqui IA, Sohail MA (2009) Management of ascites due to gastrointestinal malignancy. Ann Saudi Med 29(5):369–377 (review)PubMedCrossRefGoogle Scholar
  3. 3.
    Keen A, Fitzgerald D, Bryant A et al (2010) Management of drainage for malignant ascites in gynaecological cancer. Cochrane Database Syst Rev (1):CD007794 (review)Google Scholar
  4. 4.
    Adam RA, Adam YG (2004) Malignant ascites: past, present, and future. J Am Coll Surg 198(6):999–1011 (review)PubMedCrossRefGoogle Scholar
  5. 5.
    Zebrowski BK, Liu W, Ramirez K et al (1999) Markedly elevated levels of vascular endothelial growth factor in malignant ascites. Ann Surg Oncol 6(4):373–378PubMedCrossRefGoogle Scholar
  6. 6.
    Brown PD (1995) Matrix metalloproteinase inhibitors: a novel class of anticancer agents. Adv Enzyme Regul 35:293–301PubMedCrossRefGoogle Scholar
  7. 7.
    Sharma S, Walsh D (1995) Management of symptomatic malignant ascites with diuretics: two case reports and a review of the literature. J Pain Symptom Manag 10(3):237–242 (review)CrossRefGoogle Scholar
  8. 8.
    Lee CW, Bociek G, Faught W (1998) A survey of practice in management of malignant ascites. J Pain Symptom Manag 16(2):96–101CrossRefGoogle Scholar
  9. 9.
    Pockros PJ, Esrason KT, Nguyen C et al (1992) Mobilization of malignant ascites with diuretics is dependent on ascitic fluid characteristics. Gastroenterology 103(4):1302–1306PubMedGoogle Scholar
  10. 10.
    Parsons SL, Watson SA, Steele RJ (1996) Malignant ascites. Br J Surg 83(1):6–14 (review)PubMedCrossRefGoogle Scholar
  11. 11.
    Covey AM (2005) Management of malignant pleural effusions and ascites. J Support Oncol 3(2):169–173, 176 (review)Google Scholar
  12. 12.
    McNamara P (2000) Paracentesis—an effective method of symptom control in the palliative care setting? Palliat Med 14(1):62–64PubMedCrossRefGoogle Scholar
  13. 13.
    Ginés P, Arroyo V, Quintero E et al (1987) Comparison of paracentesis and diuretics in the treatment of cirrhotics with tense ascites. Results of a randomized study. Gastroenterology 93(2):234–241PubMedGoogle Scholar
  14. 14.
    Ginès P, Titó L, Arroyo V et al (1988) Randomized comparative study of therapeutic paracentesis with and without intravenous albumin in cirrhosis. Gastroenterology 94(6):1493–1502PubMedGoogle Scholar
  15. 15.
    Salerno F, Badalamenti S, Incerti P et al (1987) Repeated paracentesis and i.v. albumin infusion to treat ‘tense’ ascites in cirrhotic patients. A safe alternative therapy. J Hepatol 5(1):102–108PubMedCrossRefGoogle Scholar
  16. 16.
    Quintero E, Ginés P, Arroyo V et al (1985) Paracentesis versus diuretics in the treatment of cirrhotics with tense ascites. Lancet 1(8429):611–612PubMedCrossRefGoogle Scholar
  17. 17.
    Fleming ND, Alvarez-Secord A, Von Gruenigen V et al (2009) Indwelling catheters for the management of refractory malignant ascites: a systematic literature overview and retrospective chart review. J Pain Symptom Manag 38(3):341–349 (review)CrossRefGoogle Scholar
  18. 18.
    Barnett TD, Rubins J (2002) Placement of a permanent tunneled peritoneal drainage catheter for palliation of malignant ascites: a simplified percutaneous approach. J Vasc Interv Radiol 13(4):379–383PubMedCrossRefGoogle Scholar
  19. 19.
    Rosenberg S, Courtney A, Nemcek AA et al (2004) Comparison of percutaneous management techniques for recurrent malignant ascites. J Vasc Interv Radiol 15:1129–1131PubMedCrossRefGoogle Scholar
  20. 20.
    Stokes LS (2007) Percutaneous management of malignant fluid collections. Semin Interv Radiol 24(4):398–408. doi: 10.1055/s-2007-992328 CrossRefGoogle Scholar
  21. 21.
    Becker G, Galandi D, Blum HE (2006) Malignant ascites: systematic review and guideline for treatment. Eur J Cancer 42(5):589–597 (review)PubMedCrossRefGoogle Scholar
  22. 22.
    Weisberger AS, Levine B, Storaasli JP (1955) Use of nitrogen mustard in treatment of serous effusions of neoplastic origin. J Am Med Assoc 159(18):1704–1707PubMedCrossRefGoogle Scholar
  23. 23.
