Cytoreductive Surgery Plus Hyperthermic Intraperitoneal Chemotherapy Improves Survival of Gastric Cancer with Peritoneal Carcinomatosis: Evidence from an Experimental Study

Overview

Journal J Transl Med

Publisher Biomed Central

Specialties Biomedical Engineering
General Medicine

Date 2011 May 10

PMID 21548973

Citations 17

Authors

Li Tang

Lie-Jun Mei

Xiao-Jun Yang

Chao-Qun Huang

Yun-Feng Zhou

Yutaka Yonemura

Yan Li

Affiliations

Soon will be listed here.

Abstract

Background: Cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) has been considered as a promising treatment modality for gastric cancer with peritoneal carcinomatosis (PC). However, there have also been many debates regarding the efficacy and safety of this new approach. Results from experimental animal model study could help provide reliable information. This study was to investigate the safety and efficacy of CRS + HIPEC to treat gastric cancer with PC in a rabbit model.

Methods: VX2 tumor cells were injected into the gastric submucosa of 42 male New Zealand rabbits using a laparotomic implantation technique, to construct rabbit model of gastric cancer with PC. The rabbits were randomized into control group (n = 14), CRS alone group (n = 14) and CRS + HIPEC group (n = 14). The control group was observed for natural course of disease progression. Treatments were started on day 9 after tumor cells inoculation, including maximal removal of tumor nodules in CRS alone group, and maximal CRS plus heperthermic intraperitoneal chemoperfusion with docetaxel (10 mg/rabbit) and carboplatin (40 mg/rabbit) at 42.0 ± 0.5°C for 30 min in CRS + HIPEC group. The primary endpoint was overall survival (OS). The secondary endpoints were body weight, biochemistry, major organ functions and serious adverse events (SAE).

Results: Rabbit model of gastric cancer with PC was successfully established in all animals. The clinicopathological features of the model were similar to human gastric PC. The median OS was 24.0 d (95% confidence interval 21.8 - 26.2 d ) in the control group, 25.0 d (95% CI 21.3 - 28.7 d ) in CRS group, and 40.0 d (95% CI 34.6 - 45.4 d ) in CRS + HIPEC group (P = 0.00, log rank test). Compared with CRS only or control group, CRS + HIPEC could extend the OS by at least 15 d (60%). At the baseline, on the day of surgery and on day 8 after surgery, the peripheral blood cells counts, liver and kidney functions, and biochemistry parameters were all comparable. SAE occurred in 0 animal in control group, 2 animals in CRS alone group including 1 animal death due to anesthesia overdose and another death due to postoperative hemorrhage, and 3 animals in CRS + HIPEC group including 1 animal death due to anesthesia overdose, and 2 animal deaths due to diarrhea 23 and 27 d after operation.

Conclusions: In this rabbit model of gastric cancer with PC, CRS alone could not bring benefit while CRS + HIPEC with docetaxel and carboplatin could significantly prolong the survival with acceptable safety.

Citing Articles

Molecular Typing of Gastric Cancer Based on Invasion-Related Genes and Prognosis-Related Features.

Guo H, Tang H, Zhao Y, Zhao Q, Hou X, Ren L Front Oncol. 2022; 12:848163.

PMID: 35719914 PMC: 9203697. DOI: 10.3389/fonc.2022.848163.

Preclinical In Vivo-Models to Investigate HIPEC; Current Methodologies and Challenges.

Helderman R, Loke D, Tanis P, Tuynman J, Ceelen W, de Hingh I Cancers (Basel). 2021; 13(14).

PMID: 34298644 PMC: 8303745. DOI: 10.3390/cancers13143430.

Prevention of Venous Thromboembolism After Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy: Development of a Physiotherapy Program.

Li X, Peng K, Ji Z, Yu Y, Liu G, Li Y Clin Appl Thromb Hemost. 2019; 25:1076029619890415.

PMID: 31775523 PMC: 7019383. DOI: 10.1177/1076029619890415.

Animal models of colorectal peritoneal metastasis.

Gremonprez F, Willaert W, Ceelen W Pleura Peritoneum. 2019; 1(1):23-43.

PMID: 30911606 PMC: 6386381. DOI: 10.1515/pp-2016-0006.

Peritoneal Carcinomatosis Diagnosis and Treatment in China: Focusing on Training and Collaboration.

Li X, Ji Z, Li Y Indian J Surg Oncol. 2019; 10(Suppl 1):12-18.

PMID: 30886487 PMC: 6397119. DOI: 10.1007/s13193-019-00890-0.

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