- Email: [email protected]
The Risk Factor of Anastomotic Hypoperfusion in Colorectal Surgery
j o u r n a l o f s u r g i c a l r e s e a r c h d e c e m b e r 2 0 1 9 ( 2 4 4 ) 2 6 5 e2 7 1
Available online at www.sciencedirect.com
ScienceDirect journal homepage: www.JournalofSurgicalResearch.com
The Risk Factor of Anastomotic Hypoperfusion in Colorectal Surgery Takayuki Ogino, MD, PhD,a,b,* Tomoki Hata, MD,a Junji Kawada, MD, PhD,a Miho Okano, MD, PhD,a Yongkook Kim, MD, PhD,a Masaki Okuyama, MD, PhD,a and Toshimasa Tsujinaka, MD, PhDa a b
Department of Surgery, Kaizuka City Hospital, Osaka, Japan Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan
article info
abstract
Article history:
Background: Inadequate blood flow is an important risk factor for anastomotic leakage.
Received 29 March 2019
Indocyanine green (ICG) fluorescence imaging allows intraoperative assessment of intes-
Received in revised form
tinal blood flow. This study determined the risk factor of anastomotic hypoperfusion in
4 May 2019
colorectal surgery using ICG fluorescence imaging.
Accepted 14 June 2019
Methods: This study included 74 consecutive patients who underwent colorectal surgery
Available online xxx
between April 2017 and March 2018. ICG was injected intravenously after dividing the mesentery and central vessels along the planned transection line, but before completing
Keywords:
the anastomosis. Intraoperative blood flow was evaluated using ICG fluorescence imaging.
Hypoperfusion
With regard to the patient-, tumor-, and surgery-related factors, anastomotic perfusion
Colorectal surgery
was evaluated based on the changed transection line and prolonged (more than 60 s)
ICG fluorescence imaging
perfusion time.
Anticoagulation therapy
Results: Intraoperative ICG fluorescence imaging was performed in all patients, and no
Anastomotic leakage
adverse events were associated with ICG injection. Based on the perfusion assessment, we changed the transection line in six patients (8.1%). The prolonged perfusion time was observed in nine patients (12.2%). The postoperative course was uneventful in 63 (85.1%) patients, but one patient (1.4%) had postoperative anastomotic leakage. The changed transection line was significantly associated with anticoagulation therapy (P ¼ 0.029). Wellknown risk factors, including surgical site, sex, smoking, blood loss, operative time, and preoperative chemoradiotherapy, were not related to the changed transection line. Prolonged ICG perfusion time was not associated with any patient-, tumor-, or surgery-related factors. Conclusions: The evaluation of intraoperative blood flow using ICG fluorescence imaging may be able to detect anastomotic hypoperfusion, and anticoagulation therapy is a risk factor of anastomotic hypoperfusion in colorectal surgery. ª 2019 Elsevier Inc. All rights reserved.
* Corresponding author. Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, 2-2 E2 Yamadaoka, Suita, Osaka 565-0871, Japan. Tel.: þ81 6 6879-3251; fax: þ81 6 6879-3259. E-mail address: [email protected] (T. Ogino). 0022-4804/$ e see front matter ª 2019 Elsevier Inc. All rights reserved. https://doi.org/10.1016/j.jss.2019.06.050
266
j o u r n a l o f s u r g i c a l r e s e a r c h d e c e m b e r 2 0 1 9 ( 2 4 4 ) 2 6 5 e2 7 1
Introduction Anastomotic leakage (AL) remains a serious complication that is associated with increased perioperative mortality and length of hospital stay, as well as local cancer recurrence. Advances in surgical imaging have resulted in better clinical results in colorectal surgery.1-5 The reported incidence of AL after colorectal surgery ranges from 3% to 20%. The site of the anastomosis, sex, smoking, blood loss, operative time, preoperative chemotherapy, and preoperative radiation are associated with elevated AL rates.1,2,6-8 Inadequate blood flow can result in the failure of anastomotic healing.9 Although patient-related factors cannot be easily altered, assessment of bowel perfusion, bowel viability, and anastomotic integrity can potentially be improved. Clinical evaluations are performed based on gross findings, such as color, peristalsis, pulsation, and bleeding. However, these evaluations are subjective, and it can be difficult to quantify the actual blood supply and perfusion of the anastomosis. Therefore, objective and accurate measurements of intestinal blood flow are needed to prevent AL. In recent years, near-infrared (NIR) fluorescence imaging using indocyanine green (ICG) has been reported as a promising method for accurately evaluating intraoperative intestinal blood flow.10-14 ICG is a sterile, water-soluble, tricarbocyanine compound dye that absorbs NIR light at 800 nm and emits fluorescent light at 830 nm. After intravenous injection, ICG rapidly and extensively binds to plasma proteins and is confined to the intravascular compartment; it is cleared by the liver into bile in a few minutes. ICG contains no more than 5.0% sodium iodide and should be used with caution in patients with a history of allergy to iodides or iodinated imaging agents.14,15 Under NIR light, ICG emits fluorescence, allowing intraoperative assessment of intestinal blood flow. Anastomotic hypoperfusion could influence the AL rate. Several articles demonstrated the safety and feasibility of ICG fluorescence imaging in colorectal surgery;10-14 however, few studies have evaluated the risk factor of anastomotic hypoperfusion. Therefore, we performed a prospective, singlecenter, open-label clinical study to assess the risk factor of anastomotic hypoperfusion in colorectal surgery using ICG fluorescence imaging.
for four emergency cases. The anesthesiologist administered a 5 mg bolus of ICG intravenously after dividing the mesentery and central vessels along the planned transection line, but before completing the anastomosis. Intraoperative blood flow was evaluated using the NIR light camera system (Photodynamic Eye System, Hamamatsu Photonics, Japan). This camera was fixed 15 cm from the extracted specimen. The time from completing the ICG injection to the first visible fluorescence signal was recorded. The cutoff for prolonged perfusion was set to 60 s according to previous reports.1,4 Perfusion was assessed as inadequate or adequate on both the proximal and distal transection lines (Fig. 1), except in the case of low anterior resection (LAR) that only the proximal line was assessed. If fluorescence imaging showed hypoperfusion at the initially planned line of transection (Fig. 2), which was equivalent to the position on the cut end of the mesentery and marginal vessels, the transection line was changed to a more proximal or distal line that was determined to have normal perfusion by ICG fluorescence imaging. Anastomotic perfusion was evaluated based on the changed transection line and prolonged ICG perfusion time. In case without anastomosis such as Hartmann operation and abdominoperitoneal resection, perfusion of the proximal stumps was evaluated. All surgeries after intravenous administration of ICG were recorded and reviewed by board-certificated colorectal surgeons.
