Pathophysiology of anastomotic stricture following rectal anastomosis: Insights into mechanisms, risk factors, and preventive strategies

Table 1 Key pathophysiological mechanisms, risk factors, and preventive strategies for anastomotic stricture following rectal anastomosis

Category	Details
Pathophysiological mechanisms
Fibrosis[4,5,7,9,11]	Excessive collagen deposition (types I and III) driven by TGF-β/Smad signaling, myofibroblast activation, and imbalance of MMPs/TIMPs. Leads to dense scar tissue and luminal narrowing
Inflammation[4,7,12,13]	Dysregulated inflammatory response with IL-1, IL-6, TNF-α, and NF-κB activation. Chronic inflammation promotes fibroblast proliferation and ECM overproduction
Anastomotic leakage[2,4,11,14,15]	Leakage triggers robust inflammation (IL-1, IL-6, TNF-α) and fibrosis via TGF-β/CTGF. Hypoxia activates HIF-1α, enhancing pro-fibrotic pathways
Radiotherapy[2,8,9,15,16]	Radiation-induced microvascular injury (endarteritis obliterans) causes hypoxia, ROS production, and TGF-β/PDGF upregulation, leading to chronic fibrosis
Ischemia[6,7,13,14,17]	Poor blood supply (e.g., due to high ligation of inferior mesenteric artery) causes hypoxia, activating HIF-1α and MAPK/NF-κB pathways, resulting in fibrotic repair
Risk factors
Surgical factors[2,18]	Low anastomosis level (rectoanal/intersphincteric), hand-sewn vs double-stapling techniques, diverting stoma, technical errors (e.g., incomplete stapler closure)
Patient-related factors[2]	Male gender, advanced age, obesity, smoking, diabetes, high BMI impair wound healing and increase stricture risk
Preventive strategies
Surgical techniques[2,17,18]	Preserve left colic artery, ensure tension-free anastomosis, use double-stapling techniques with appropriate stapler size to minimize ischemia and technical errors
Perioperative care[2]	Early detection of leakage, smoking cessation, glycemic control, weight management to optimize wound healing
Emerging therapies[5]	Anti-fibrotic agents (e.g., TGF-β inhibitors), novel biomaterials to modulate fibrotic response and enhance healing

TGF-β: Transforming growth factor-beta; MMPs: Matrix metalloproteinases; TIMPs: Tissue inhibitors of metalloproteinases; IL-1: Interleukin-1; IL-6: Interleukin-6; TNF-α: Tumor necrosis factor-alpha; NF-κB: Nuclear factor-kappa B; CTGF: Connective tissue growth factor; HIF-1α: Hypoxia-inducible factor-1α; PDGF: Platelet-derived growth factor; ROS: Reactive oxygen species; ECM: Extracellular matrix; BMI: Body mass index.