Murine Models of Intraperitoneal Perfusion for Disseminated Colorectal Cancer

J Surg Res. 2019 Jan:233:310-322. doi: 10.1016/j.jss.2018.07.063. Epub 2018 Sep 5.

Abstract

Background: Reproduction of the perfusion used in therapy (hyperthermic intraperitoneal chemotherapy) procedures preclinically represents a valuable asset for investigating new therapeutic agents that may improve patient outcomes. This article provides technical descriptions of our execution of closed and open "coliseum" abdominal perfusion techniques in a mouse model of peritoneal carcinomatosis of colorectal cancer.

Materials and methods: BALB/c mice presenting with disseminated colorectal cancer (CT26-luciferin cells) underwent 30-min perfusions mimicking either the closed perfusion or the coliseum perfusion technique. Disease burden was monitored by bioluminescence signaling using an in vivo imaging system. Perfusion circuits consisted of single inflow lines with either a single or dual outflow line.

Results: Twelve mice presenting with disseminated disease underwent the closed perfusion technique. Surgical complications included perfusate leakage and organ constriction/suction into the outflow line(s). Nine mice underwent the coliseum perfusion technique with surgical debulking, using bipolar cauterization to remove tumors attached to the peritoneum. All mice survived the coliseum perfusion with limited intraoperative complications.

Conclusions: Fewer intraoperative complications were experienced with our coliseum perfusion technique than the closed perfusion. The methods described here can be used as a guideline for developing future perfusion murine models for investigating perfusion models useful for delivery of chemotherapy or other tumor-sensitization agents, including selective targeted agents, nanoparticles, and heat.

Keywords: Colorectal cancer; Intraabdominal perfusion; Murine model; Peritoneal carcinomatosis.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Antineoplastic Agents / administration & dosage*
  • Cell Line, Tumor / transplantation
  • Chemotherapy, Cancer, Regional Perfusion / adverse effects
  • Chemotherapy, Cancer, Regional Perfusion / instrumentation
  • Chemotherapy, Cancer, Regional Perfusion / methods*
  • Colorectal Neoplasms / pathology
  • Colorectal Neoplasms / therapy*
  • Combined Modality Therapy / adverse effects
  • Combined Modality Therapy / instrumentation
  • Combined Modality Therapy / methods
  • Disease Models, Animal
  • Female
  • Humans
  • Hyperthermia, Induced / adverse effects
  • Hyperthermia, Induced / instrumentation
  • Hyperthermia, Induced / methods*
  • Intraoperative Complications / epidemiology
  • Intraoperative Complications / etiology
  • Mice
  • Mice, Inbred BALB C
  • Peritoneal Neoplasms / secondary
  • Peritoneal Neoplasms / therapy*
  • Treatment Outcome

Substances

  • Antineoplastic Agents