The early complications of breast surgery include the skin necrosis, fat necrosis, infection, and dehiscence (6). These postoperative complications may relate to inadequate tissue perfusion after mastectomy and could be influenced by age, BMI, smoking history, and radiation therapy of patients (6, 24). A study showed a skin flap necrosis rate of 41.2% and a reoperation necrosis rate of 9% after breast surgery with a traditional clinical skin judgment(10). Therefore, it is critical to reducing postoperative complications to reduce hospital stays and the economic burden on patients. Still et al. published a study in that blood flow in a skin flap was visualized with the use of ICG in 1999 (25). Studies have shown that ICG is commonly used in skin reconstruction such as skin burns and scars (26, 27). In the process of some flap tissue transplantation, the vascularization of the distal portions of transferred is a critical factor in the success of reconstructive surgery. ICG fluorescence imaging help surgeons the evaluation of flap microcirculation and perfusion.
In the field of breast surgery, intraoperative clinical examination is the most common method of preventing skin necrosis. Recently, visualization had been gradually developed. In 2009, Komorowska-Timek et al. used preventive ICG-guided trimming that reduced skin flap necrosis rate from 15.1% to 4.0% after skin-sparing mastectomy (28). Phillips and Lanier showed the use of the introduction of Intraoperative ICG angiography reduced skin necrosis rate from 41.2% to 23.4% (10), making ICG a safe imaging agent to prevent skin flap necrosis after breast surgery. We believe that severe skin necrosis may reach the subcutaneous fat layer and has more perfusion, and the results of ICG fluorescent displays are more conductive to the judgement of the operator. Thus, early intervention with severe necrosis can lead to better skin flap survival rate.Although multiple studies have shown ICG angiography to be safe and effective at preventing skin flap necrosis, there are still some studies that have the opposite results. In a retrospective study, Sood and Glat conducted no significant difference between the ICG group and the control group on necrosis rates (p = 0.383) (13). Furthermore, Basta et al. concluded that BR was associated with postoperative complications of breast surgery (29). Therefore, skin necrosis was analyzed, and BR also was separated into a subgroup alone to explore the statistically significant differences in the present study. The pooled results indicated that the use of ICG in mastectomy and BR has no significant difference in the flap necrosis rate, but the overall incidence of necrosis was significantly reduced by ICG. Skin flap necrosis was present as mild, moderate, and severe necrosis in our included literature. Nevertheless, many papers did not differentiate and analyze the degree of skin necrosis in meta-analysis. Our study analyzed those three groups separately, and the results found that ICG could significantly reduce the incidence of severe flap necrosis. However, the ICG group and the control group with the incidence of flap necrosis had no significant difference for the mild, moderate group and overall.
Reoperation may delay hospital stay after breast surgery. However, some studies conducted disagree that ICG may reduce the rate of reoperation. A meta-analysis in 2020 by Basta et al. concluded that the risk of reoperation may decrease with the use of the ICG (29). Gustave et al. reported that there were no statistically significant differences in the reoperation rate between the ICG group and the control group (16). Our meta-analysis was conducted in agreement with the findings mentioned by Basta. The result showed obvious differences in the use of ICG as compared to the control group.
Infection is one of the serious complications after breast surgery. A recent retrospective study by Katsuya concluded that the incidence of infection has no difference between the ICG group (5%) and no the ICG group (4.8%, P=0.967) (19). Another meta-analysis study in 2020 reported that there were no significant differences in infection rates between the ICG group and control groups in patients(30). The results of our meta-analysis showed no statistically significant difference in ICG about infection after breast surgery as compared to the control group. In addition, we also pooled the data on seroma and found the total rate was not significant different in the ICG group than in the control group. Only one included study paid attention to ICG-related adverse reactions and observed none.
Previous studies have reported that age, BMI, smoking, and history of radiotherapy were related to increased skin ischemic after breast surgery (6, 31-33). Our study showed an increase in the total rate of smoking, and radiotherapy is associated with flap necrosis, but the result of the meta-analysis remains insufficient due to a lack of further statistical analysis.
Some potential limitations of this meta-analysis should be improved. First, the included studies used different ICG doses. Second, our analysis is based on six RCSs rather than RCTs, and three of them have a relatively small sample size (n < 100). Third, the present study has not further analyzed the association between BMI, smoking, age, and flap necrosis. In further study, more RCTs should be considered included.