Dissertation committee:
Γ. Βάος, Ομότιμος Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Δ. Περρέα, Ομότιμη Καθηγήτρια, Ιατρική Σχολή, ΕΚΠΑ
Κ. Χ. Κόντζογλου, Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Ν. Νικητέας, Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Δ. Δημητρούλης, Αν. Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Σ. Κύκαλος, Επ. Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Γ. Τσουρουφλης, Επ. Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Summary:
Background/Aim: Diabetes mellitus is an established risk factor of colorectal anastomosis failure. The purpose of the present study was to evaluate the effect of TISSEEL® in anastomotic healing. Materials and Methods: Forty male, Sprague-Dawley rats were used. Diabetes was induced in half of them by intraperitoneal injection of Streptozotocin, 60 mg/kg. One week after the injection, animals were operated and a 1 cm segment was removed and an end-to-end hand sewn anastomosis was performed. TISSEEL® was applied in each group (diabetic, non - diabetic) following randomization. Results: The pathology analysis revealed improved tissue remodeling in the TISSEEL® group, both for the normoglycemic and the diabetic group. Specifically, the extent of inflammation was decreased (p<0.001), whereas fibroblast and collagen formation were improved (p=0.040 and p=0.008). Neovascularization was also improved (p=0.047). Conclusion: Application of TISSEEL® on colorectal anastomoses improves healing in rats that suffer from severe hyperglycemia.Surgical operation is currently the definitive treatment option both for colorectal cancer and a variety of benign colorectal modalities, such as inflammatory bowel disease (IBD), inflammatory strictures, diverticulosis - diverticulitis, obstructive defecation, volvulus, fistulae etc. Despite the fact that colorectal surgeons undergo a high-level training and specialization in advanced techniques, colorectal operations still demonstrate serious complications The most frightening and dramatic complication of colorectal resections with restorative anastomoses is anastomotic dehiscence. Anastomotic leakage remains a relatively frequent complication of colorectal operations even in high volume specialized centers, with reported rates of 2.5%-15% for rectal cancer resections and 3%-7% after colon cancer surgery (4). The consequences of this complication are devastating as it has been related to higher recurrence rates, increased morbidity and mortality rates, elevated treatment costs and negative influence in the quality of life of patients.Despite technological advances, including transanal total mesorectal excision (TME), laparoscopic and robotic approach, and the new trends followed during post-operative management of patients that undergo colorectal resection, such as enhanced recovery after surgery (ERAS), there are several risk factors that still exert a significant impact on the outcome of colorectal anastomoses. So far, patient-related factors (male sex, ASA score>II, radiotherapy, immunosuppressive therapy, bevacizumab intake), tumor-related factors (distal size>3 cm, advanced stage, emergency surgery, metastatic disease), comorbidities (diabetes, cardiovascular disease, poor nutrition) and operation-related factors (operative time, blood loss, need for transfusion) have been considered as determinants of failed anastomotic healing and leakage. Diabetes mellitus has a special position among the previously mentioned risk factors, as it is a well-established independent factor for anastomotic leakage, that has been associated to increased mortality after anastomotic dehiscence as well. Previous studies have suggested that the negative impact of diabetes mellitus on tissue healing is based on the exacerbated inflammatory processes. Diabetes also dysregulates the transformation of macrophages from their inflammatory-state into their healing-state. Furthermore, the disease results in the formation of extracellular neutrophilic traps that contain chromatin and cytotoxic proteins, a process called NETosis, that damages healthy tissues. Peripheral angiopathy is another factor that is frequently encountered in diabetic patients which per se results in impairment of the integrity of colorectal anastomoses. Diabetes affects a large number of physiological factors involved in the healing process, such as growth factor production, angiogenic response, collagen concentration, tissue granulation and extracellular matrix accumulation and remodeling by matrix metalloproteinases. However, fibrin sealants have been used as hemostatic factors and enhancers of the wound healing process in various surgical procedures including gastrointestinal anastomoses, plastic surgery, gynecologic and urologic procedures The aim of the present study was to investigate the effect of TISSEEL®, which is a fibrin sealant that simulates the final stages of the coagulation cascade, in tissue healing of colorectal anastomoses in diabetic rats.
Keywords:
Anastomosis, Colon, Leakage, Healing, Diabetes, Adhesive, Haemostatic, Animal model
