327 Summary, general discussion and future perspectives and clinical research to comprehensively elucidate its features in the field of colorectal surgery. In contrast, ICG has been studied extensively in the colorectal surgery setting. A recent consensus paper highlighted its potentials including visualization and identification of extra-hepatic biliary structures, lymphatic mapping, identifying liver tumors and metastases, sentinel node/lymph node procedures, and bowel perfusion assessment 23. Both MB and ICG carry potential risks, including allergic reactions and organ toxicity. However, some experts express their worries to MB as they believe more adverse reactions to MB class products have been reported. It is important to notice that MB can only be used in patients with adequate renal function, and should be avoided in patients using serotonergic drugs like selective serotonin reuptake inhibitor (SSRIs) and serotonin-norepinephrine reuptake inhibitor (SNRIs) to avoid a serotonin syndrome 24, 26. Mild adverse effects following MB administration include hypertension, dyspnea, hemolysis, methemoglobinemia, nausea, vomiting, and chest pain at doses ranging from 2 to 7 mg/kg. Refractory hypotension and skin discoloration may occur at doses between 20 and 80 mg/kg 27. However, these doses far exceed those required for ureter delineation and bowel perfusion assessment. Therefore, such adverse events are not anticipated for the indications described in this thesis. MB is safely utilized for visualizing thyroid and parathyroid glands, pancreatic neuroendocrine tumors, and breast cancer tumors and sentinel nodes within therapeutic doses of less than 2 mg/kg 24, and we do not expect problems for bowel perfusion assessment as only low doses of MB are required for this purpose. Of course, careful consideration of patient factors and monitoring for adverse reactions are essential when using either contrast agent for fluorescence imaging. The optimalisation of NIRF systems to reduce AL rates served as the general purpose of the work presented in chapter 5 and 6. Therefore, clinical trials in which direct patient benefit is explored are necessary to further implement NIRF in colorectal surgery and improve patients’ outcomes. Pooled analysis of cohort studies has indicated that ICG fluorescence angiography decreases AL rates after colorectal resections, but comprehensive high-quality evidence has been insufficient 28. Early studies focusing on colonic anastomoses are infrequent and have not demonstrated a notable decrease in AL rates with the use of ICG fluorescence angiography 28, 29. Results on rectal resection are better described with more promising outcomes 30, 31. Due to conflicting results in the past on AL outcomes, researchers stated that more multi-center RCTs with large sample size were required to further verify the value of NIRF 32. A RCT involving 240 patients undergoing left-sided colon or rectal resection, revealed no significant difference in the AL rate between the ICG fluorescence angiography group and the control group 33. The FLAG trial included 377 patients undergoing sigmoid or rectal resection and noted a lower AL rate in the ICG group 34. Yet, this difference only occurred in grade A leaks, which include no effect on patient management. A third RCT (PILLAR III trial) including 347 patients did not report a significant reduction in AL in the ICG fluorescence angiography group compared to the control group either 35. One of the main reasons to explain previous differences and negative results is the low incidence of AL and subsequent underpowered trials 28. Besides, there is significant variability in clinical use and 14
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