Data collection All data were prospectively collected and stored in a database, including age, sex, body mass index (BMI), American Society of Anesthesiologist score, preoperative diagnosis, history of preoperative chemotherapy and radiotherapy, steroid therapy, history of smoking or alcohol use, and complete medical history. The data were summarized as means or medians, ranges (minimum to maximum), and percentages for all patients. Intraoperative data included the site of the
Methods Patients ICG fluorescence imaging was used in consecutive patients who underwent colorectal surgery at Kaizuka City Hospital, Japan, from April 2017 to March 2018. Patients with a history of allergic hypersensitivity to ICG or iodine, as well as pregnant or lactating women, were not eligible for ICG imaging.
ICG fluorescence imaging and surgical procedure Three board-certified colorectal surgeons at our institution performed all procedures. Every patient underwent standard bowel preparation and received antibiotic prophylaxis except
Fig. 1 e Perfusion of the planned transection line was assessed by ICG fluorescence imaging. In case that the line located in normal perfusion area, the transection and anastomosis were performed at the line.
ogino et al risk factor of anastomotic hypoperfusion
Fig. 2 e The transection and anastomosis line was changed to normal perfusion area in case that ICG fluorescence imaging showed hypoperfusion at the initially planned transection line. Short dashed line indicates bowel tract.
anastomosis, vessel ligation, splenic flexure mobilization, the use of a drainage tube, intraoperative transfusions, operative time, intraoperative bleeding, the added procedure time using ICG fluorescence imaging, and the time for perfusion fluorescence after ICG injection. ICG fluorescence images were recorded and judged qualitatively in real time. Any change in the operative protocol prompted by the findings of ICG fluorescence imaging was documented. Postoperative complications (30-day morbidity and mortality) were also included in the analysis, with their severity classified according to the Clavien-Dindo classification system. Only symptomatic AL was included in the analysis. Asymptomatic AL was not considered because routine contrast enema or colonoscopy was not performed after surgery.
presented in Table 1. The median patient age was 71 y (range, 40 to 92), 40 patients (54.1%) were male and 34 patients (45.9%) were female, and the mean BMI was 20.6 kg/m2 (range, 14.7 to 28.2). Resection for colorectal cancer was the main indication for surgery (54 patients, 73.0%); in these cases, complete mesocolic excision with central vascular ligation was performed. The other patients had the following indications for surgery: five patients (6.8%) had diverticulitis, seven patients (9.5%) had bowel involvement from ovarian or pancreatic cancer, and the remaining eight patients (10.8%) had ileus. The surgical indication for ileus was suspected intestinal ischemia or intestinal ischemia that was not improved by conservative treatment with ileus tube or nasogastric tube for 2 wk. Preoperative chemoradiotherapy was performed in seven patients (9.5%), 10 patients (13.5%) had anticoagulation therapy, and three patients (4.1%) had steroid treatment. Finally, 17 patients (23.0%) had diabetes mellitus. The intraoperative data are listed in Table 2. Regarding the operative procedure, laparoscopic surgeries were performed in 49 patients (66.2%) and open surgeries were performed in 25 patients (33.8%). A loop ileostomy was performed simultaneously in eight patients (10.8%) who underwent LAR. The median operative time was 243 min (range, 58 to 1212), and the median blood loss was 60 mL (range, 3 to 3400).
ICG fluorescence imaging The perfusion assessment data are shown in Table 3. There were no adverse events associated with ICG injection, and
Table 1 e Patient characteristics (n [ 74). Age, y, median SD
The protocol for this research project was approved by the Ethics Committee of Kaizuka City Hospital. The procedures conformed to the provisions of the Declaration of Helsinki of 1995 as revised in Brazil in 2013. Written informed consent was obtained from all patients for the use of their clinical data.
71.0 10.4
Sex, n (%) Male
Ethics statement
267
Female BMI, kg/m2, mean SD
40 (54.1) 34 (45.9) 20.6 3.6
>25
11 (14.9)
25
63 (85.1)
ASA, n I/II/III
3/59/12
Indications for surgery, n (%)
Statistical analysis
Colorectal cancer Diverticulitis
All statistical analyses were conducted using GraphPad Prism software, version 5.0 b. The chi-square test and Fisher’s exact test were used to compare and analyze categorical variables. All analyses were two-tailed with P < 0.05 considered significant.
54 (73.0) 5 (6.8)
Bowel involvement from other cancer
7 (9.5)
Ileus
8 (10.8)
Preoperative chemoradiotherapy, n (%) Anticoagulation therapy, n (%)
7 (9.5) 10 (13.5)
Smoking, Brinkman index, n (%)
Results Patients A total of 74 consecutive patients who underwent colorectal surgery were analyzed. The patient characteristics are
>400
20 (27.0)
400
14 (18.9)
non-Smoker
40 (54.1)
Diabetes mellitus, n (%)
17 (23.0)
Steroids use, n (%)
3 (4.1)
Alcohol daily, n (%)
22 (29.7)
268
j o u r n a l o f s u r g i c a l r e s e a r c h d e c e m b e r 2 0 1 9 ( 2 4 4 ) 2 6 5 e2 7 1
Table 2 e Perioperative data (n [ 74). Operation, n
Table 4 e Postoperative data (n [ 74).
Laparoscopic
Open
18
12
Right-sided colectomy Left-sided colectomy Anterior resection Low anterior resection
14
4
2
2
10
3
Hartmann operation
1
4
Abdominoperineal resection
4
0
Ileostomy, n (%) Operative time, min, median SD
8 (10.8)
27 (36.5)
300, n (%)
47 (63.5)
34 (45.9)
50, n (%)
40 (54.1)
intraoperative ICG fluorescence imaging was performed in all patients. The mean time for perfusion fluorescence after ICG injection was 41.1 s (range 10 to 136). The mean added procedure time using ICG fluorescence imaging was 6.7 min (range, 2 to 16). Based on the ICG fluorescence imaging perfusion assessment, we changed the transection line in six patients (8.1%).
Postoperative morbidity ICG injection was not related to long-term or short-term morbidity. The postoperative course was uneventful in 63 (85.1%) patients, whereas the remaining 11 (14.9%) had the postoperative complications listed in Table 4. Ileus was observed in two patients, who recovered with a nasogastric tube (Clavien-Dindo grade II). Wound infection was observed in four patients, who mostly recovered with only wound washing (Clavien-Dindo grade I or II). Urinary retention was observed in four patients, who recovered with the use of a ureteral catheter or medication (Clavien-Dindo grade I or II). AL was detected in one patient (Clavien-Dindo grade IIIa); however, anastomotic hypoperfusion was not seen as a causative factor. In this case, LAR and ureteroneocystostomy were performed during the same surgery. On postoperative day 5, AL was detected after the leakage of ureteroneocystostomy that was observed on postoperative day 2. These two anastomosis sites were very close. It seemed that this AL was not caused by anastomotic hypoperfusion but rather by extended infection because of leakage associated with the ureteroneocystostomy. The median hospital stay
Table 3 e Perfusion assessment (n [ 74). 74 (100.0)
Time of procedure, min, mean SD
6.7 4.5
Time for perfusion fluorescence after ICG injection, s, mean SD
41.1 26.6
Change in the resection line, n (%)
Ileus Wound infection Urinary retention Length of hospital stay, d, median SD
IIIa: 1 II: 2 I: 3, II: 1 I: 3, II: 1 13.0 9.8
Reoperation, n
0
Mortality, n
0
was 13 d (range, 7 to 56 d). None of the patients required reoperation, and no mortality occurred.
