Question n.1

Which clinical scenarios and indications for the use of ICG fluorescence guided surgery in the emergency setting to improve outcomes in urgent surgical patients?

Surgical urgent scenarios:

Acute cholecystitis;

Intestinal ischemia and strangulated bowel;

Abdominal Trauma;

Prevention of anastomotic leak after intestinal/colon resection in the emergency setting;

Post-bariatric surgery emergencies.

The use of ICG cholangiography in performing cholecystectomy for acute cholecystitis.

Statement 1

ICG cholangiography is useful to achieve an adequate visualization of the biliary structures during cholecystectomy for acute cholecystitis, decreasing the operative time, conversion rate to open technique and negative outcomes [QoE C].

Recommendation 1

The WSES Panel of Experts recommends the use of ICG cholangiography that allows the correct and real-time visualisation of the extra-hepatic biliary tree anatomy during laparoscopic cholecystectomies for severe cholecystitis as it can reduce the rate of bile ducts injury and conversion to open surgery in the emergency setting in selected patients, when skills and equipments are available [Strong recommendation based on a low level evidence 1C].

Summary of evidence and discussion

Laparoscopic cholecystectomy (LC) is the golden standard treatment for acute cholecystitis. The rate of iatrogenic biliary duct injuries reported in literature is around 4% after acute cholecystitis and a significant cause of morbidity after LC [22,23,24,25,26,27].

Conventional intraoperative cholangiography (CC) was often advocated as a valid tool to visualise the biliary anatomy because it is faster, do not expose patient to ionizing radiation and can be performed and superimposed to conventional laparoscopic view during Calot’s triangle dissection.

CC disadvantages are the increased operative time and operating theatre occupation to perform a good dissection of gallbladder infundibulum and cystic duct; to place the catheter and administer the contrast; to require radiological equipment and staff; to increase the risk of ionising radiation exposure in OR and costs [22, 28, 29].

ICG cholangiography showed to support surgeons in intra-operative decision making for difficult cholecystectomy in allowing to better visualise the biliary tract and decreasing biliary injuries [9].

Unfortunately, the quality of available data on the use of ICG in the emergency setting are poor and based on single centers experiences and case-series [17, 30,31,32,33,34,35].

Vlek et al. have investigated in a systematic review the outcomes correlated to the use of near-infrared imaging using ICG for the visualization of the cystic duct and the extra-hepatic biliary tract. Nineteen studies were selected with a total of 772 patients. Results suggest that the use of the near-infrared imaging with ICG technique provides good overall visualization rates of the cystic duct, common bile duct, common hepatic duct and cystic duct junction prior to and following dissection of Calot’s triangle [36].

Di Maggio et al. [14] reported a single center experience with ICG cholangiography in performing emergency cholecystectomies and showed that the implementation of ICG cholangiography may decrease the conversion rate to open surgery and without any iatrogenic damage to the bile duct. The comparison between the ICG group and the standard LC group showed that operating time was significantly shorter in the ICG group, and post-operative length of stay was slightly higher in the standard LC group, although this was not statistically significant. Their study also showed how ICG cholangiography increased the confidence of the operating surgeon in performing laparoscopic emergency cholecystectomies for acute cholecystitis even outside the 72 h window of safety.

A single centre randomized controlled trial by She et al. [37] compared two groups of patients: conventional LC and LC with ICG cholangiography. A total of 92 patients were enrolled in the study (46 patients in each arm). The two arms of the study were comparable in all perioperative parameters. Both arms had an 8.7% conversion rate and median operative time was 140.5 min in conventional LC and 149.5 min in ICG-LC. Complication rate was 15.2% in the former and 10.9% in the latter and both had a 2.2% bile leakage rate. The median hospital stay was 3.5d in the former and 4.0d in the latter. Authors concluded that the use of ICG cholangiography did not make any difference in complication rate or conversion rate [37]. Limits of this study are the small number of patients enrolled, thus it may be underpowered to correctly identify a difference in bile duct injury rate. Furthermore, even though the difference in complications rate did not reach a statistic significance, the difference of approximately 5% should not be underestimated and should be further investigated.

Data showed that ICG cholangiography may be helpful in cholecystectomies for severe cholecystitis and could be used as an intraoperative tool providing good visualization of the biliary structures during LC. However, future researches are necessary for optimization and standardization of the near-infrared ICG technique.

The use of ICG angiography in managing intestinal ischemia and strangulated bowel.

Statement 1.1

ICG angiography may be performed safely in the emergency setting and it is a useful tool to evaluate the intestinal perfusion patterns in the setting of acute intestinal ischemia and strangulated bowel. Case series and retrospective studies reported that intestinal perfusion is visualized adequately in the most of cases [QoE C].

Recommandation 1.1

The WSES Panel of Experts recommends the use of ICG angiography to guide intra-operative decision-making in patients presenting with non-occlusive mesenteric ischemia, occlusive mesenteric ischemia and strangulated bowel in order to evaluate the intestinal blood flow and bowel viability and accurately define resection margins and anastomosis, when it is available [Strong recommendation based on a low level evidence 1C].

