Colorectal cancer is the fourth most diagnosed malignancy worldwide and surgery is one of the cornerstones of the treatment strategy. Near-infrared (NIR) fluorescence imaging is a new and upcoming technique, which uses an NIR fluorescent agent combined with a specialised camera that can detect light in the NIR range. It aims for more precise surgery with improved oncological outcomes and a reduction in complications by improving discrimination between different structures.A systematic search was conducted in the Embase, Medline and Cochrane databases with search terms corresponding to 'fluorescence-guided surgery', 'colorectal surgery', and 'colorectal cancer' to identify all relevant trials.The following clinical applications of fluorescence guided surgery for colorectal cancer were identified and discussed: (1) tumour imaging, (2) sentinel lymph node imaging, (3) imaging of distant metastases, (4) imaging of vital structures, (5) imaging of perfusion. Both experimental and FDA/EMA approved fluorescent agents are debated. Furthermore, promising future modalities are discussed.Fluorescence-guided surgery for colorectal cancer is a rapidly evolving field. The first studies show additional value of this technique regarding change in surgical management. Future trials should focus on patient related outcomes such as complication rates, disease free survival, and overall survival. 

Fluorescence-guided surgery in colorectal cancer; A review on clinical results and future perspectives

Background Colorectal cancer is the fourth most diagnosed malignancy worldwide and surgery is one of the cornerstones of the treatment strategy. Near-infrared (NIR) fluorescence imaging is a new and upcoming technique, which uses an NIR fluorescent agent combined with a specialised camera that can detect light in the NIR range. It aims for more precise surgery with improved oncological outcomes and a reduction in complications by improving discrimination between different structures. Methods A systematic search was conducted in the Embase, Medline and Cochrane databases with search terms corresponding to ‘fluorescence-guided surgery’, ‘colorectal surgery’, and ‘colorectal cancer’ to identify all relevant trials. Results The following clinical applications of fluorescence guided surgery for colorectal cancer were identified and discussed: (1) tumour imaging, (2) sentinel lymph node imaging, (3) imaging of distant metastases, (4) imaging of vital structures, (5) imaging of perfusion. Both experimental and FDA/EMA approved fluorescent agents are debated. Furthermore, promising future modalities are discussed. Conclusion Fluorescence-guided surgery for colorectal cancer is a rapidly evolving field. The first studies show additional value of this technique regarding change in surgical management. Future trials should focus on patient related outcomes such as complication rates, disease free survival, and overall survival.

Fluorescence-guided surgery in colorectal cancer; A review on clinical results and future perspectives.

Simple Summary Indocyanine green (ICG) is a simple, inexpensive compound used in abdominal surgery, particularly advantageous in colorectal and rectal surgery, allowing intraoperative real-time assessment of the blood supply to the stumps of the large intestine after resection, and to the intestine after anastomosis in order to reduce the risk of anastomotic leak. We performed a systematic review and meta-analysis to evaluate the efficacy and safety of ICG in colorectal cancer surgery in a group of 11,047 patients. The anastomotic leak rate in the ICG and non-ICG groups varied and amounted to 3.7% vs. 7.6% (p < 0.001) in all trials, 8.1% vs. 12.1% (p = 0.04) in randomized controlled trials (RCTs), and 3.1% vs. 7.3% (p < 0.001) in non-RCTs, respectively. Our meta-analysis shows that ICG perfusion assessment, with its safety, simplicity, and short time of adjustment, is a tool worth considering in decreasing the rate of complications after colorectal surgery. Abstract Despite the technological advances and improved surgical skills, the incidence of anastomotic leakage following colorectal cancer surgery still ranges from 4% to 19%. Therefore, we performed a systematic review and meta-analysis to evaluate the efficacy and safety of indocyanine green (ICG) use in colorectal cancer surgery. An online search of the Embase, MEDLINE, and Cochrane Central Register of Controlled Trials (CENTRAL) databases (from inception to 10 November 2021) was performed, in addition to manual screening. Thirty-two studies involving 11,047 patients were considered eligible for the meta-analysis. The anastomotic leak rate in the ICG and non-ICG groups varied and amounted to 3.7% vs. 7.6%, respectively (RR = 0.46; 95% CI: 0.39–0.56; p < 0.001). The rate in randomized controlled trials (RCTs) was 8.1% in the ICG group compared with 12.1% in the non-ICG group (RR = 0.67; 95% CI: 0.46–0.98; p = 0.04). In non-RCTs, it equaled 3.1% vs. 7.3%, respectively (RR = 0.43; 95% CI: 0.35–0.52; p < 0.001). Although the publications encompassed in our meta-analysis present different patients, with different factors influencing the results, a pooled analysis revealed a lower incidence of anastomotic leak in cases with ICG use. There are several other convincing advantages: safety, simplicity, and short time of the method adjustment. The presented meta-analysis indicates ICG perfusion assessment as a tool worth considering to decrease the rate of complications following colorectal surgery—valuable in the context of other, well-known risk factors.