60.0 859.1
>50, n (%)
ICG fluorescence imaging acquired, n (%)
Anastomotic leakage
243.0 169.8
>300, n (%) Blood loss (mL, median SD)
Postoperative morbidity, Clavien-Dindo grade: n
6 (8.1)
Risk factors of anastomotic hypoperfusion We investigated whether patient-, tumor-, or surgery-related factors were associated with a changed transection line or prolonged ICG perfusion time (Table 5). We classified the patients into two groups each in two categories: (1) a group with a changed transection line versus a group with no changed transection line and (2) a group in which the time for perfusion fluorescence after ICG injection was more than 60 s versus a group in which the time was less than 60 s. The changed transection line was significantly associated with anticoagulation therapy (P ¼ 0.029). No significant differences were detected according to changed versus unchanged resection line in terms of age, sex, BMI, American Society of Anesthesiologist, diabetes mellitus, smoking, alcohol, steroid use, preoperative chemoradiotherapy, operation site, operative time, and blood loss. Prolonged (more than 60 s) ICG perfusion time was not associated with any patient-, tumor-, or surgery-related factor.
Discussion Although multiple factors can contribute to AL, anastomotic hypoperfusion is a main factor. A previous report suggested that anastomotic hypoperfusion is related to late AL, whereas surgical technique is mainly related to early AL.16 Even a mechanically intact anastomosis can breakdown because of vascular insufficiency in some patients. Therefore, determining intestinal blood flow remains an area that may be able to improve outcomes by the introduction of ICG fluorescence imaging. Earlier reports found that ICG imaging can aid in surgical decision-making and improving outcomes in cardiothoracic, hepatobiliary, gastrointestinal, foregut, transplant, and plastic surgery.17-22 However, only a few studies have demonstrated the benefits of angiography in colorectal surgery.11-14,23 Previous studies demonstrated that fluorescence angiography in colorectal surgery resulted in a change in the planned transection line (5% to 40%) and reduction of AL (4% to 7%).10,11,24 Kudszus et al. reported that fluorescence angiography shortened hospital stays and reduced revision in elective resections and patients older than 70 y.12 Moreover, in a multi-institutional prospective study, PILLAR-II, fluorescence
269
ogino et al risk factor of anastomotic hypoperfusion
Table 5 e Patient-, tumor-, and surgery-related factors with potential associations with changed resection line and prolonged ICG perfusion time. Changed resection line (n ¼ 6)
Variable
n/total n
%
Age, y
P Value
Prolonged perfusion time (60 s, n ¼ 9) n/total n
%
1
0.716
75
2/22
9.1
2/22
9.1
<75
4/52
7.7
7/52
13.5
5/40
12.5
5/40
12.5
1/34
2.9
4/34
11.8
25
1/11
9.1
2/11
18.2
<25
5/63
7.9
7/63
11.1
8/62
12.9
1/12
8.3
8/64
12.5
1/10
10
Sex
0.209
Male Female 2
BMI (kg/m )
1
1
ASA
0.615
1
I/II
5/62
8.1
III
1/12
8.3
Anticoagulation therapy
1
0.029
No
3/64
4.7
Yes
3/10
30
No
4/57
7
Yes
2/17
11.8
DM
1
0.616
Smoking
0.197 5/57
8.8
4/17
23.5
4/40
10
5/34
14.7
6/52
10.9
3/22
13.6
0.209
No
5/40
12.5
Yes
1/34
2.9
Alcohol
0.724
1
No
4/52
7.7
Yes
2/22
9.1
Steroid use
1
0.227
1
No
5/71
7
9/71
12.7
Yes
1/3
33.3
0/3
0
8/67
11.9
1/7
14.3
3/17
17.6
6/57
10.5
Preoperative chemoradiotherapy
1
No
6/67
9
Yes
0/7
0
Operation site
1
0.616
Rectum
2/17
11.8
Colon
4/57
7
Operative time, s
0.421
0.406
0.273
>300
1/27
3.7
5/27
18.5
300
5/47
10.6
4/47
8.5
8.8
Blood loss, mL
1
0.494
>50
3/34
8.8
3/34
50
3/40
7.5
6/40
imaging changed surgical plans in 7.9% of cases in which it was used. In that study, the overall incidence of AL was 1.4%, and no AL occurred in the 11 patients who had a change of surgical plan.13 Ris et al. reported that ICG imaging changed the site of bowel division in 5.8% of patients with no leaks, and the AL rate was 2.4%.23 On the other hand, Kin et al. reported that fluorescence angiography did not reduce the number of colorectal ALs.25 Wada et al. reported that the difference in the
P Value
15
fluorescence signal between maximum and baseline was the most indicative factor of AL, with a sensitivity of 100% and specificity of 92.5%.26 Intraoperative evaluation of intestinal blood flow using ICG fluorescence imaging is considered to be useful because hypoperfusion could be detected even if macroscopically judged normal perfusion. However, few studies have assessed its utility and the risk factors of hypoperfusion.
270
j o u r n a l o f s u r g i c a l r e s e a r c h d e c e m b e r 2 0 1 9 ( 2 4 4 ) 2 6 5 e2 7 1
As is the case in most previous studies with 0.05 to 0.2 mg/ Kg ICG, 5 mg of intravenous ICG was used at a concentration of 2.5 mg per 1 mL water in our study.11-14,23-25 Imaging was performed successfully in all cases, and no complications were attributable to the use of ICG or the device. The incidence of changes in the bowel transection line was 8.1% due to relative ischemia observed by ICG fluorescence imaging. In this study, the changed transection line was significantly associated with anticoagulation therapy. All patients who were receiving regular anticoagulation therapy had cardiovascular disease, which indicates that the intestinal blood flow was affected by arteriosclerosis. However, well-known risk factors, such as operation site, sex, smoking, blood loss, operative time, and preoperative chemoradiotherapy, were not related to changed transection line. Prolonged perfusion time was not associated with any patient-, tumor-, or surgeryrelated factors in this study. This study has some limitations due to inherent biases associated with being a prospective single-armed study. The heterogeneous population and the small sample size did not allow us to draw definitive conclusions. The adequacy of the transection line as determined by ICG fluorescence was interpreted subjectively, which could be seen as a limitation. Therefore, it is important to quantitatively assess the ICG fluorescence signal. In addition, the intestinal blood flow needed for proper healing of an intestinal anastomosis remains unclear. Further studies are needed to address these issues, including a large multi-institutional randomized controlled study. The blood flow evaluation at not only the proximal but also the distal site is important for the success of the anastomosis.27 In this study, the distal transection line could not be evaluated during LAR because of an NIR light system for open surgery. This limitation could be solved by using a laparoscopic NIR light system. Minimal anastomotic tension is also thought to be a requirement for preventing AL, as is intestinal blood flow.16 However, no experimental studies have investigated the role of tension in intestinal anastomosis. It is difficult to design studies to evaluate anastomotic tension in a clinical setting. Although several risk factors for AL are beyond surgical control, our data demonstrate that evaluating intraoperative blood flow using ICG fluorescence imaging may be able to detect anastomotic hypoperfusion, and anticoagulation therapy is a risk factor of anastomotic hypoperfusion in colorectal surgery.
