Renal and hepatic toxicities after pressurized intraperitoneal aerosol chemotherapy (PIPAC)

Ann Surg Oncol. 2013 Jul;20(7):2311-6. doi: 10.1245/s10434-012-2840-2. Epub 2013 Feb 3.


Background: Both in animal models and in human patients, pressurized intraperitoneal aerosol chemotherapy (PIPAC) has been shown to improve local bioavailability of chemotherapy in peritoneal nodules, as compared with conventional peritoneal lavage. Pharmacokinetic studies show a low drug concentration in peripheral venous blood. However, hepatic and renal toxicities induced by delivering chemotherapeutic drugs into the abdomen as a pressurized aerosol have not yet been investigated.

Methods: Liver and renal function as well as toxicity parameters were monitored after eight PIPAC applications with doxorubicin (1.5 mg/m(2) body surface) and cisplatin (7.5 mg/m(2) body surface) in three end-stage patients suffering therapy-resistant peritoneal carcinomatosis. PIPAC was repeated at 4-week intervals (three times in two patients, twice in one patient). Peripheral venous blood was collected preoperatively and then daily until the 5th postoperative day, and sent to the hospital's clinical chemistry laboratory. Statistical analysis was performed by analysis of variance (ANOVA).

Results: Gamma-glutamyltransferase was significantly elevated (p < 0.05) in the early postoperative phase. Glutamic oxaloacetic transaminase [aspartate aminotransferase], glutamic pyruvic transaminase [alanine aminotransferase], and bilirubin levels were not influenced by the procedure. Quick-test remained normal. Serum creatinine levels were not altered.

Conclusions: Under the above conditions, PIPAC did not induce clinically relevant liver cytotoxicity. Liver metabolism and function were not altered. Renal function remained within the normal range. No cumulative toxicity was observed after repeated PIPAC. PIPAC appears to be associated with very limited hepatic and renal toxicity, which might be a significant advantage over other administration routes.

MeSH terms

  • Acute Kidney Injury / blood
  • Acute Kidney Injury / chemically induced*
  • Adult
  • Aerosols / administration & dosage
  • Aerosols / adverse effects
  • Aged
  • Alanine Transaminase / blood
  • Analysis of Variance
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage*
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects*
  • Aspartate Aminotransferases / blood
  • Bilirubin / blood
  • Carcinoma / drug therapy*
  • Chemical and Drug Induced Liver Injury / blood
  • Chemical and Drug Induced Liver Injury / etiology*
  • Cisplatin / administration & dosage
  • Creatinine / blood
  • Doxorubicin / administration & dosage
  • Female
  • Humans
  • Laparoscopy
  • Male
  • Middle Aged
  • Peritoneal Cavity
  • Peritoneal Neoplasms / drug therapy*
  • Pressure
  • gamma-Glutamyltransferase / blood


  • Aerosols
  • Doxorubicin
  • Creatinine
  • gamma-Glutamyltransferase
  • Aspartate Aminotransferases
  • Alanine Transaminase
  • Cisplatin
  • Bilirubin