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Safety and Efficacy of Indocyanine Green in Colorectal Cancer Surgery: A Systematic Review and Meta-Analysis of 11,047 Patients

Background Meta-analyses have demonstrated that indocyanine green (ICG) can effectively prevent anastomotic leakage (AL) after colorectal surgery. However, recent evidence from large randomized controlled trial (RCT) has suggested that ICG fluorescence angiography does not reduce the incidence of AL in colorectal surgery. This study was conducted to evaluate the value of ICG for the prevention of AL following colorectal surgery. Methods Up to September 16, 2021, PubMed, Embase, China National Knowledge Infrastructure, Web of Science, Scopus, Cochrane Library, and VIP databases were searched for RCTs and propensity-score matched (PSM) studies evaluating the use of ICG for prevention of AL after colorectal surgery. Mean differences (MDs) or odds ratios (ORs) and 95% confidence intervals (CI) were calculated. Results Twenty studies (5 RCTs and 15 PSM studies) with a total of 5,125 patients were included. ICG did not reduce the reoperation rate (OR, 0.71; 95% CI, 0.38, 1.30), conversion rates (OR, 1.34; 95% CI, 0.65, 2.78), or mortality (OR, 0.50; 95% CI, 0.13, 1.85), but ICG did reduce the incidence of AL (OR, 0.46; 95% CI, 0.36, 0.59) and symptomatic AL (OR, 0.48; 95% CI, 0.33, 0.71), and reduced the length of hospital stay (MD,−1.21; 95% CI,−2.06,−0.35) and intraoperative blood loss (MD,−9.13; 95% CI,−17.52,−0.74). In addition, ICG use did not increase the incidence of total postoperative complications (OR, 0.93; 95% CI, 0.64, 1.35), postoperative ileus (OR, 1.26; 95% CI, 0.53, 2.97), wound infection (OR, 0.76; 95% CI, 0.44, 1.32), urinary tract infection (OR, 0.87; 95% CI, 0.30, 2.59), pulmonary infection (OR, 0.23; 95% CI, 0.04, 1.45), urinary retention (OR, 1.08; 95% CI, 0.23, 5.04), anastomotic bleeding (OR, 1.53; 95% CI, 0.27, 8.60), anastomotic stricture (OR, 0.74; 95% CI, 0.24, 2.29), or operative time (MD,−9.64; 95% CI,−20.28, 1.01). Conclusions ICG can effectively reduce the incidence of AL, without prolonging the operation time or increasing postoperative complications in colorectal surgery. Systematic Review Registration www.crd.york.ac.uk/prospero/#recordDetails, identifier: CRD42021279064.

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Effect of Indocyanine Green Fluorescence Angiography on Anastomotic Leakage in Patients Undergoing Colorectal Surgery: A Meta-Analysis of Randomized Controlled Trials and Propensity-Score-Matched Studies

PILLAR of Surgical Decision-Making? Perhaps Not Without More Evidence.