    Appelqvist P, Silvo J, Salmela L et al (1982) On the treatment and prognosis of malignant ascites: is the survival time determined when the abdominal paracentesis is needed? J Surg Oncol 20(4):238–242PubMedCrossRefGoogle Scholar
  24. 24.
    Andersen AP, Brincker H (1968) Intracavitary thiotepa in malignant pleural and peritoneal effusions. Acta Radiol Ther Phys Biol 7(5):369–378PubMedCrossRefGoogle Scholar
  25. 25.
    Groesbeck HP, Cudmore JT (1962) Intracavitary thio-TEPA for malignant effusions. Am Surg 28:90–95PubMedGoogle Scholar
  26. 26.
    Jones AL, Trott P, Cunningham D et al (1994) A pilot study of intraperitoneal cisplatin in the management of gastric cancer. Ann Oncol 5(2):123–126PubMedCrossRefGoogle Scholar
  27. 27.
    Markman M, Kelsen D (1992) Efficacy of cisplatin-based intraperitoneal chemotherapy as treatment of malignant peritoneal mesothelioma. J Cancer Res Clin Oncol 118(7):547–550PubMedCrossRefGoogle Scholar
  28. 28.
    Speyer JL, Collins JM, Dedrick RL et al (1980) Phase I and pharmacological studies of 5-fluorouracil administered intraperitoneally. Cancer Res 40(3):567–572PubMedGoogle Scholar
  29. 29.
    Schilsky RL, Choi KE, Grayhack J et al (1990) Phase I clinical and pharmacologic study of intraperitoneal cisplatin and fluorouracil in patients with advanced intraabdominal cancer. J Clin Oncol 8(12):2054–2061PubMedGoogle Scholar
  30. 30.
    Kefford RF, Woods RL, Fox RM et al (1980) Intracavitary adriamycin nitrogen mustard and tetracycline in the control of malignant effusions: a randomized study. Med J Aust 2(8):447–448PubMedGoogle Scholar
  31. 31.
    Trotter JM, Stuart JFB, McBeth F et al (1979) The management of malignant effusions with bleomycin. Br J Cancer 40:310Google Scholar
  32. 32.
    Katano M, Torisu M (1982) Neutrophil-mediated tumor cell destruction in cancer ascites. Cancer 50(1):62–68PubMedCrossRefGoogle Scholar
  33. 33.
    Torisu M, Katano M, Kimura Y et al (1983) New approach to management of malignant ascites with a streptococcal preparation, OK-432. Improvement of host immunity and prolongation of survival. Surgery 93(3):357–364PubMedGoogle Scholar
  34. 34.
    Sherer DM, Eliakim R, Abulafia O (2000) The role of angiogenesis in the accumulation of peritoneal fluid in benign conditions and the development of malignant ascites in the female. Gynecol Obstet Invest 50(4):217–224 (review)PubMedCrossRefGoogle Scholar
  35. 35.
    Stoelcker B, Echtenacher B, Weich HA et al (2000) VEGF/Flk-1 interaction, a requirement for malignant ascites recurrence. J Interferon Cytokine Res 20(5):511–517PubMedCrossRefGoogle Scholar
  36. 36.
    Gebbia V, Russo A, Gebbia N et al (1991) Intracavitary beta-interferon for the management of pleural and/or abdominal effusions in patients with advanced cancer refractory to chemotherapy. In Vivo 5(6):579–581PubMedGoogle Scholar
  37. 37.
    Katano M, Morisaki T (1998) The past, the present and future of the OK-432 therapy for patients with malignant effusions. Anticancer Res 18(5D):3917–3925 (review)PubMedGoogle Scholar
  38. 38.
    Yamaguchi Y, Satoh Y, Miyahara E et al (1995) Locoregional immunotherapy of malignant ascites by intraperitoneal administration of OK-432 plus IL-2 in gastric cancer patients. Anticancer Res 15(5B):2201–2206PubMedGoogle Scholar
  39. 39.
    Ariel IM, Oropeza R, Pack GT (1966) Intracavitary administration of radioactive isotopes in the control of effusions due to cancer. Results in 267 patients. Cancer 19(8):1096–1102PubMedCrossRefGoogle Scholar
  40. 40.
    Jackson GL, Blosser NM (1981) Intracavitary chromic phosphate (32P) colloidal suspension therapy. Cancer 48(12):2596–2598PubMedCrossRefGoogle Scholar
  41. 41.
    Ward B, Mather S, Shepherd J et al (1988) The treatment of intraperitoneal malignant disease with monoclonal antibody guided 131I radiotherapy. Br J Cancer 58(5):658–662PubMedCrossRefGoogle Scholar
  42. 42.