Acknowledgment Authors’ contribution: T.O. designed the work and wrote the manuscript. T.H., J.K., M.O., Y.K., M.O., and T.T. assisted with acquisition of the images and also with manuscript revision. All authors read and approved the final manuscript.
Disclosure This study received no funding. The authors declare no conflicts of interest.
references
1. Kingham TP, Pachter HL. Colonic anastomotic leak: risk factors, diagnosis, and treatment. J Am Coll Surg. 2009;208:269e278. 2. Chadi SA, Fingerhut A, Berho M, et al. Emerging trends in the etiology, prevention, and treatment of gastrointestinal anastomotic leakage. J Gastrointest Surg. 2016;20:2035e2051. 3. Mirnezami A, Mirnezami R, Chandrakumaran K, Sasapu K, Sagar P, Finan P. Increased local recurrence and reduced survival from colorectal cancer following anastomotic leak: systematic review and meta-analysis. Ann Surg. 2011;253:890e899. 4. Hirst NA, Tiernan JP, Millner PA, Jayne DG. Systematic review of methods to predict and detect anastomotic leakage in colorectal surgery. Colorectal Dis. 2014;16:95e109. 5. Hammond J, Lim S, Wan Y, Gao X, Patkar A. The burden of gastrointestinal anastomotic leaks: an evaluation of clinical and economic outcomes. J Gastrointest Surg. 2014;18:1176e1185. 6. Vallance A, Wexner S, Berho M, et al. A collaborative review of the current concepts and challenges of anastomotic leaks in colorectal surgery. Colorectal Dis. 2017;19:1e12. 7. Kang CY, Halabi WJ, Chaudhry OO, et al. Risk factors for anastomotic leakage after anterior resection for rectal cancer. JAMA Surg. 2013;148:65e71. 8. Qu H, Liu Y, Bi DS. Clinical risk factors for anastomotic leakage after laparoscopic anterior resection for rectal cancer: a systematic review and meta-analysis. Surg Endosc. 2015;29:3608e3617. 9. Sheridan WG, Lowndes RH, Young HL. Tissue oxygen tension as a predictor of colonic anastomotic healing. Dis Colon Rectum. 1987;30:867e871. 10. Hellan M, Spinoglio G, Pigazzi A, Lagares-Garcia JA. The influence of fluorescence imaging on the location of bowel transection during robotic left-sided colorectal surgery. Surg Endosc. 2014;28:1695e1702. 11. Jafari MD, Lee KH, Halabi WJ, et al. The use of indocyanine green fluorescence to assess anastomotic perfusion during robotic assisted laparoscopic rectal surgery. Surg Endosc. 2013;27:3003e3008. 12. Kudszus S, Roesel C, Schachtrupp A, Hoer JJ. Intraoperative laser fluorescence angiography in colorectal surgery: a noninvasive analysis to reduce the rate of anastomotic leakage. Langenbecks Arch Surg. 2010;395:1025e1030. 13. Jafari MD, Wexner SD, Martz JE, et al. Perfusion assessment in laparoscopic left-sided/anterior resection (PILLAR II): a multiinstitutional study. J Am Coll Surg. 2015;220:82e92. 14. Ris F, Hompes R, Cunningham C, et al. Near-infrared (NIR) perfusion angiography in minimally invasive colorectal surgery. Surg Endosc. 2014;28:2221e2226. 15. Alander JT, Kaartinen I, Laakso A, et al. A review of indocyanine green fluorescent imaging in surgery. Int J Biomed Imaging. 2012;2012:26. 16. Kawada K, Hasegawa S, Hida K, et al. Risk factors for anastomotic leakage after laparoscopic low anterior resection with DST anastomosis. Surg Endosc. 2014;28:2988e2995. 17. Holm C, Tegeler J, Mayr M, et al. Monitoring free flaps using laser-induced fluorescence of indocyanine green: a preliminary experience. Micorsurgery. 2002;22:278e287. 18. Hutteman M, van der Vorst JR, Mieog JS, et al. Near-infrared fluorescence imaging in patients undergoing pancreaticoduodenectomy. Eur Surg Res. 2011;47:90e97. 19. Rodriguez-Hernandez A, Lawton MT. Flash fluorescence with indocyanine green videoangiography to identify the recipient artery for bypass with distal middle cerebral artery aneurysms: operative imaging. Neurosurgery. 2012;70:209e220.
ogino et al risk factor of anastomotic hypoperfusion
20. Shimada Y, Okumura T, Nagata T, et al. Usefulness of blood supply visualization by indocyanine green fluorescence for reconstruction during esophagectomy. Esophagus. 2011;8:259e266. 21. Still J, Law E, Dawson J, et al. Evaluation of the circulation of reconstructive flaps using laser-induced fluorescence of indocyanine green. Ann Plast Surg. 1999;42:266e274. 22. Waseda K, Ako J, Hasegawa T, et al. Intraoperative fluorescence imaging system for on-site assessment of offpump coronary artery bypass graft. JACC Cardiovasc Imaging. 2009;2:604e612. 23. Ris F, Liot E, Buchs NC, et al. Multicenter phase II trial of nearinfrared imaging in elective colorectal surgery. Br J Surg. 2018;105:1359e1367.
271
24. Boni L, Fingerhut A, Marzorati A, Rausei S, Dionigi G, Cassinotti E. Indocyanine green fluorescence angiography during laparoscopic low anterior resection: results of a casematched study. Surg Endosc. 2017;31:1836e1840. 25. Kin C, Vo H, Welton L, Welton M. Equivocal effect of intraoperative fluorescence angiography on colorectal anastomotic leaks. Dis Colon Rectum. 2015;58:582e587. 26. Wada T, Kawada K, Takahashi R, et al. ICG fluorescence imaging for quantitative evaluation of colonic perfusion in laparoscopic colorectal surgery. Surg Endosc. 2017;10:4184e4193. 27. Ogino T, Okuyama M, Hata T, et al. Evaluation of blood flow on the remnant distal bowel during left-sided colectomy. World J Surg Oncol. 2018;16:188.
