Evaluation of a new histological grading system for assessing the response to chemotherapy of peritoneal metastases from colorectal cancer: A mouse model study

Abdelkader Taibi; Rea Lo Dico; Rachid Kaci; Anne Laure Naneix; Brice Malgras; Muriel Mathonnet; Marc Pocard

doi:10.1016/j.ejso.2019.09.008

Evaluation of a new histological grading system for assessing the response to chemotherapy of peritoneal metastases from colorectal cancer: A mouse model study

Eur J Surg Oncol. 2020 Jan;46(1):160-165. doi: 10.1016/j.ejso.2019.09.008. Epub 2019 Sep 12.

Authors

Abdelkader Taibi¹, Rea Lo Dico², Rachid Kaci³, Anne Laure Naneix⁴, Brice Malgras⁵, Muriel Mathonnet⁶, Marc Pocard⁷

Affiliations

¹ Department of Digestive Surgery, Dupuytren university Hospital, Avenue Martin Luther King, F-87000, Limoges, France; CNRS, XLIM, UMR 7252, Limoges University, 123 avenue Albert Thomas, F-87060, France; Université de Paris, CAP Paris-Tech, INSERM U1275, 49 boulevard de la Chapelle, F-75475, Paris cedex 10, France.
² Université de Paris, CAP Paris-Tech, INSERM U1275, 49 boulevard de la Chapelle, F-75475, Paris cedex 10, France; Department of Oncologic and Digestive Surgery, AP-HP, Hospital Lariboisière, 2 rue Ambroise Paré, F-75475, Paris cedex, 10, France.
³ Université de Paris, CAP Paris-Tech, INSERM U1275, 49 boulevard de la Chapelle, F-75475, Paris cedex 10, France; Department of Pathology, AP-HP, Hospital Lariboisière, 2 rue Ambroise Paré, F-75475, Paris cedex,10, France.
⁴ Department of Pathology, AP-HP, Hospital Lariboisière, 2 rue Ambroise Paré, F-75475, Paris cedex,10, France.
⁵ Université de Paris, CAP Paris-Tech, INSERM U1275, 49 boulevard de la Chapelle, F-75475, Paris cedex 10, France; Department of Digestive Surgery, Begin Military Teaching Hospital, 69 Avenue de Paris, F-94160 Saint-Mandé, France.
⁶ Department of Digestive Surgery, Dupuytren university Hospital, Avenue Martin Luther King, F-87000, Limoges, France.
⁷ Université de Paris, CAP Paris-Tech, INSERM U1275, 49 boulevard de la Chapelle, F-75475, Paris cedex 10, France; Department of Oncologic and Digestive Surgery, AP-HP, Hospital Lariboisière, 2 rue Ambroise Paré, F-75475, Paris cedex, 10, France. Electronic address: marc.pocard@gmail.com.

PMID: 31540756
DOI: 10.1016/j.ejso.2019.09.008

Abstract

This experimental study evaluated the histological response of peritoneal metastases (PM) from colorectal cancer (CRC) after preoperative systemic chemotherapy (pCT). The results demonstrated that the Peritoneal Regression Grade Score could be used in medical practice.

Aim: The aim was to evaluate the histological criteria used by the tumour regression grade (TRG) and Peritoneal Regression Grade Score (PRGS) for determining the response to chemotherapy (CT), in a mouse model of peritoneal metastases (PM) from colorectal cancer (CRC).

Methods: Twenty immunocompetent BALB/c mice were randomized into four groups at day (D) 10 after intraperitoneal (ip) injection with bioluminescent CRC tumour cells (CT26-luc). A histology before treatment group was obtained by sacrifice on D10; the other groups all received one of the following ip treatments over 15 days: 5% glucose (control, G5); 5-fluorouracil (5FU, 0.03 mg/g); or 5FU with oxaliplatin (Ox, 0.006 mg/g). The histological response (HR) was analysed by comparing the histology of PM before and after treatment, using both scores: TRG and PRGS.

Results: All mice showed limited PM as visualised by bioluminescence and confirmed at the time of sacrifice in the histology before treatment group. The mean peritoneal carcinomatosis index (PCI) was = 8 [6-10], The rate of complete HR was significantly higher in the Ox-5FU group (83.3%) than 5FU group (0%) and G5 group (0%) (p = 0.016). Fibrosis was present only in CT-treated groups (p = 0.05). PCI, ascites volume and haemorrhagic ascites were significantly higher in the G5 group than CT groups (p < 0.05).

Conclusions: The TRG score can be used in practice when we want to compare the HR between the primary tumour and the PMs. The PRGS is a good measure of HR and is correlated with the efficacy of CT.

Keywords: Chemotherapy; Colorectal cancer; Histological response; Mice model; PRGS; TRG.

Publication types

Evaluation Study

MeSH terms

Animals
Antineoplastic Combined Chemotherapy Protocols / pharmacology*
Colorectal Neoplasms / pathology*
Disease Models, Animal
Fluorouracil / pharmacology
Luminescent Measurements
Mice
Mice, Inbred BALB C
Neoplasm Grading / methods*
Oxaliplatin / pharmacology
Peritoneal Neoplasms / drug therapy*
Peritoneal Neoplasms / secondary*

Substances

Oxaliplatin
Fluorouracil