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Annals of Surgical Oncology
Published in: Annals of Surgical Oncology 4/2017

01-04-2017 | Gastrointestinal Oncology

Preclinical Evaluation of Cathepsin-Based Fluorescent Imaging System for Cytoreductive Surgery

Authors: Carlos H. F. Chan, MD, PhD, Lukas F. Liesenfeld, MD, Isabel Ferreiro-Neira, PhD, James C. Cusack Jr., MD

Published in: Annals of Surgical Oncology | Issue 4/2017

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Abstract

Background

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) is a treatment option for peritoneal surface malignancies. The ability to detect microscopic foci of peritoneal metastasis intraoperatively may ensure the completeness of cytoreduction. In this study, we evaluated the suitability of a hand-held cathepsin-based fluorescent imaging system for intraoperative detection of appendiceal and colorectal peritoneal metastasis.

Methods

Peritoneal tumors and normal peritoneal tissues were collected from patients with appendiceal and colorectal peritoneal metastasis. Expression of different cathepsins (CTS-B, -D, -F, -G, -K, -L, -O, and -S) was determined by quantitative RT-PCR and immunohistochemistry. The hand-held cathepsin-based fluorescent imaging system was used to detect peritoneal xenografts derived from human colon cancer cells (HT29, LoVo and HCT116) in nu/nu mice.

Results

While the expression levels of CTS-B, -D, -L, and -S could be higher in peritoneal tumors than normal peritoneum with a median (range) of 6.1 (2.9–25.8), 2.0 (1.0–15.8), 1.4 (0.8–7.0), and 2.1 (1.6–13.9) folds by quantitative RT-PCR, respectively, CTS-B was consistently the major contributor of the overall cathepsin expression in appendiceal and colonic peritoneal tumors, including adenocarcinomas and low-grade appendiceal mucinous neoplasms. Using peritoneal xenograft mouse models, small barely visible colonic peritoneal tumors (<2.5 mm in maximum diameter) could be detected by the hand-held cathepsin-based fluorescent imaging system.

Conclusions

Because cathepsin expression is higher in peritoneal tumors than underlying peritoneum, the hand-held cathepsin-based fluorescent imaging system could be useful for intraoperative detection of microscopic peritoneal metastasis during CRS-HIPEC and clinical trial is warranted.
Appendix
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Metadata
Title
Preclinical Evaluation of Cathepsin-Based Fluorescent Imaging System for Cytoreductive Surgery
Authors
Carlos H. F. Chan, MD, PhD
Lukas F. Liesenfeld, MD
Isabel Ferreiro-Neira, PhD
James C. Cusack Jr., MD
Publication date
01-04-2017
Publisher
Springer International Publishing
Published in
Annals of Surgical Oncology / Issue 4/2017
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-016-5690-5

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