Available online at www.sciencedirect.com
ScienceDirect journal homepage: www.JournalofSurgicalResearch.com
The Risk Factor of Anastomotic Hypoperfusion in Colorectal Surgery Takayuki Ogino, MD, PhD,a,b,* Tomoki Hata, MD,a Junji Kawada, MD, PhD,a Miho Okano, MD, PhD,a Yongkook Kim, MD, PhD,a Masaki Okuyama, MD, PhD,a and Toshimasa Tsujinaka, MD, PhDa a b
Department of Surgery, Kaizuka City Hospital, Osaka, Japan Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan
article info
abstract
Article history:
Background: Inadequate blood flow is an important risk factor for anastomotic leakage.
Received 29 March 2019
Indocyanine green (ICG) fluorescence imaging allows intraoperative assessment of intes-
Received in revised form
tinal blood flow. This study determined the risk factor of anastomotic hypoperfusion in
4 May 2019
colorectal surgery using ICG fluorescence imaging.
Accepted 14 June 2019
Methods: This study included 74 consecutive patients who underwent colorectal surgery
Available online xxx
between April 2017 and March 2018. ICG was injected intravenously after dividing the mesentery and central vessels along the planned transection line, but before completing
Keywords:
the anastomosis. Intraoperative blood flow was evaluated using ICG fluorescence imaging.
Hypoperfusion
With regard to the patient-, tumor-, and surgery-related factors, anastomotic perfusion
Colorectal surgery
was evaluated based on the changed transection line and prolonged (more than 60 s)
ICG fluorescence imaging
perfusion time.
Anticoagulation therapy
Results: Intraoperative ICG fluorescence imaging was performed in all patients, and no
Anastomotic leakage
adverse events were associated with ICG injection. Based on the perfusion assessment, we changed the transection line in six patients (8.1%). The prolonged perfusion time was observed in nine patients (12.2%). The postoperative course was uneventful in 63 (85.1%) patients, but one patient (1.4%) had postoperative anastomotic leakage. The changed transection line was significantly associated with anticoagulation therapy (P ¼ 0.029). Wellknown risk factors, including surgical site, sex, smoking, blood loss, operative time, and preoperative chemoradiotherapy, were not related to the changed transection line. Prolonged ICG perfusion time was not associated with any patient-, tumor-, or surgery-related factors. Conclusions: The evaluation of intraoperative blood flow using ICG fluorescence imaging may be able to detect anastomotic hypoperfusion, and anticoagulation therapy is a risk factor of anastomotic hypoperfusion in colorectal surgery. ª 2019 Elsevier Inc. All rights reserved.
* Corresponding author. Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, 2-2 E2 Yamadaoka, Suita, Osaka 565-0871, Japan. Tel.: þ81 6 6879-3251; fax: þ81 6 6879-3259. E-mail address: [email protected] (T. Ogino). 0022-4804/$ e see front matter ª 2019 Elsevier Inc. All rights reserved. https://doi.org/10.1016/j.jss.2019.06.050
266
j o u r n a l o f s u r g i c a l r e s e a r c h d e c e m b e r 2 0 1 9 ( 2 4 4 ) 2 6 5 e2 7 1
Introduction Anastomotic leakage (AL) remains a serious complication that is associated with increased perioperative mortality and length of hospital stay, as well as local cancer recurrence. Advances in surgical imaging have resulted in better clinical results in colorectal surgery.1-5 The reported incidence of AL after colorectal surgery ranges from 3% to 20%. The site of the anastomosis, sex, smoking, blood loss, operative time, preoperative chemotherapy, and preoperative radiation are associated with elevated AL rates.1,2,6-8 Inadequate blood flow can result in the failure of anastomotic healing.9 Although patient-related factors cannot be easily altered, assessment of bowel perfusion, bowel viability, and anastomotic integrity can potentially be improved. Clinical evaluations are performed based on gross findings, such as color, peristalsis, pulsation, and bleeding. However, these evaluations are subjective, and it can be difficult to quantify the actual blood supply and perfusion of the anastomosis. Therefore, objective and accurate measurements of intestinal blood flow are needed to prevent AL. In recent years, near-infrared (NIR) fluorescence imaging using indocyanine green (ICG) has been reported as a promising method for accurately evaluating intraoperative intestinal blood flow.10-14 ICG is a sterile, water-soluble, tricarbocyanine compound dye that absorbs NIR light at 800 nm and emits fluorescent light at 830 nm. After intravenous injection, ICG rapidly and extensively binds to plasma proteins and is confined to the intravascular compartment; it is cleared by the liver into bile in a few minutes. ICG contains no more than 5.0% sodium iodide and should be used with caution in patients with a history of allergy to iodides or iodinated imaging agents.14,15 Under NIR light, ICG emits fluorescence, allowing intraoperative assessment of intestinal blood flow. Anastomotic hypoperfusion could influence the AL rate. Several articles demonstrated the safety and feasibility of ICG fluorescence imaging in colorectal surgery;10-14 however, few studies have evaluated the risk factor of anastomotic hypoperfusion. Therefore, we performed a prospective, singlecenter, open-label clinical study to assess the risk factor of anastomotic hypoperfusion in colorectal surgery using ICG fluorescence imaging.
for four emergency cases. The anesthesiologist administered a 5 mg bolus of ICG intravenously after dividing the mesentery and central vessels along the planned transection line, but before completing the anastomosis. Intraoperative blood flow was evaluated using the NIR light camera system (Photodynamic Eye System, Hamamatsu Photonics, Japan). This camera was fixed 15 cm from the extracted specimen. The time from completing the ICG injection to the first visible fluorescence signal was recorded. The cutoff for prolonged perfusion was set to 60 s according to previous reports.1,4 Perfusion was assessed as inadequate or adequate on both the proximal and distal transection lines (Fig. 1), except in the case of low anterior resection (LAR) that only the proximal line was assessed. If fluorescence imaging showed hypoperfusion at the initially planned line of transection (Fig. 2), which was equivalent to the position on the cut end of the mesentery and marginal vessels, the transection line was changed to a more proximal or distal line that was determined to have normal perfusion by ICG fluorescence imaging. Anastomotic perfusion was evaluated based on the changed transection line and prolonged ICG perfusion time. In case without anastomosis such as Hartmann operation and abdominoperitoneal resection, perfusion of the proximal stumps was evaluated. All surgeries after intravenous administration of ICG were recorded and reviewed by board-certificated colorectal surgeons.
