title: Renal and hepatic toxicities after pressurized intraperitoneal aerosol chemotherapy (PIPAC).
abstract: 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.
authors: Department of Surgery, Marienhospital Herne, Ruhr University Bochum, Bochum, Germany.
authors: Ana
authors: A
authors: Blanco
authors: Urs
authors: U
authors: Giger-Pabst
authors: Wiebke
authors: W
authors: Solass
authors: Jürgen
authors: J
authors: Zieren
authors: Marc A
authors: MA
authors: Reymond
mesh_terms: D058186:Acute Kidney Injury / Q000097:blood / Q000139:chemically induced*; D000328:Adult; D000336:Aerosols / Q000008:administration & dosage / Q000009:adverse effects; D000368:Aged; D000410:Alanine Transaminase / Q000097:blood; D000704:Analysis of Variance; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects*; D001219:Aspartate Aminotransferases / Q000097:blood; D001663:Bilirubin / Q000097:blood; D002277:Carcinoma / Q000188:drug therapy*; D056486:Chemical and Drug Induced Liver Injury / Q000097:blood / Q000209:etiology*; D002945:Cisplatin / Q000008:administration & dosage; D003404:Creatinine / Q000097:blood; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D006801:Humans; D010535:Laparoscopy; D008297:Male; D008875:Middle Aged; D010529:Peritoneal Cavity; D010534:Peritoneal Neoplasms / Q000188:drug therapy*; D011312:Pressure; D005723:gamma-Glutamyltransferase / Q000097:blood
chemical_list: D000336:Aerosols; D004317:Doxorubicin; D003404:Creatinine; D005723:gamma-Glutamyltransferase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D002945:Cisplatin; D001663:Bilirubin
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