Fluorescence-guided surgery, but not bright-light surgery, prevents local recurrence in a pancreatic cancer patient derived orthotopic xenograft (PDOX) model resistant to neoadjuvant chemotherapy (NAC)

Pancreatology. May-Jun 2015;15(3):295-301. doi: 10.1016/j.pan.2015.02.008. Epub 2015 Mar 7.

Abstract

Background: The aim of this study is to determine the efficacy of neoadjuvant chemotherapy (NAC) with gemcitabine (GEM) in combination with fluorescence-guided surgery (FGS) on a pancreatic cancer patient derived orthotopic xenograft (PDOX) model.

Methods: A PDOX model was established from a CEA-positive tumor from a patient who had undergone a pancreaticoduodenectomy for pancreatic adenocarcinoma. Mice were randomized to 4 groups: bright light surgery (BLS) only; BLS + NAC; FGS only; and FGS + NAC. An anti-CEA antibody conjugated to DyLight 650 was administered intravenously via the tail vein of mice with a pancreatic cancer PDOX 24 h before surgery.

Results: The PDOX was clearly labeled with fluorophore-conjugated anti-CEA antibody. Only one out of 8 mice had local recurrence in the FGS only group and zero out of 8 mice had local recurrence in the FGS + NAC which was significantly lower than BLS only or BLS + NAC mice, where local disease recurred in 6 out of 8 mice in each treatment group (p = 0.041 and p = 0.007, respectively). NAC did not significantly reduce recurrence rates when combined with either FGS or BLS.

Conclusion: These results indicate that FGS can significantly reduce local recurrence compared to BLS in pancreatic cancer resistant to NAC.

Keywords: CEA; Fluorescence-guided surgery; Neoadjuvant chemotherapy; PDOX; Pancreatic cancer; Patient derived orthotopic xenograft.

Publication types

  • Comparative Study
  • Evaluation Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / drug therapy
  • Adenocarcinoma / surgery*
  • Animals
  • Antimetabolites, Antineoplastic / therapeutic use*
  • Chemotherapy, Adjuvant
  • Deoxycytidine / analogs & derivatives*
  • Deoxycytidine / therapeutic use
  • Drug Resistance, Neoplasm
  • Fluorescent Dyes
  • Heterografts
  • Humans
  • Light
  • Mice
  • Mice, Inbred NOD
  • Mice, Nude
  • Neoadjuvant Therapy
  • Neoplasm Recurrence, Local / prevention & control*
  • Neoplasm Transplantation
  • Optical Imaging*
  • Pancreatectomy / methods*
  • Pancreatic Neoplasms / drug therapy
  • Pancreatic Neoplasms / surgery*
  • Random Allocation
  • Transplantation, Heterologous
  • Treatment Outcome

Substances

  • Antimetabolites, Antineoplastic
  • Fluorescent Dyes
  • Deoxycytidine
  • gemcitabine