    Buckman R, De Angelis C, Shaw P et al (1992) Intraperitoneal therapy of malignant ascites associated with carcinoma of ovary and breast using radioiodinated monoclonal antibody 2G3. Gynecol Oncol 47(1):102–109PubMedCrossRefGoogle Scholar
  43. 43.
    Kobold S, Hegewisch-Becker S, Oechsle K et al (2009) Intraperitoneal VEGF inhibition using bevacizumab: a potential approach for the symptomatic treatment of malignant ascites? Oncologist 14(12):1242–1251 (review)PubMedCrossRefGoogle Scholar
  44. 44.
    El-Shami K, Elsaid A, El-Kerm Y (2007) Open-label safety and efficacy pilot trial of intraperitoneal bevacizumab as palliative treatment in refractory malignant ascites. J Clin Oncol 25(18 Suppl):9043Google Scholar
  45. 45.
    Brown PD (1998) Matrix metalloproteinase inhibitors. Breast Cancer Res Treat 52(1–3):125–136 (review)PubMedCrossRefGoogle Scholar
  46. 46.
    Parsons SL, Watson SA, Steele RJ (1997) Phase I/II trial of batimastat, a matrix metalloproteinase inhibitor, in patients with malignant ascites. Eur J Surg Oncol 23(6):526–531PubMedCrossRefGoogle Scholar
  47. 47.
    Bramhall SR, Rosemurgy A, Brown PD, Marimastat Pancreatic Cancer Study Group et al (2001) Marimastat as first-line therapy for patients with unresectable pancreatic cancer: a randomized trial. J Clin Oncol 19(15):3447–3455PubMedGoogle Scholar
  48. 48.
    King J, Zhao J, Clingan P et al (2003) Randomised double blind placebo control study of adjuvant treatment with the metalloproteinase inhibitor, marimastat in patients with inoperable colorectal hepatic metastases: significant survival advantage in patients with musculoskeletal side-effects. Anticancer Res 23(1B):639–645PubMedGoogle Scholar
  49. 49.
    Seimetz D, Lindhofer H, Bokemeyer C (2010) Development and approval of the trifunctional antibody catumaxomab (anti-EpCAM × anti-CD3) as a targeted cancer immunotherapy. Cancer Treat Rev 36(6):458–467 (review)PubMedCrossRefGoogle Scholar
  50. 50.
    Burges A, Wimberger P, Kümper C et al (2007) Effective relief of malignant ascites in patients with advanced ovarian cancer by a trifunctional anti-EpCAM × anti-CD3 antibody: a phase I/II study. Clin Cancer Res 13(13):3899–3905PubMedCrossRefGoogle Scholar
  51. 51.
    Heiss MM, Murawa P, Koralewski P et al (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):2209–2221PubMedCrossRefGoogle Scholar
  52. 52.
    Garofalo A, Valle M, Garcia J et al (2006) Laparoscopic intraperitoneal hyperthermic chemotherapy for palliation of debilitating malignant ascites. Eur J Surg Oncol 32(6):682–685PubMedCrossRefGoogle Scholar
  53. 53.
    Knutsen A, Sielaff TD, Greeno E et al (2006) Staged laparoscopic infusion of hyperthermic intraperitoneal chemotherapy after cytoreductive surgery. J Gastrointest Surg 10(7):1038–1043PubMedCrossRefGoogle Scholar
  54. 54.
    Facchiano E, Scaringi S, Kianmanesh R et al (2008) Laparoscopic hyperthermic intraperitoneal chemotherapy (HIPEC) for the treatment of malignant ascites secondary to unresectable peritoneal carcinomatosis from advanced gastric cancer. Eur J Surg Oncol 34(2):154–158PubMedCrossRefGoogle Scholar
  55. 55.
    Valle M, Van der Speeten K, Garofalo A et al (2009) Laparoscopic hyperthermic intraperitoneal peroperative chemotherapy (HIPEC) in the management of refractory malignant ascites: a multi-institutional retrospective analysis in 52 patients. J Surg Oncol 100(4):331–334PubMedCrossRefGoogle Scholar
  56. 56.
    Graziosi L, Bugiantella W, Cavazzoni E et al (2009) Laparoscopic intraperitoneal hyperthermic perfusion in palliation of malignant ascites. Case report. G Chir 30(5):237–239PubMedGoogle Scholar
  57. 57.
    Gesson-Paute A, Ferron G, Thomas F et al (2008) Pharmacokinetics of oxaliplatin during open versus laparoscopically assisted heated intraoperative intraperitoneal chemotherapy (HIPEC): an experimental study. Ann Surg Oncol 15(1):339–344PubMedCrossRefGoogle Scholar
  58. 58.
