Liver Regeneration Model in Cynomolgus Monkeys

Completed
4403Neuraxial Drug Delivery: Past, Present and Future

Date: Thursday, September 15, 2022
Time: 10:30 am PT
Duration: 30 Minutes
Track: Thursday - Track 1
Room: Salon ABCD
Speaker: Randy Pielemeier
Moderator: Melanie Graham

Introduction: About 41,260 new cases (28,600 in men and 12,660 in women) over liver cancer will be diagnosed in 2022 according to the American Cancer Society website. A model resecting approximately 60% of the liver by weight in cynomolgus monkeys is valuable in evaluating potential therapies that encourage natural regrowth of the liver post resection in human patients.
Methods: Spanning three separate studies, a laparotomy was performed on a total of 26 animals, resecting approximately 60% of the total liver volume (by weight) of each animal’s liver. Liver volume was calculated based on historical organ (liver) weights measured at necropsy, determined to be approximately 2% of the animal’s total body weight. The right and left median lobes were resected across the liver using a bipolar generator with a Covidien Ligasure ™ hand piece. Using conventional dissection and duct ligation techniques, the left lateral lobe was resected with silk ligatures. The right lateral lobe was left intact.
Liver biopsies were collected from each animal either under ultrasound guidance or laparoscopically.
Results: Post Liver resection, one animal was euthanized with potential hepatic encephalopathy. Several days post operative, transient inappetence was observed.
Due to complications in dissection while attempting to laparoscopically collect the biopsy from the cut/regenerating edge of the liver, two animals were required to be euthanized. Significant adhesions were seen on the left and right median liver lobes cut edge, and/or between the stomach, mesentery, and diaphragm. In later animals, resection of the right medial lobe was modified to reduce biopsy complications.
Conclusion: Post operative recovery was manageable with additional enrichment foods to encourage appetite along and pain management based on pain scoring. Inappetence and pain was likely caused by painful and reduced peristalsis in the stomach due to formation and breakdown of adhesions. Ultrasound guided needle biopsy had minimal complications except for 1 kidney injury.
Modifications to the resection of the right medial lobe, by curving the resection away from the diaphragm on the right edge of the right medial lobe, mitigated laparoscopic biopsy complications in later cases. This alteration led to better access and less adhesions to the liver.

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Speaker


Charles River Laboratories

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