The impact of surgical extent and sex on the hepatic metastasis of colon cancer

Abstract

Purpose Extensive oncological surgeries were previously suggested to increase cancer recurrence rates. We herein studied the impact of different surgical procedures and sex on colorectal cancer liver metastasis, employing several tumor-inoculation approaches in BALB/c mice. Methods Experimental hepatic metastases of the syngeneic CT26 colorectal cancer line were induced either by intra-portal inoculation or intrasplenic inoculation, employing different tumor loads. Following intrasplenic inoculation, the entire spleen or an injected hemispleen were removed. Additionally, the magnitude of the surgical trauma accompanying the injection procedure was manipulated. Results Increasing the surgical trauma by adding laparotomy or extending the length of the surgery and hypothermia did not significantly affect the number of liver metastases or liver weight for any of the injection methods and tumor loads. The development of metastasis was significantly greater in males than in females under all conditions studied – a difference not explained by the direct effects of sex hormones on in vitro CT26 proliferation or vitality. Conclusion Concurring with less controlled clinical observations, the surgical extensiveness did not significantly affect CT26 hepatic metastasis, potentially due to a ceiling effect of the surgical trauma on the metastatic process. The sexual dimorphism observed for the CT26 metastasis should be investigated in the context of surgical stress and considering anti-CT26 immunoreactivity.

Reducing liver metastases of colon cancer in the context of extensive and minor surgeries through β-adrenoceptors blockade and COX2 inhibition

“…No significant differences in metastatic development were evident between mild and extensive procedures, and the drug treatment was similarly efficacious in both conditions. In previous studies we also found similar developmental courses of experimental liver metastases in this tumor model employing surgical procedures of different extent (Sorski et al, 2014). Clinical studies comparing laparotomy to laparoscopy in colorectal cancer patients also did not show significant differences in long-term cancer outcomes (Jayne et al, 2010), despite many short-term advantages to minimal invasive surgeries (Biondi et al, 2013), as was also evident herein by lower levels of corticosterone in animals subjected to small incision.…”

“…We have already reported in a previous study that females exhibit markedly fewer CT26 metastases than males, irrespective of (i) different injection procedures used, (ii) the load of CT26 cells challenge, and (iii) the magnitude of the surgical procedure (Sorski et al, 2014). We speculated that, among other mechanisms, males may be more prone to the impact of surgery while being administered with tumor cells, thus exhibiting more metastases.…”

“…To this end, syngeneic CT26 colon carcinoma cells were administered to BALB/c mice in the context of surgery via the portal vein or through the spleen (Sorski et al, 2014), and hepatic metastases were studied. Thus, this approach models tumor colonization of a prominent metastatic site of CRC.…”

Exploiting the critical perioperative period to improve long-term cancer outcomes

“…Similarly, studies in our animal models, showed that adding laparotomy to a minor surgical procedure, or performing a more-traumatic surgery to excise a primary tumour 36 or administer syngeneic malignant cells, 124 resulted in worse immune outcomes, but did not significantly worsen cancer outcomes. Furthermore, in these studies, the use of a nonselective β-adrenergic antagonist and a COX2 inhibitor to attenuate the responses to surgery resulted in a similar degree of improvement in cancer outcomes (including overall survival rates) in minor and major surgical procedures.…”

Identification of microRNA-487b as a negative regulator of liver metastasis by regulation of KRAS in colorectal cancer

“…Metastatic diseases occur in ~30-50% of CRC patients, either at the time of initial diagnosis or during follow-up (3,4). CRC metastasizes predominantly to the liver, and liver metastases account for at least two thirds of CRC deaths (3,5,6). Despite advances in research on primary CRC development, the mechanism for the progression from local disease to metastasis is not fully understood.…”