    Chua TC, Yan TD, Saxena A et al (2009) Should the treatment of peritoneal carcinomatosis by cytoreductive surgery and hyperthermic intraperitoneal chemotherapy still be regarded as a highly morbid procedure? A systematic review of morbidity and mortality. Ann Surg 249(6):900–907 (review)PubMedCrossRefGoogle Scholar
  59. 59.
    Deraco M, Baratti D, Laterza B et al (2011) Advanced cytoreduction as surgical standard of care and hyperthermic intraperitoneal chemotherapy as promising treatment in epithelial ovarian cancer. Eur J Surg Oncol 37(1):4–9 (review)PubMedCrossRefGoogle Scholar
  60. 60.
    Fagotti A, Paris I, Grimolizzi F et al (2009) Secondary cytoreduction plus oxaliplatin-based HIPEC in platinum-sensitive recurrent ovarian cancer patients: a pilot study. Gynecol Oncol 113(3):335–340PubMedCrossRefGoogle Scholar
  61. 61.
    Kim JH, Lee JM, Ryu KS et al (2010) Consolidation hyperthermic intraperitoneal chemotherapy using paclitaxel in patients with epithelial ovarian cancer. J Surg Oncol 101(2):149–155PubMedGoogle Scholar
  62. 62.
    Kobold S, Hegewisch-Becker S, Oechsle K et al (2009) Intraperitoneal VEGF inhibition using bevacizumab: a potential approach for the symptomatic treatment of malignant ascites? Oncologist 14(12):1242–1251 (review)PubMedCrossRefGoogle Scholar
  63. 63.
    Elias D, Gilly F, Quenet F et al (2010) Pseudomyxoma peritonei: a French multicentric study of 301 patients treated with cytoreductive surgery and intraperitoneal chemotherapy. Eur J Surg Oncol 36(5):456–462PubMedCrossRefGoogle Scholar
  64. 64.
    Yan TD, Deraco M, Baratti D et al (2009) Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for malignant peritoneal mesothelioma: multi-institutional experience. J Clin Oncol 27(36):6237–6242PubMedCrossRefGoogle Scholar
  65. 65.
    Imamoto H, Oba K, Sakamoto J et al (2011) Assessing clinical benefit response in the treatment of gastric malignant ascites with non-measurable lesions: a multicenter phase II trial of paclitaxel for malignant ascites secondary to advanced/recurrent gastric cancer. Gastric Cancer 14(1):81–90PubMedCrossRefGoogle Scholar
  66. 66.
    Oriuchi N, Nakajima T, Mochiki E et al (2005) A new, accurate and conventional five-point method for quantitative evaluation of ascites using plain computed tomography in cancer patients. Jpn J Clin Oncol 35(7):386–390PubMedCrossRefGoogle Scholar
  67. 67.
    Bellati F, Napoletano C, Gasparri ML et al (2011) Monoclonal antibodies in gynecological cancer: a critical point of view. Clin Dev Immunol 2011:890758PubMedCrossRefGoogle Scholar
  68. 68.
    Hall M, Rustin G (2011) Recurrent ovarian cancer: when and how to treat. Curr Oncol Rep 13(6):459–471 (review)PubMedCrossRefGoogle Scholar
  69. 69.
    Tappenden P, Jones R, Paisley S et al (2007) Systematic review and economic evaluation of bevacizumab and cetuximab for the treatment of metastatic colorectal cancer. Health Technol Assess 11(12):1–128, III–IV (review)Google Scholar
  70. 70.
    Garrett CR, Eng C (2011) Cetuximab in the treatment of patients with colorectal cancer. Expert Opin Biol Ther 11(7):937–949 (review)PubMedCrossRefGoogle Scholar
  71. 71.
    Dotan E, Meropol NJ, Burtness B et al (2012) A phase II study of capecitabine, oxaliplatin, and cetuximab with or without bevacizumab as frontline therapy for metastatic colorectal cancer. A Fox Chase Extramural Research Study. J Gastrointest Cancer [Epub ahead of print]Google Scholar

Copyright information

© Japan Society of Clinical Oncology 2012

Authors and Affiliations

  • Emanuel Cavazzoni
    • 1
    Email author
  • Walter Bugiantella
    • 1
  • Luigina Graziosi
    • 1
  • Maria Silvia Franceschini
    • 2
  • Annibale Donini
    • 1
  1. 1.Section of General and Emergency Surgery, Department of Surgery, “Santa Maria della Misericordia” HospitalUniversity of Perugia, School of MedicinePerugiaItaly
  2. 2.Department of Radiology, “Santa Maria della Misericordia” HospitalUniversity of Perugia, School of MedicinePerugiaItaly

Personalised recommendations