Jayne David, Croft Julie, Corrigan Neil, Quirke Philip, Cahill Ronan A, Ainsworth Gemma, Meads David M, Kirby Andrew, Tolan Damian, Gordon Katie, Hompes Roel, Spinelli Antonino, Foppa Caterina, Wolthuis Albert M, D'Hoore André, Vignali Andrea, Tilney Henry S, Moriarty Catherine, Vargas-Palacios Armando, Young Caroline, Kelly Rachel, Stocken Deborah
Leeds Institute of Medical Research, University of Leeds, Leeds, UK.
Clinical Trials Research Unit, Leeds Institute of Clinical Trials Research, University of Leeds, Leeds, UK.
Lancet Gastroenterol Hepatol. 2025 Jul 18. doi: 10.1016/S2468-1253(25)00101-3.
Data are mixed on whether indocyanine green (ICG) fluorescence angiography can reduce the high rate of anastomotic leaks in patients undergoing surgery for rectal cancer. Therefore, we aimed to investigate the safety and efficacy of ICG fluorescence angiography in reducing the rate of clinical anastomotic leaks in these patients.
IntAct was an unblinded randomised controlled trial conducted at 28 specialist rectal cancer centres across eight European countries. Adults (≥18 years) with rectal cancer (lower margin of cancer ≤15 cm from the anal verge) medically fit for elective, curative, laparoscopic or robotic high or low anterior resection were eligible. Patients not undergoing colorectal or anal anastomosis and those with synchronous colonic tumours or recurrent or locally advanced rectal cancer requiring extended or multi-visceral excision were excluded. Eligible participants were randomly assigned (1:1) by use of minimisation with a random element to undergo surgery with or without ICG (standard care). Resections and anastomoses were done per surgeon preference. In the ICG group, surgeons first marked proximal transection levels via standard white-light laparoscopy and then administered an intravenous bolus of 0·1 mg/kg of ICG for perfusion assessment. A second 0·1 mg/kg ICG assessment was done following anastomosis. In the standard care group, only a white-light assessment of bowel perfusion was performed. The primary endpoint was the rate of clinical anastomotic leak (grades B or C, per the International Study Group of Rectal Cancer) within 90 postoperative days. Analyses were done in the intention-to-treat population for complete cases. This trial is registered with the ISRCTN registry (ISRCTN13334746) and is now complete.
Between Oct 20, 2017, and Aug 15, 2023, 2534 patients were assessed for eligibility and 766 participants were randomly assigned (383 to the ICG group and 383 to the standard care group). 501 (65%) of 766 participants were male, 726 (95%) were of White ethnicity, and the median age was 64·0 years (IQR 56·0-72·0). 343 patients in the ICG group and 355 in the standard care group were included in the intention-to-treat analysis. The rates of anastomotic leak were 11 (3%) of 343 in the ICG group and 20 (6%) in the standard care group for grade A, 11 (3%) and 31 (9%) for grade B, and 25 (7%) and 23 (6%) for grade C. Within 90 days, a clinical anastomotic leak occurred in 90 (13%) of 698 participants: 36 (10%) of 343 in the ICG group and 54 (15%) of 355 in the standard care group (adjusted odds ratio 0·667 [95% CI 0·419-1·060]; p=0·087). There were no serious adverse events related to ICG.
Although IntAct did not show a significant benefit for ICG fluorescence angiography, a signal towards a reduction in clinical anastomotic leak rate was observed. The benefit of ICG could be in preventing grade A or B leaks, given similar rates of grade C leaks between groups. Future research is needed to standardise ICG fluorescence assessment and understand its relevance to anastomotic leak.
National Institute for Health and Care Research Efficacy and Mechanism Evaluation Programme.
关于吲哚菁绿（ICG）荧光血管造影术能否降低直肠癌手术患者吻合口漏的高发生率，数据存在分歧。因此，我们旨在研究ICG荧光血管造影术在降低这些患者临床吻合口漏发生率方面的安全性和有效性。
IntAct是一项在8个欧洲国家的28个专科直肠癌中心进行的非盲随机对照试验。年龄≥18岁、患有直肠癌（癌下缘距肛缘≤15 cm）且身体状况适合择期、根治性、腹腔镜或机器人高位或低位前切除术的成年人符合条件。未进行结直肠或肛门吻合术的患者以及患有同步结肠肿瘤或需要扩大或多脏器切除的复发性或局部晚期直肠癌患者被排除。符合条件的参与者通过使用带有随机因素的最小化方法以1:1的比例随机分配，接受有或无ICG的手术（标准治疗）。切除和吻合术根据外科医生的偏好进行。在ICG组中，外科医生首先通过标准白光腹腔镜标记近端横断水平，然后静脉推注0.1 mg/kg的ICG进行灌注评估。吻合术后进行第二次0.1 mg/kg的ICG评估。在标准治疗组中，仅进行肠灌注的白光评估。主要终点是术后90天内临床吻合口漏的发生率（根据国际直肠癌研究组的标准为B级或C级）。对完整病例的意向性治疗人群进行分析。该试验已在ISRCTN注册中心注册（ISRCTN13334746），现已完成。
在2017年10月20日至2023年8月15日期间，对2534例患者进行了资格评估，766名参与者被随机分配（383例至ICG组，383例至标准治疗组）。766名参与者中，501名（65%）为男性，726名（95%）为白人，中位年龄为64.0岁（IQR 56.0 - 72.0）。ICG组的343例患者和标准治疗组的355例患者纳入意向性治疗分析。A级吻合口漏发生率在ICG组为343例中的11例（3%），标准治疗组为20例（6%）；B级分别为11例（3%）和31例（9%）；C级分别为25例（7%）和23例（6%）。在90天内，698名参与者中有90例（13%）发生临床吻合口漏：ICG组343例中有36例（10%），标准治疗组355例中有54例（15%）（调整后的优势比为0.667 [95% CI 0.419 - 1.060]；p = 0.087）。没有与ICG相关 的严重不良事件。
尽管IntAct未显示ICG荧光血管造影术有显著益处，但观察到临床吻合口漏发生率有降低的趋势。鉴于两组C级漏发生率相似，ICG的益处可能在于预防A级或B级漏。未来需要开展研究以规范ICG荧光评估并了解其与吻合口漏的相关性。
英国国家卫生与保健研究所疗效与机制评估项目。
