A novel corrective pullthrough surgery in a mouse model of Hirschsprung's disease.
OBJECTIVE
The study aimed to develop a mouse model of post-pullthrough Hirschsprung's disease that will allow investigation of mechanisms that cause postoperative complications.


METHODS
We developed a novel microsurgical pullthrough operation on Balb/C mice and evaluated its effect on growth rate and stooling pattern. Histologic assessment of the pullthrough colon was performed. The pullthrough operation was then performed on Ednrb-/- mice that have aganglionic megacolon and Ednrb+/+ littermate controls, and the outcomes compared.


RESULTS
The Balb/C pullthrough group had 97% survival at 1 week and 70% survival at 2 weeks. Body weight of the pullthrough animals declined 15% in the first week after surgery and subsequently normalized. The stooling pattern showed consistently softer stools in the pullthrough group, but no difference in frequency compared to controls. Histopathologic analyses 4 weeks postoperatively showed well-healed coloanal anastomoses. Two-week survival after pullthrough surgery in Ednrb-/- and Ednrb+/+ mice was 50.0%, and 69.2%, respectively (P = NS). Increased mortality in the Ednrb-/- mice was related to the technical challenge of performing microsurgery on smaller-sized mice with poor baseline health status.


CONCLUSIONS
Our microsurgical pullthrough operation in mice is feasible and allows systematic investigations into potential mechanisms mediating post-pullthrough complications and poor long-term results in mouse models of Hirschsprung's disease.
Division of Pediatric Surgery and The Pediatric Surgery Laboratory, Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
Lifu
L
Zhao
Zhi
Z
Cheng
Deepti
D
Dhall
Terence M
TM
Doherty
Philip K
PK
Frykman
D001003:Anal Canal / Q000601:surgery; D000714:Anastomosis, Surgical / Q000379:methods; D000818:Animals; D001835:Body Weight; D013505:Digestive System Surgical Procedures / Q000379:methods* / Q000401:mortality; D004195:Disease Models, Animal; D006627:Hirschsprung Disease / Q000401:mortality / Q000601:surgery*; D051379:Mice; D008807:Mice, Inbred BALB C; D019060:Minimally Invasive Surgical Procedures / Q000379:methods* / Q000401:mortality; D011182:Postoperative Care / Q000379:methods; D011183:Postoperative Complications / Q000503:physiopathology; D011336:Probability; D011897:Random Allocation; D012007:Rectum / Q000294:innervation / Q000601:surgery*; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D015996:Survival Rate; D016896:Treatment Outcome