Data collection All data were prospectively collected and stored in a database, including age, sex, body mass index (BMI), American Society of Anesthesiologist score, preoperative diagnosis, history of preoperative chemotherapy and radiotherapy, steroid therapy, history of smoking or alcohol use, and complete medical history. The data were summarized as means or medians, ranges (minimum to maximum), and percentages for all patients. Intraoperative data included the site of the
Methods Patients ICG fluorescence imaging was used in consecutive patients who underwent colorectal surgery at Kaizuka City Hospital, Japan, from April 2017 to March 2018. Patients with a history of allergic hypersensitivity to ICG or iodine, as well as pregnant or lactating women, were not eligible for ICG imaging.
ICG fluorescence imaging and surgical procedure Three board-certified colorectal surgeons at our institution performed all procedures. Every patient underwent standard bowel preparation and received antibiotic prophylaxis except
Fig. 1 e Perfusion of the planned transection line was assessed by ICG fluorescence imaging. In case that the line located in normal perfusion area, the transection and anastomosis were performed at the line.
ogino et al risk factor of anastomotic hypoperfusion
Fig. 2 e The transection and anastomosis line was changed to normal perfusion area in case that ICG fluorescence imaging showed hypoperfusion at the initially planned transection line. Short dashed line indicates bowel tract.
anastomosis, vessel ligation, splenic flexure mobilization, the use of a drainage tube, intraoperative transfusions, operative time, intraoperative bleeding, the added procedure time using ICG fluorescence imaging, and the time for perfusion fluorescence after ICG injection. ICG fluorescence images were recorded and judged qualitatively in real time. Any change in the operative protocol prompted by the findings of ICG fluorescence imaging was documented. Postoperative complications (30-day morbidity and mortality) were also included in the analysis, with their severity classified according to the Clavien-Dindo classification system. Only symptomatic AL was included in the analysis. Asymptomatic AL was not considered because routine contrast enema or colonoscopy was not performed after surgery.
presented in Table 1. The median patient age was 71 y (range, 40 to 92), 40 patients (54.1%) were male and 34 patients (45.9%) were female, and the mean BMI was 20.6 kg/m2 (range, 14.7 to 28.2). Resection for colorectal cancer was the main indication for surgery (54 patients, 73.0%); in these cases, complete mesocolic excision with central vascular ligation was performed. The other patients had the following indications for surgery: five patients (6.8%) had diverticulitis, seven patients (9.5%) had bowel involvement from ovarian or pancreatic cancer, and the remaining eight patients (10.8%) had ileus. The surgical indication for ileus was suspected intestinal ischemia or intestinal ischemia that was not improved by conservative treatment with ileus tube or nasogastric tube for 2 wk. Preoperative chemoradiotherapy was performed in seven patients (9.5%), 10 patients (13.5%) had anticoagulation therapy, and three patients (4.1%) had steroid treatment. Finally, 17 patients (23.0%) had diabetes mellitus. The intraoperative data are listed in Table 2. Regarding the operative procedure, laparoscopic surgeries were performed in 49 patients (66.2%) and open surgeries were performed in 25 patients (33.8%). A loop ileostomy was performed simultaneously in eight patients (10.8%) who underwent LAR. The median operative time was 243 min (range, 58 to 1212), and the median blood loss was 60 mL (range, 3 to 3400).
ICG fluorescence imaging The perfusion assessment data are shown in Table 3. There were no adverse events associated with ICG injection, and
Table 1 e Patient characteristics (n [ 74). Age, y, median SD
The protocol for this research project was approved by the Ethics Committee of Kaizuka City Hospital. The procedures conformed to the provisions of the Declaration of Helsinki of 1995 as revised in Brazil in 2013. Written informed consent was obtained from all patients for the use of their clinical data.
71.0 10.4
Sex, n (%) Male
Ethics statement
267
Female BMI, kg/m2, mean SD
40 (54.1) 34 (45.9) 20.6 3.6
>25
11 (14.9)
25
63 (85.1)
ASA, n I/II/III
3/59/12
Indications for surgery, n (%)
Statistical analysis
Colorectal cancer Diverticulitis
All statistical analyses were conducted using GraphPad Prism software, version 5.0 b. The chi-square test and Fisher’s exact test were used to compare and analyze categorical variables. All analyses were two-tailed with P < 0.05 considered significant.
54 (73.0) 5 (6.8)
Bowel involvement from other cancer
7 (9.5)
Ileus
8 (10.8)
Preoperative chemoradiotherapy, n (%) Anticoagulation therapy, n (%)
7 (9.5) 10 (13.5)
Smoking, Brinkman index, n (%)
Results Patients A total of 74 consecutive patients who underwent colorectal surgery were analyzed. The patient characteristics are
>400
20 (27.0)
400
14 (18.9)
non-Smoker
40 (54.1)
Diabetes mellitus, n (%)
17 (23.0)
Steroids use, n (%)
3 (4.1)
Alcohol daily, n (%)
22 (29.7)
268
j o u r n a l o f s u r g i c a l r e s e a r c h d e c e m b e r 2 0 1 9 ( 2 4 4 ) 2 6 5 e2 7 1
Table 2 e Perioperative data (n [ 74). Operation, n
Table 4 e Postoperative data (n [ 74).
Laparoscopic
Open
18
12
Right-sided colectomy Left-sided colectomy Anterior resection Low anterior resection
14
4
2
2
10
3
Hartmann operation
1
4
Abdominoperineal resection
4
0
Ileostomy, n (%) Operative time, min, median SD
8 (10.8)
27 (36.5)
300, n (%)
47 (63.5)
34 (45.9)
50, n (%)
40 (54.1)
intraoperative ICG fluorescence imaging was performed in all patients. The mean time for perfusion fluorescence after ICG injection was 41.1 s (range 10 to 136). The mean added procedure time using ICG fluorescence imaging was 6.7 min (range, 2 to 16). Based on the ICG fluorescence imaging perfusion assessment, we changed the transection line in six patients (8.1%).
Postoperative morbidity ICG injection was not related to long-term or short-term morbidity. The postoperative course was uneventful in 63 (85.1%) patients, whereas the remaining 11 (14.9%) had the postoperative complications listed in Table 4. Ileus was observed in two patients, who recovered with a nasogastric tube (Clavien-Dindo grade II). Wound infection was observed in four patients, who mostly recovered with only wound washing (Clavien-Dindo grade I or II). Urinary retention was observed in four patients, who recovered with the use of a ureteral catheter or medication (Clavien-Dindo grade I or II). AL was detected in one patient (Clavien-Dindo grade IIIa); however, anastomotic hypoperfusion was not seen as a causative factor. In this case, LAR and ureteroneocystostomy were performed during the same surgery. On postoperative day 5, AL was detected after the leakage of ureteroneocystostomy that was observed on postoperative day 2. These two anastomosis sites were very close. It seemed that this AL was not caused by anastomotic hypoperfusion but rather by extended infection because of leakage associated with the ureteroneocystostomy. The median hospital stay
Table 3 e Perfusion assessment (n [ 74). 74 (100.0)
Time of procedure, min, mean SD
6.7 4.5
Time for perfusion fluorescence after ICG injection, s, mean SD
41.1 26.6
Change in the resection line, n (%)
Ileus Wound infection Urinary retention Length of hospital stay, d, median SD
IIIa: 1 II: 2 I: 3, II: 1 I: 3, II: 1 13.0 9.8
Reoperation, n
0
Mortality, n
0
was 13 d (range, 7 to 56 d). None of the patients required reoperation, and no mortality occurred.
