Pressurized intraperitoneal aerosol chemotherapy (PIPAC) might increase the risk of anastomotic leakage compared to HIPEC: an experimental study

Surg Endosc. 2020 Jul;34(7):2939-2946. doi: 10.1007/s00464-019-07076-3. Epub 2019 Aug 27.

Abstract

Background: Pressurized intraperitoneal aerosol chemotherapy (PIPAC) and hyperthermic intraperitoneal chemotherapy (HIPEC) are technics proposed to treat patients with peritoneal carcinomatosis, in different settings. There is some concern about an over-risk of anastomotic leakage (AL) with PIPAC jeopardizing a combination with cytoreductive surgery. This study used a healthy swine model to compare the postoperative AL rate between PIPAC and HIPEC with digestive resection and to analyze macrocirculation and microcirculation parameters.

Methods: Segmental colonic resection with a handsewn anastomosis was performed on 16 healthy pigs; 8 pigs had a PIPAC procedure with 7.5 mg/m2 cisplatin (PIPAC group), and 8 pigs had a closed HIPEC procedure with 70 mg/m2 cisplatin and 42 °C as the target intraperitoneal temperature (HIPEC group). Pigs were kept alive for 8 days, then sacrificed and autopsied to look for AL, which was defined as local abscess or digestive fluid leakage when pressure was applied to the anastomosis. Food intake, weight, and core temperature were monitored postoperatively. Macrocirculation (heart rate, systolic blood pressure) and microcirculation parameters (percentage of perfused vessels, perfused vessels density, DeBacker score) were evaluated intraoperatively at five timepoints. Results were compared between pigs with AL and those without.

Results: The HIPEC group had no AL, but 3 of 8 pigs (37.5%) had AL in the PIPAC group (p = 0.20). Heart rate and core temperature showed perioperative increases in the HIPEC group. Intraoperatively, heart rate was higher in the HIPEC group at the two last timepoints (123 vs. 93 bpm, p = 0.031, and 110 vs. 85 bpm, p = 0.010, at timepoints 3 and 4, respectively). Other macrocirculatory and microcirculatory parameters showed no significant differences.

Conclusion: In this healthy swine model, PIPAC might have increased AL incidence compared to HIPEC. This potential over-risk did not seem to be related to changes in the microcirculation. PIPAC should probably not be used with digestive resection and should be avoided in cases of perioperative serosal injury.

Keywords: Fistula; HIPEC; Macrocirculation; Microcirculation; PIPAC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aerosols / administration & dosage
  • Anastomotic Leak / etiology*
  • Animals
  • Anti-Bacterial Agents / pharmacology
  • Blood Pressure / drug effects
  • Cisplatin / administration & dosage
  • Colon / surgery*
  • Cytoreduction Surgical Procedures / adverse effects*
  • Cytoreduction Surgical Procedures / methods
  • Heart Rate / drug effects
  • Hyperthermic Intraperitoneal Chemotherapy / adverse effects*
  • Hyperthermic Intraperitoneal Chemotherapy / methods
  • Male
  • Microcirculation
  • Peritoneal Neoplasms / drug therapy*
  • Swine
  • Treatment Outcome

Substances

  • Aerosols
  • Anti-Bacterial Agents
  • Cisplatin