title: Utilization of the delay phenomenon improves blood flow and reduces collagen deposition in esophagogastric anastomoses.
abstract: OBJECTIVE
  Complications of anastomotic healing are a common source of morbidity and mortality after esophagogastrostomy. The delay phenomenon is seen when a skin flap is partially devascularized in a staged procedure prior to its definitive placement, resulting in increased blood flow at the time of grafting. This effect may be applied to esophagogastrectomy, potentially reducing anastomotic complications.
  
  
  BACKGROUND
  The purpose of this investigation was to apply the delay principle to the gastrointestinal tract, investigate mechanisms by which it occurs and examine the effects of delay on anastomotic healing.
  
  
  METHODS
  Thirty-seven opossums were assigned to Sham (n = 5), Immediate (n = 14), and Delay (n = 18) groups. Each underwent laparotomy and measurement of baseline gastric fundus blood flow. The Delay and Immediate animals underwent ligation of the left, right, and short gastric vessels and subsequent measurement of gastric fundus blood flow. The Delay group underwent repeat measurement of blood flow, esophagogastrectomy, gastric tubularization, and esophagogastrostomy 28 days after vessel ligation. The Immediate group completed the procedure immediately after vessel ligation. The anastomoses in both groups were harvested 32 days after esophagogastrostomy. The Sham group underwent blood flow measurement on initial laparotomy, followed by harvesting of esophagogastric junction 60 days later. Sections taken through the anastomoses were examined with trichrome-staining and immunohistochemistry (IHC) for actin. Collagen content of the gastric submucosa 5 mm below the anastomosis was quantified, and preservation of the muscularis propria and muscularis mucosa was determined histologically. Capillary content of the esophagogastric junction was quantified using IHC for vascular endothelium in the Delay and Sham groups.
  
  
  RESULTS
  Blood flow decreased by 73% following vessel ligation in Delay and Immediate groups. The Delay group had over 3 times the gastric blood flow of the Immediate group at the time of anastomosis at 16 (interquartile range [IQR] 11-17) versus 5, (IQR 5-6) mL/min/100 g (P = 0.000003). Two Immediate animals developed anastomotic leak and died; the Delay group had no complications. Submucosal collagen content in Sham, Delay, and Immediate groups were 57% (IQR 52-62), 65% (IQR 57-72), and 71% (IQR 60-82), respectively (P = 0.0004). The median distance of full-thickness atrophy of the muscularis propria was 0.10 mm (IQR 0-0.60 mm) in the Delay group and 0.53 mm (IQR 0.03-0.80 mm) in the Immediate group (P = 0.346). Five percent of the Delay group had atrophy of the muscularis mucosa, whereas 19% of Immediate animals had atrophy of this layer (P = 0.023). Compared with the Sham group, all Delay animals developed dilation of the right gastroepiploic artery and vein. A median of 27 (IQR 23-33) capillaries per 20x field was observed in the Sham fundus and 38 (IQR 31-46) in the Delay fundus (P = 0.037).
  
  
  CONCLUSIONS
  The delay effect is associated with both vasodilation and angiogenesis and results in increased blood flow to the gastric fundus prior to esophagogastric anastomosis. Animals undergoing delayed operations have less anastomotic collagen deposition and ischemic injury than those undergoing immediate resection. Clinical application of the delay effect in patients undergoing esophagogastrectomy may lead to a decreased incidence of leak and stricture formation.
authors.affiliation: Department of Surgery, Oregon Health & Science University, Portland VA Medical Center, Portland, Oregon 97207, USA.
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Reavis
authors.forename: Eugene Y
authors.initials: EY
authors.lastname: Chang
authors.forename: John G
authors.initials: JG
authors.lastname: Hunter
authors.forename: Blair A
authors.initials: BA
authors.lastname: Jobe
mesh_terms: D000714:Anastomosis, Surgical; D000818:Animals; D001284:Atrophy; D003094:Collagen / Q000378:metabolism*; D048293:Didelphis; D004946:Esophagostomy; D005743:Gastrectomy; D005748:Gastric Fundus / Q000098:blood supply* / Q000502:physiology; D024405:Gastroepiploic Artery / Q000601:surgery; D005774:Gastrostomy; D017078:Laser-Doppler Flowmetry; D008026:Ligation; D023421:Models, Animal; D012039:Regional Blood Flow; D013997:Time Factors; D014664:Vasodilation; D014945:Wound Healing / Q000502:physiology*
chemical_list: D003094:Collagen