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

Autor: Chan CH; Department of Surgery, Massachusetts General Hospital, Boston, MA, USA. carloshfchan@gmail.com.; Department of Surgery, University of Iowa Carver College of Medicine, Iowa City, IA, USA. carloshfchan@gmail.com., Liesenfeld LF; Department of Surgery, Massachusetts General Hospital, Boston, MA, USA., Ferreiro-Neira I; Department of Surgery, Massachusetts General Hospital, Boston, MA, USA., Cusack JC Jr; Department of Surgery, Massachusetts General Hospital, Boston, MA, USA. jcusack@mgh.harvard.edu.
Jazyk: angličtina
Zdroj: Annals of surgical oncology [Ann Surg Oncol] 2017 Apr; Vol. 24 (4), pp. 931-938. Date of Electronic Publication: 2016 Dec 02.
DOI: 10.1245/s10434-016-5690-5
Abstrakt: 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.
Databáze: MEDLINE