60.0 859.1
>50, n (%)
ICG fluorescence imaging acquired, n (%)
Anastomotic leakage
243.0 169.8
>300, n (%) Blood loss (mL, median SD)
Postoperative morbidity, Clavien-Dindo grade: n
6 (8.1)
Risk factors of anastomotic hypoperfusion We investigated whether patient-, tumor-, or surgery-related factors were associated with a changed transection line or prolonged ICG perfusion time (Table 5). We classified the patients into two groups each in two categories: (1) a group with a changed transection line versus a group with no changed transection line and (2) a group in which the time for perfusion fluorescence after ICG injection was more than 60 s versus a group in which the time was less than 60 s. The changed transection line was significantly associated with anticoagulation therapy (P ¼ 0.029). No significant differences were detected according to changed versus unchanged resection line in terms of age, sex, BMI, American Society of Anesthesiologist, diabetes mellitus, smoking, alcohol, steroid use, preoperative chemoradiotherapy, operation site, operative time, and blood loss. Prolonged (more than 60 s) ICG perfusion time was not associated with any patient-, tumor-, or surgery-related factor.
Discussion Although multiple factors can contribute to AL, anastomotic hypoperfusion is a main factor. A previous report suggested that anastomotic hypoperfusion is related to late AL, whereas surgical technique is mainly related to early AL.16 Even a mechanically intact anastomosis can breakdown because of vascular insufficiency in some patients. Therefore, determining intestinal blood flow remains an area that may be able to improve outcomes by the introduction of ICG fluorescence imaging. Earlier reports found that ICG imaging can aid in surgical decision-making and improving outcomes in cardiothoracic, hepatobiliary, gastrointestinal, foregut, transplant, and plastic surgery.17-22 However, only a few studies have demonstrated the benefits of angiography in colorectal surgery.11-14,23 Previous studies demonstrated that fluorescence angiography in colorectal surgery resulted in a change in the planned transection line (5% to 40%) and reduction of AL (4% to 7%).10,11,24 Kudszus et al. reported that fluorescence angiography shortened hospital stays and reduced revision in elective resections and patients older than 70 y.12 Moreover, in a multi-institutional prospective study, PILLAR-II, fluorescence
269
ogino et al risk factor of anastomotic hypoperfusion
Table 5 e Patient-, tumor-, and surgery-related factors with potential associations with changed resection line and prolonged ICG perfusion time. Changed resection line (n ¼ 6)
Variable
n/total n
%
Age, y
P Value
Prolonged perfusion time (60 s, n ¼ 9) n/total n
%
1
0.716
75
2/22
9.1
2/22
9.1
<75
4/52
7.7
7/52
13.5
5/40
12.5
5/40
12.5
1/34
2.9
4/34
11.8
25
1/11
9.1
2/11
18.2
<25
5/63
7.9
7/63
11.1
8/62
12.9
1/12
8.3
8/64
12.5
1/10
10
Sex
0.209
Male Female 2
BMI (kg/m )
1
1
ASA
0.615
1
I/II
5/62
8.1
III
1/12
8.3
Anticoagulation therapy
1
0.029
No
3/64
4.7
Yes
3/10
30
No
4/57
7
Yes
2/17
11.8
DM
1
0.616
Smoking
0.197 5/57
8.8
4/17
23.5
4/40
10
5/34
14.7
6/52
10.9
3/22
13.6
0.209
No
5/40
12.5
Yes
1/34
2.9
Alcohol
0.724
1
No
4/52
7.7
Yes
2/22
9.1
Steroid use
1
0.227
1
No
5/71
7
9/71
12.7
Yes
1/3
33.3
0/3
0
8/67
11.9
1/7
14.3
3/17
17.6
6/57
10.5
Preoperative chemoradiotherapy
1
No
6/67
9
Yes
0/7
0
Operation site
1
0.616
Rectum
2/17
11.8
Colon
4/57
7
Operative time, s
0.421
0.406
0.273
>300
1/27
3.7
5/27
18.5
300
5/47
10.6
4/47
8.5
8.8
Blood loss, mL
1
0.494
>50
3/34
8.8
3/34
50
3/40
7.5
6/40
imaging changed surgical plans in 7.9% of cases in which it was used. In that study, the overall incidence of AL was 1.4%, and no AL occurred in the 11 patients who had a change of surgical plan.13 Ris et al. reported that ICG imaging changed the site of bowel division in 5.8% of patients with no leaks, and the AL rate was 2.4%.23 On the other hand, Kin et al. reported that fluorescence angiography did not reduce the number of colorectal ALs.25 Wada et al. reported that the difference in the
P Value
15
fluorescence signal between maximum and baseline was the most indicative factor of AL, with a sensitivity of 100% and specificity of 92.5%.26 Intraoperative evaluation of intestinal blood flow using ICG fluorescence imaging is considered to be useful because hypoperfusion could be detected even if macroscopically judged normal perfusion. However, few studies have assessed its utility and the risk factors of hypoperfusion.
270
j o u r n a l o f s u r g i c a l r e s e a r c h d e c e m b e r 2 0 1 9 ( 2 4 4 ) 2 6 5 e2 7 1
As is the case in most previous studies with 0.05 to 0.2 mg/ Kg ICG, 5 mg of intravenous ICG was used at a concentration of 2.5 mg per 1 mL water in our study.11-14,23-25 Imaging was performed successfully in all cases, and no complications were attributable to the use of ICG or the device. The incidence of changes in the bowel transection line was 8.1% due to relative ischemia observed by ICG fluorescence imaging. In this study, the changed transection line was significantly associated with anticoagulation therapy. All patients who were receiving regular anticoagulation therapy had cardiovascular disease, which indicates that the intestinal blood flow was affected by arteriosclerosis. However, well-known risk factors, such as operation site, sex, smoking, blood loss, operative time, and preoperative chemoradiotherapy, were not related to changed transection line. Prolonged perfusion time was not associated with any patient-, tumor-, or surgeryrelated factors in this study. This study has some limitations due to inherent biases associated with being a prospective single-armed study. The heterogeneous population and the small sample size did not allow us to draw definitive conclusions. The adequacy of the transection line as determined by ICG fluorescence was interpreted subjectively, which could be seen as a limitation. Therefore, it is important to quantitatively assess the ICG fluorescence signal. In addition, the intestinal blood flow needed for proper healing of an intestinal anastomosis remains unclear. Further studies are needed to address these issues, including a large multi-institutional randomized controlled study. The blood flow evaluation at not only the proximal but also the distal site is important for the success of the anastomosis.27 In this study, the distal transection line could not be evaluated during LAR because of an NIR light system for open surgery. This limitation could be solved by using a laparoscopic NIR light system. Minimal anastomotic tension is also thought to be a requirement for preventing AL, as is intestinal blood flow.16 However, no experimental studies have investigated the role of tension in intestinal anastomosis. It is difficult to design studies to evaluate anastomotic tension in a clinical setting. Although several risk factors for AL are beyond surgical control, our data demonstrate that evaluating intraoperative blood flow using ICG fluorescence imaging may be able to detect anastomotic hypoperfusion, and anticoagulation therapy is a risk factor of anastomotic hypoperfusion in colorectal surgery.