Summary of evidence and discussion

The intra-operative application of ICG angiography was reported to guide the identification of the optimal resection site and help estimate the blood supply of visceral anastomosis in both upper GI and colorectal surgery. The rationale behind the fluorescence angiography is that the fluorescence dye, upon systemic injection, should reach and highlight only vascularized areas [38].

Non-occlusive mesenteric ischemia

Non-occlusive mesenteric ischemia (NOMI) which can lead to multifocal and segmental intestinal necrosis without demonstrable occlusion in the main mesenteric artery, is associated with extremely high mortality rates [39]. NOMI is caused by severe vasoconstriction in the setting of peripheral hypoperfusion and clinical diagnosis is difficult. Surgical exploration and bowel resection are often required in this clinical scenario and intraoperative evaluation of intestinal perfusion is subjective and challenging [40, 41]

ICG angiography could be extremely helpful for the surgical management of NOMI. In fact, there is often a discrepancy between surgical surgeon’s eye assessment and fluorescence angiography, which may help to define resection margins more accurately and thus support surgical decision-making [42,43,44,45].

Sheridan et al. reported [42] that the accuracy of prediction of intestinal viability using clinical criteria, such us intestinal colour, arterial perfusion and peristalsis was only 57.7%. They measured tissue oxygen tension using miniaturised polarographic oxygen electrode in 134 segment of rats small intestine of varying degrees of ischaemia. Histological examination revealed that most of the specimens (n = 111) were potentially viable, as evidenced by no or minimal damage. The use of clinical criteria alone correctly identified all 23 histologically compromised segments. Of the 111 histologically non-compromised segments, however, only 40 (36%) were felt to be viable using clinical parameters [42].

Karampinis et al. [43] in a retrospective study analysed 52 patients with acute mesenteric ischemia who underwent surgical exploration with the use of ICG fluorescence angiography. Intraoperative macroscopic assessment of perfusion was compared with the ICG angiography results. In 18 cases (34.6%), ICG fluorescence angiography provided information that was supplemental to macroscopic evaluation, but most patients did not survive to postoperative course. However, in six of those cases (11.5%), ICG angiography led to a major change in operative strategy resulting in a significant clinical benefit for those patients. For two cases ICG fluorescence produced false negative results [43].

NOMI remains a problematic issue with high mortality. Urgent treatment of the underlying causes, often associated with extended intestinal resections to remove the affected tissue, is necessary to stabilise the patient. Despite the high mortality associated with mesenteric ischemia, no real progress has been made in improving the survival of those patients in the last decade and the number of clinical trials looking at innovative approaches in diagnostics and treatment remains limited [44, 45]. ICG fluorescence angiography can be performed and is a useful technical adjunct in evaluating for intestinal vascularization patterns in the setting of acute intestinal ischemia. ICG angiography could be performed without complication and intestinal perfusion is visualized adequately in the most of cases [43].

Strangulated bowel and occlusive mesenteric ischemia

During surgery for strangulated bowel or occlusive mesenteric ischemia, the viability of the bowel or intestinal loops is evaluated after treatment of the strangulation or vascular occlusion. In case of perforation, necrosis and irreversible ischemia, bowel resection is required. When bowel viability is doubtful, deciding on bowel resection and its extension, or preservation, is a difficult task and there are no established standards for decision making. The colour of the bowel, the presence or absence of peristalsis, the temperature of the intestine compared with that of the healthy part and the presence or absence of arterial pulsations in the mesentery are observed visually and tactilely. However, these assessment methods have poor sensibility and reproducibility, as reported earlier [46, 47], and are limited in a laparoscopic approach. During laparoscopic surgery, ICG angiography and near-infrared observation cameras enable intestinal blood flow evaluation [6, 48,49,50,51,52,53,54,55,56]. The use of ICG angiography can be performed also in the open approach to improve surgical outcomes. When resection is required, the bowel resection line can be set to the demarcation line of ICG angiography; this enables safe anastomosis with maximum bowel preservation [15].

Ryu et al. [15] investigated whether ICG angiography is an effective alternative to surgeon’s palpation. They enrolled 38 patients who underwent emergency surgery for strangulated bowel obstruction. Two groups were compared: (I) the ICG + group, in which ICG was used during laparoscopic surgery, and (II) the ICG—group, in which palpation without ICG was used during open surgery. Although there were fewer intestinal resections in the ICG + group, the rate of pathological necrosis of the removed specimens tended to be high, and there were no complications due to ineligibility in the intestinal preservation group. In the ICG − group, the demarcation line was not distinct under normal light observation, and bowel resection was performed slightly more carefully for safety.

Guerra et al. [57] analysed 71 patients with acute small bowel obstruction who received surgery via a laparoscopic approach. They concluded that the selective use of ICG angiography provides a direct, objective tool for assessing bowel viability and supports the surgeon in the intraoperative decision making. Compared with other methods for assessing bowel viability, ICG angiography requires only a dedicated camera and can be done in no more than 2–3 min.