Background Indocyanine green fluoroscopy has been shown to improve anastomotic leak rates in early phase trials. Objective We hypothesized that the use of fluoroscopy to ensure anastomotic perfusion may decrease anastomotic leak following low anterior resection. Design We performed a 1:1 randomized, controlled, parallel study. Recruitment of 450-1000 patients was planned over 2-years. Setting Multicenter. Patients Patients undergoing resection defined as anastomosis within 10cm of anal verge. Intervention Patients underwent standard evaluation of tissue perfusion versus standard in conjunction with perfusion evaluation using indocyanine green fluoroscopy. Main outcome measure Primary outcome was anastomotic leak, with secondary outcomes of perfusion assessment and the rate of postoperative abscess requiring intervention. Results This study was concluded early due to decreasing accrual rates. A total of 25 centers recruited 347 patients, of which 178 were randomized to perfusion and 169 to standard. The groups had comparable tumor-specific and patient-specific demographics. Neoadjuvant chemoradiation was performed in 63.5% of perfusion and 65.7% of standard (p>0.05). Mean level of anastomosis was 5.2+3.1cm in perfusion compared to 5.2+3.3cm in standard (p>0.05). Sufficient visualization of perfusion was reported in 95.4% of patients in the perfusion group. Postoperative abscess requiring surgical management was reported in 5.7% of PFN and 4.2% of standard (p=0.75). Anastomotic leak was reported in 9.0% of perfusion compared to 9.6% of standard (p=0.37). On multivariate regression analysis, there was no difference in anastomotic leak rates between perfusion and standard (OR 0.845; 95% CI (0.375, 1.905); p=0.34). Limitations The pre-determined sample size to adequately reduce the risk of type II error was not achieved. Conclusion Successful visualization of perfusion can be achieved with ICG-F. However, no difference in anastomotic leak rates was observed between patients who underwent perfusion assessment versus standard surgical technique. In experienced hands, the addition of routine ICG-F to standard practice adds no evident clinical benefit. See Video Abstract at http://links.lww.com/DCR/B560 .

Perfusion Assessment in Left-Sided/Low Anterior Resection (PILLAR III): A Randomized, Controlled, Parallel, Multicenter Study Assessing Perfusion Outcomes With PINPOINT Near-Infrared Fluorescence Imaging in Low Anterior Resection.

Background Studies to date show contrasting conclusions when comparing intracorporeal and extracorporeal anastomoses for minimally invasive right colectomy. Large multi-center prospective studies comparing perioperative outcomes between these two techniques are needed. The purpose of this study was to compare intracorporeal and extracorporeal anastomoses outcomes for robotic assisted and laparoscopic right colectomy. Methods Multi-center, prospective, observational study of patients with malignant or benign disease scheduled for laparoscopic or robotic-assisted right colectomy. Outcomes included conversion rate, gastrointestinal recovery, and complication rates. Results There were 280 patients: 156 in the robotic assisted and laparoscopic intracorporeal anastomosis (IA) group and 124 in the robotic assisted and laparoscopic extracorporeal anastomosis (EA) group. The EA group was older (mean age 67 vs. 65 years, p = 0.05) and had fewer white (81% vs. 90%, p = 0.05) and Hispanic (2% vs. 12%, p = 0.003) patients. The EA group had more patients with comorbidities (82% vs. 72%, p = 0.04) while there was no significant difference in individual comorbidities between groups. IA was associated with fewer conversions to open and hand-assisted laparoscopic approaches (p = 0.007), shorter extraction site incision length (4.9 vs. 6.2 cm; p ≤ 0.0001), and longer operative time (156.9 vs. 118.2 min). Postoperatively, patients with IA had shorter time to first flatus, (1.5 vs. 1.8 days; p ≤ 0.0001), time to first bowel movement (1.6 vs. 2.0 days; p = 0.0005), time to resume soft/regular diet (29.0 vs. 37.5 h; p = 0.0014), and shorter length of hospital stay (median, 3 vs. 4 days; p ≤ 0.0001). Postoperative complication rates were comparable between groups. Conclusion In this prospective, multi-center study of minimally invasive right colectomy across 20 institutions, IA was associated with significant improvements in conversion rates, return of bowel function, and shorter hospital stay, as well as significantly longer operative times compared to EA. These data validate current efforts to increase training and adoption of the IA technique for minimally invasive right colectomy.

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Intracorporeal and extracorporeal anastomosis for robotic-assisted and laparoscopic right colectomy: short-term outcomes of a multi-center prospective trial.

Ron G. Landmann

Papers

Perfusion Assessment in Left-Sided/Low Anterior Resection (PILLAR III): A Randomized, Controlled, Parallel, Multicenter Study Assessing Perfusion Outcomes With PINPOINT Near-Infrared Fluorescence Imaging in Low Anterior Resection.

Intracorporeal and extracorporeal anastomosis for robotic-assisted and laparoscopic right colectomy: short-term outcomes of a multi-center prospective trial.