This retrospective cohort study revealed that ICG fluorescence angiography effectively prevents AL after laparoscopic rectal cancer surgery. Furthermore, our results suggested that ICG fluorescence imaging can reduce AL occurrence by utilizing the results of blood perfusion using ICG fluorescence.
In this study, intestinal perfusion was assessed using ICG fluorescence angiography. Traditionally, the presence of blood flow is evaluated using several clinical signs, such as palpable pulsation, peristaltic movement, or active bleeding from the marginal artery . However, these assessment methods were dependent on the surgeons. Karliczek et al. reported that the clinical judgment of surgeons appeared to have low sensitivity and specificity in predicting anastomotic leakage in colorectal anastomoses . Recently, several techniques, such as oxygen spectrometry, laser speckle imaging, thermography, and handheld vital microscopy, have been developed to evaluate intestinal perfusion [23,24,25,26]. However, these techniques are not yet widely used due to their high cost and technical complexity. ICG fluorescence angiography was first reported to be useful in colorectal surgery by Kudszus et al. . Trastulli et al. reported that using ICG fluorescence angiography led to a significant reduction in AL in colorectal surgery in a meta-analysis of 25 studies . Moreover, in a meta-analysis of 13 studies involving patients with rectal cancer, Li et al. reported that the use of ICG has a favorable effect on the reduction of the rate of AL . Considering the low cost of ICG dye in Japan (US $6), ICG fluorescence angiography is the most convenient and cost-effective method to evaluate intestinal perfusion.
Regarding AL proportions, we observed a significant reduction in the proportion of AL in the ICG group (4.1%) than in the non-ICG group (12.3%). Previous studies showed that the rates of AL when using ICG fluorescence were 0–9% [15,16,17,18, 21, 30,31,32], similar to our result. Although several studies, including meta-analyses or propensity-score-matched studies, showed the efficacy of this technique in reducing AL incidence [15,16,17,18, 28, 29, 31], no RCTs demonstrated this finding [19, 20]. It has been suggested that RCTs might have some flaws, such as sample size and endpoint selection . However, several RCTs are currently ongoing to prove the clinical benefit of routine use of ICG fluorescence [34, 35], such as Essential Trial, whose results remain unpublished. In this study, while operating time was significantly associated with AL incidence after laparoscopic rectal cancer surgery, male sex and tumor location tended to be associated with AL. These findings are consistent with those of previous reports [10, 36, 37]. Furthermore, the differences in operating surgeons and study periods, rather than those in patient characteristics or operative difficulty, might explain our finding regarding the operating time being significantly associated with AL incidence. The retrospective nature of the study should also be considered while interpreting this finding. Nonetheless, our findings suggest that ICG fluorescence has a potential benefit in terms of reducing the risk of AL in rectal cancer surgery.
In this study, the surgical plan for transection of the proximal colon was changed in 6.8% (5/73) of the patients in the ICG group. Although AL did not occur in these patients, if AL had occurred in all of them, the proportion of AL would have increased to 11%, similar to the proportion of AL in the non-ICG group (12.3%). Previous studies have shown that revisions of the proximal transection line were observed in 3.1 − 20.9% [15,16,17,18,19, 30,31,32, 38]. Of the patients with revision of the proximal transection line, AL occurred in 0–16.7%, as reported in previous studies [15,16,17,18, 31, 32, 38]. Although poor intestinal perfusion is not the only cause of AL, anastomosis with sufficient blood perfusion can contribute to reducing AL. Furthermore, considering the characteristics of patients diagnosed with AL in this study, the duration from initial surgery to AL occurrence was shorter in the non-ICG group (median, 3 days) than in the ICG group (median, 6 days), which might be a novel insight into the effect of the use of ICG fluorescence. However, as this was retrospective exploratory study, we were unable to conclusively prove this, and a prospective study is warranted. Our findings suggest that ICG fluorescence angiography to evaluate intestinal perfusion is useful for identifying areas with poor vascular perfusion, which may result in early onset of AL, and changes in the surgical plan due to ICG fluorescence visibility could contribute to a safe anastomosis.
This study has several limitations. First, blood perfusion in the distal rectum was not investigated, which might have influenced AL incidence. Second, a selection bias might have occurred because this was a retrospective cohort study that was not randomized or controlled. Third, the ICG dose used in this study was 10 mg. Although no standard dosage of ICG for evaluating intestinal perfusion has yet been established, the visibility of ICG fluorescence might be different due to the height or body weight of patients. Therefore, the results of this study do not provide definitive evidence for the effectiveness of ICG fluorescence imaging in reducing AL. Fourth, the study periods differed between the groups, and because of the relatively long-term study period, the operating surgeons also differed between the groups. This might have influenced the short-term outcomes. Further multi-institutional, randomized, controlled studies, including ongoing studies, should be planned to verify the definitive benefit of ICG fluorescence in reducing the risk of AL incidence in rectal cancer surgery. However, despite these limitations, we believe that our results are still valuable and applicable because consecutive patients who underwent laparoscopic rectal cancer surgery with anastomosis were assessed, and a standard surgical procedure was performed by a single colorectal team at a single institution.