Gastric Ischemic Conditioning Increases Neovascularization and Reduces Inflammation and Fibrosis During Gastroesophageal Anastomotic Healing

Kyle A Perry, MD, James Liu, MD, Ambar Banarjee, MD, Mark R Wendling, Nilay Shah, MD, W S Melvin, MD. Center for Minimally Invasive Surgery, The Ohio State University, Columbus, OH


INTRODUCTION: Gastric pull-up reconstruction is the most common approach to esophageal replacement during esophagectomy. The incidence of anastomotic leak and stricture remain high, and gastric devascularization followed by delayed esophageal resection has been proposed to minimize these complications. We aimed to investigate the effect of ischemic conditioning duration on anastomotic wound healing in an animal model of esophagogastrectomy.
METHODS: North American Opossums (Didelphis virginiana) were randomized to 4 study groups. Group A underwent immediate resection and gastroesophageal anastomosis while Groups B, C, and D were treated with delayed resection and anastomosis following a gastric ischemic conditioning period of 7, 30, and 90 days respectively. Gastric conditioning was performed by ligating the left, right, and short gastric vessels leaving the right gastroepiploic artery as the sole blood supply to the stomach. Following the conditioning period, an intraabdominal esophagogastric resection and anastomosis was performed. All animals were euthanized for tissue procurement 10 days after anastomosis. Outcome variables included anastomotic bursting pressure, micro-vessel concentration, tissue inflammation, and collagen deposition. Quantitative micro-vessel count was performed by counting the number of blood vessels per high power field; and inflammation and degree of fibrosis were semiquantitatively assessed by assigning grades of 0 to 2 based on severity. These assessments were performed by a trained pathologist blinded to the treatment groups.
RESULTS: 24 opossums were randomized to groups A (n=7), B (n=8), C (n=5) and D (n=4) and completed the protocol. Subclinical anastomotic leak was discovered at necropsy in 6 animals including 4 in group A, and 1 animal in groups B and C (p=0.295). The outcome data are summarized in the Table below. The anastomotic bursting pressure did not differ significantly between groups. Compared to animals undergoing immediate reconstruction, a 7 day ischemic conditioning time did not produce increased neovascularity. Animals with 30 day conditioning time, however, showed significantly increased microvessel counts compared to unconditioned animals. The degree of inflammation at the healing anastomosis decreased significantly as the ischemic conditioning period increased. Collagen density, a measure of anastomotic site fibrosis, varied from 0.5±0.5 in Group-A to a high of 1.8±0.4 in Group-B before declining to 1.2±0.8 and 0.6±0.5 in Groups C and D (p=0.022).
CONCLUSION: Compared to animals undergoing immediate resection and anastomosis, those treated with 30 days of gastric ischemic conditioning showed significantly increased neovascularity and decreased inflammation at the healing anastomosis. These changes were not evident following 7 days of ischemic conditioning, whereas extending the ischemic conditioning period to 90 days resulted in decreased inflammation, fibrosis, and neovascularity. These data suggest that an ischemic conditioning period longer than 7 days is required to achieve the desired effect on wound healing. Larger studies will be required to assess the impact of a prolonged ischemic conditioning period on anastomotic strength.

Ischemic Conditioning Time (days)073090 
Bursting Pressure (mmHg)64.7±34.452.4±38.365±24.167.3±21.90.350
Microvessel Count (No./hpf)19.5±1.618.8±0.8  0.491
 19.5±1.6 22.6±1.6 0.003
 19.5±1.6  14.3±1.80.001


Session Number: SS01 – Basic Science
Program Number: S002

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