In conclusion, the utility of ICG angiography in the laparoscopic management of bowel strangulation or occlusive mesenteric ischemia is threefold. Firstly, it allows recognition of the need for intestinal resection and its precise extent. Secondly, it may widen the proportion of procedures which can be completed in a minimally invasive fashion and finally, intra-operative FA may have a role in aiding the decision-making process of any emergency surgeon, regardless of his/her personal expertise. ICG is in fact a safe and reproducible adjunct to the usual management of bowel strangulation, both in a laparoscopic or open surgery setting. Its application in selected cases provides real-time determination of bowel viability, however identifying rigorous objective methods for the interpretation of ICG angiography remains an avenue for further research [11, 58].

The use of ICG angiography in managing abdominal blunt and penetrating trauma.

Statement 1.2

In the trauma setting, the use of ICG in abdominal trauma patients undergoing surgical exploration can assist surgeons in assessing the bowel viability in case of mesenteric lacerations and hematomas, and in deciding to resect or preserve small bowel and to define the extent of the resection when necessary [QeE C].

Recommendation 1.2

The WSES Panel of Experts suggests considering the use of ICG angiography in the trauma setting to assess the blood perfusion in a high-risk intestinal segment in the presence of mesenteric lacerations and hematomas in order to guide surgeons in the decision making for the appropriate repair, when it is available and faisible, in hemodynamically stable patients. Moreover, ICG angiography is useful in properly assessing the viability of the anastomotic edges and in visualising ischemic intestinal segment apparently presenting blood supply, preventing postoperative complications and planned surgical second look [Moderate recommendation based on low level evidence 2C].

Summary of evidence and discussion

In case of abdominal trauma, ICG fluorescence could be used both during open or laparoscopic surgical exploration. In the experience of Afifi’s group, ICG fluorescence was a useful instant tool in assessing and determining bowel perfusion in trauma patients, because it helps to assess the blood perfusion in a high-risk segment of the bowel with mesenteric lacerations, and thus, guides surgeon in the decision making for the appropriate repair [59]. Moreover, it is useful in properly assessing the viability of the anastomotic edges and in visualise ischemic intestinal segment apparently presenting blood supply, preventing postoperative complications and planned surgical second look [59,60,61,62,63].

The use of intraoperative fluorescent angiography was used also in war-related trauma, to evaluate tissues perfusion and it was reported that fluorescence angiography can improve the intraoperative management of patients presenting bowel injuries [64].

The use of ICG fluoroscopy in patients with abdominal trauma seems to be is feasible and useful [59], but the quality of available studies in this setting does not allow to make a recommendation.

ICG angiography and the prevention of anastomotic leak in the emergency setting.

Statement 1.3

The use of ICG fluorescence angiography may help surgeons in preventing anastomotic leakage, assessing vascular perfusion of the intestinal anastomosis [QoE C].

Recommendation 1.3

The WSES panel of Experts recommends to consider the use of ICG fluorescence angiography to assess the quality of perfusion at the site of intestinal anastomosis to prevent anastomotic leakage after emergency intestinal resection, when it is available [Strong recommendation based on low level evidence 1C].

Summary of evidence and discussion

Anastomotic leakage (AL) represents one of the most dreadful complications in general surgery and is associated with significant morbidity and mortality. Al etiology is multifactorial, and hypoperfussion is a key factor in the pathogenesis [60,61,62,63,64]. Adequate vascular perfusion of the anastomotic site is essential to prevent it. Near infrared (NIR) imaging using ICG is useful for the objective assessment of vascular perfusion [65]. Often patients undergoing bowel resection in an acute care or emergency setting have peritonitis, sepsis or septic shock, haemodynamic instability, and increased mortality and morbidity rates [66,67,68,69] when compared to elective resection. All these factors also impair bowel perfusion and are recognised as risk factors for AL.

The time required for ICG fluorescence emission was associated with AL at Hagiwara et al. study. Among 217 patients, AL occurred in 21 patients. The median time from ICG administration to maximum fluorescence emission was 32 s in the AL group and 28 in the non-AL group (p < 0.001) [70]

Surgical intervention for hollow viscus injury are associated with several complications. Anastomotic leakage, after intestinal resection, especially colo-colic or colorectal anastomosis, is one of the most serious and potentially life-threatening post-operative complications [71, 72].

One technique commonly used to assess regional intestinal vascular perfusion is subjective clinical assessment by the surgeon, including evaluation of the colour of the serosa and mucosa, bleeding at the bowel edge, pulsation of the mesenteric vessels, and bowel peristalsis. However, the accuracy of this method is limited as it is strongly influenced by the surgeon’s personal experience and other external factors [73]. In contrast, NIR-ICG is useful for the objective assessment of vascular perfusion. The use of this tool could increase the accuracy of assessment of vascular perfusion status and reduce complications compared to clinical assessment [74]. To our knowledge, however, there have been only case reports and rare retrospective study focusing specifically on the effectiveness of NIR-ICG to prevent complications and anastomotic leakage in a setting of emergency surgery. All the studies currently available focus on an elective setting [75,76,77,78,79,80,81,82,83,84,85,86,87,