Acknowledgment Authors’ contribution: T.O. designed the work and wrote the manuscript. T.H., J.K., M.O., Y.K., M.O., and T.T. assisted with acquisition of the images and also with manuscript revision. All authors read and approved the final manuscript.
Disclosure This study received no funding. The authors declare no conflicts of interest.
references
1. Kingham TP, Pachter HL. Colonic anastomotic leak: risk factors, diagnosis, and treatment. J Am Coll Surg. 2009;208:269e278. 2. Chadi SA, Fingerhut A, Berho M, et al. Emerging trends in the etiology, prevention, and treatment of gastrointestinal anastomotic leakage. J Gastrointest Surg. 2016;20:2035e2051. 3. Mirnezami A, Mirnezami R, Chandrakumaran K, Sasapu K, Sagar P, Finan P. Increased local recurrence and reduced survival from colorectal cancer following anastomotic leak: systematic review and meta-analysis. Ann Surg. 2011;253:890e899. 4. Hirst NA, Tiernan JP, Millner PA, Jayne DG. Systematic review of methods to predict and detect anastomotic leakage in colorectal surgery. Colorectal Dis. 2014;16:95e109. 5. Hammond J, Lim S, Wan Y, Gao X, Patkar A. The burden of gastrointestinal anastomotic leaks: an evaluation of clinical and economic outcomes. J Gastrointest Surg. 2014;18:1176e1185. 6. Vallance A, Wexner S, Berho M, et al. A collaborative review of the current concepts and challenges of anastomotic leaks in colorectal surgery. Colorectal Dis. 2017;19:1e12. 7. Kang CY, Halabi WJ, Chaudhry OO, et al. Risk factors for anastomotic leakage after anterior resection for rectal cancer. JAMA Surg. 2013;148:65e71. 8. Qu H, Liu Y, Bi DS. Clinical risk factors for anastomotic leakage after laparoscopic anterior resection for rectal cancer: a systematic review and meta-analysis. Surg Endosc. 2015;29:3608e3617. 9. Sheridan WG, Lowndes RH, Young HL. Tissue oxygen tension as a predictor of colonic anastomotic healing. Dis Colon Rectum. 1987;30:867e871. 10. Hellan M, Spinoglio G, Pigazzi A, Lagares-Garcia JA. The influence of fluorescence imaging on the location of bowel transection during robotic left-sided colorectal surgery. Surg Endosc. 2014;28:1695e1702. 11. Jafari MD, Lee KH, Halabi WJ, et al. The use of indocyanine green fluorescence to assess anastomotic perfusion during robotic assisted laparoscopic rectal surgery. Surg Endosc. 2013;27:3003e3008. 12. Kudszus S, Roesel C, Schachtrupp A, Hoer JJ. Intraoperative laser fluorescence angiography in colorectal surgery: a noninvasive analysis to reduce the rate of anastomotic leakage. Langenbecks Arch Surg. 2010;395:1025e1030. 13. Jafari MD, Wexner SD, Martz JE, et al. Perfusion assessment in laparoscopic left-sided/anterior resection (PILLAR II): a multiinstitutional study. J Am Coll Surg. 2015;220:82e92. 14. Ris F, Hompes R, Cunningham C, et al. Near-infrared (NIR) perfusion angiography in minimally invasive colorectal surgery. Surg Endosc. 2014;28:2221e2226. 15. Alander JT, Kaartinen I, Laakso A, et al. A review of indocyanine green fluorescent imaging in surgery. Int J Biomed Imaging. 2012;2012:26. 16. Kawada K, Hasegawa S, Hida K, et al. Risk factors for anastomotic leakage after laparoscopic low anterior resection with DST anastomosis. Surg Endosc. 2014;28:2988e2995. 17. Holm C, Tegeler J, Mayr M, et al. Monitoring free flaps using laser-induced fluorescence of indocyanine green: a preliminary experience. Micorsurgery. 2002;22:278e287. 18. Hutteman M, van der Vorst JR, Mieog JS, et al. Near-infrared fluorescence imaging in patients undergoing pancreaticoduodenectomy. Eur Surg Res. 2011;47:90e97. 19. Rodriguez-Hernandez A, Lawton MT. Flash fluorescence with indocyanine green videoangiography to identify the recipient artery for bypass with distal middle cerebral artery aneurysms: operative imaging. Neurosurgery. 2012;70:209e220.
ogino et al risk factor of anastomotic hypoperfusion
20. Shimada Y, Okumura T, Nagata T, et al. Usefulness of blood supply visualization by indocyanine green fluorescence for reconstruction during esophagectomy. Esophagus. 2011;8:259e266. 21. Still J, Law E, Dawson J, et al. Evaluation of the circulation of reconstructive flaps using laser-induced fluorescence of indocyanine green. Ann Plast Surg. 1999;42:266e274. 22. Waseda K, Ako J, Hasegawa T, et al. Intraoperative fluorescence imaging system for on-site assessment of offpump coronary artery bypass graft. JACC Cardiovasc Imaging. 2009;2:604e612. 23. Ris F, Liot E, Buchs NC, et al. Multicenter phase II trial of nearinfrared imaging in elective colorectal surgery. Br J Surg. 2018;105:1359e1367.
271
24. Boni L, Fingerhut A, Marzorati A, Rausei S, Dionigi G, Cassinotti E. Indocyanine green fluorescence angiography during laparoscopic low anterior resection: results of a casematched study. Surg Endosc. 2017;31:1836e1840. 25. Kin C, Vo H, Welton L, Welton M. Equivocal effect of intraoperative fluorescence angiography on colorectal anastomotic leaks. Dis Colon Rectum. 2015;58:582e587. 26. Wada T, Kawada K, Takahashi R, et al. ICG fluorescence imaging for quantitative evaluation of colonic perfusion in laparoscopic colorectal surgery. Surg Endosc. 2017;10:4184e4193. 27. Ogino T, Okuyama M, Hata T, et al. Evaluation of blood flow on the remnant distal bowel during left-sided colectomy. World J Surg Oncol. 2018;16:188.