Establishment of a syngeneic model of hepatic colorectal oligometastases.
BACKGROUND
Regional and systemic therapies aimed at improving the outcome for patients with colorectal hepatic metastases have met with modest yet tangible success. Currently, liver resection remains the only curative treatment, but only a minority of patients are candidates for surgery. Animal models are an ideal way to study new treatments for patients with metastatic colorectal cancer. We propose a syngeneic animal model of hepatic colorectal metastases that simulates oligometastases, which is a clinical state considered amenable to regional therapeutic strategies.


METHODS
BDIX (BD-9) rats underwent intrasplenic injection of DHD/K12/TRb (Prob/K12) cells to create hepatic metastases via the portal system. After injection of 5 x 10(6) cells, rats underwent laparotomy to determine metastatic burden. Histological analysis confirmed the presence of metastases from resected tumors.


RESULTS
Fifty-three animals were prospectively treated and observed for the development of oligometastases defined as between 1 and 10 hepatic lesions. Thirty-six (68%) of the animals developed detectable metastases while 32 (60%) developed oligometastases (average = 4.40 +/- 2.67). Four animals had overwhelming metastatic liver and peritoneal disease. All animals underwent peritoneal examination and thoracotomy to ensure localized disease. Histological analysis of five hepatectomy specimens confirmed the presence of metastatic cancer. Animals with oligometastases were healthy as evidenced by normal feeding and grooming behavior.


CONCLUSIONS
An animal model of oligometastatic colorectal cancer to the liver can reproducibly mimic the stage IV state in humans conducive to regional therapy and can be used reliably to test novel treatments and mechanisms of metastatic colorectal cancer.
Mezhir
James J
JJ
Department of Surgery, The University of Chicago, Chicago, Illinois 60637, USA.
Smith
Kerrington D
KD
Kimchi
Eric T
ET
Park
James O
JO
Lopez
Carlos A
CA
Mauceri
Helena J
HJ
Beckett
Micheal A
MA
Hellman
Samual
S
Weichselbaum
Ralph R
RR
Posner
Mitchell C
MC
D000818:Animals; D001522:Behavior, Animal; D015179:Colorectal Neoplasms / Q000473:pathology*; D004195:Disease Models, Animal; D007813:Laparotomy; D008113:Liver Neoplasms / Q000556:secondary*; D008297:Male; D009368:Neoplasm Transplantation / Q000379:methods; D051381:Rats; D011919:Rats, Inbred Strains; D013154:Spleen; D013908:Thoracotomy