Near-infrared indocyanine green fluorescent cholangiography in urgent and emergency laparoscopic cholecystectomy: a preliminary study after propensity score-matched study

Tokyo Guidelines 2018 (TG18) have established laparoscopic cholecystectomy (LC) as a safe and efficacious surgical intervention for the management of acute calculous cholecystitis (ACC). [1, 2].

However, the right identification of the biliary anatomy during LC is essential to prevent iatrogenic biliary injuries. This task can be particularly challenging in emergency settings, where inflammation and edema can impede proper anatomic assessment and identification of the common bile duct (CBD) can be difficult and associated with increased risk [3, 4].

Bile duct injury (BDI) is a known complication of LC [5], with reported rates ranging from 0.4% to 7% in elective cases, and is primarily attributed to intraoperative misidentification of the biliary anatomy [6‐8].

To mitigate this risk, the critical view of safety (CVS) approach has been proposed as a means of positive identification of the biliary anatomy during LC [9]. However, CVS can be difficult to achieve in emergency settings due to factors, such as adhesions, edema, and acute inflammation.

Recently, near-infrared fluorescence cholangiography (NIFC) has emerged as a novel technique for intraoperative mapping of the extrahepatic biliary system. This method utilizes indocyanine green (ICG) as a contrast agent, which is selectively metabolized by hepatic parenchymal cells and secreted entirely into the bile. By excitation of the ICG with a near-infrared laser, real-time assessment of the biliary system can be accomplished [8, 10].

Several studies have reported the safety and efficacy of ICG-assisted LC in elective settings for ACC [8, 11, 12]. However, the role of ICG in the emergency setting of LC remains to be fully explored through further investigation and only one study tries to investigate the role of ICG in the emergency setting of LC [13].

The primary aim of this study was to understand if the use of ICG in the emergency LC could improve the qualitative assessment of the extrahepatic biliary.

The secondary aim was to test the ICG-assisted LC in emergency setting and the complications rate compared to classic LC.

The study population included 120 patients. Of them, 48 (40%) were treated with intravenous administration of ICG. Table 1 (first column) shows the baseline characteristics of the 120 enrolled patients (65 ± 16 years of age, 54.2% female). The majority of patients had a grade 1 acute cholecystitis both for ICG and No-ICG group (75% vs 77.7%; p value 0.826) and less than a quarter had an history of cholecystitis and/or cholangitis (ICG group 20.8% vs No-ICG group 22.2%; p value 0.065).

Regarding postoperative course, there were no statistically significant differences in terms of Dindo–Clavien score. The overall rate of intra-operative complications and post-operative complications was 4.17% and 15.8%, respectively, with non-significant difference between groups. To note, post-operative biliary duct injury tends to decrease in ICG group despite not statistical significance (p value 0.312). After surgery, the length of hospital stay is reduced in patient treated with ICG if compared to the No-ICG group (ICG group: 4 ± 2 days vs No-ICG: 6 ± 5 days; p value: 0.071).

Due to a difference in the number of patients with previous cholangitis and cholecystitis, we perform a PSM analysis, because, in our experience, this aspect could distort the anatomy and, as consequence, the data of the study.

For this reason, a 1:1 PSM cohort including 40 patients was created for each group and the baseline characteristics, comorbidities, severity grading, and operative setting were, therefore, balanced (Table 1—from column 5).

After the homogenization of the two cohorts, the intra- and post- operative complications (including vascular and biliary duct injury) rate, results changed with a highest rate of complication in the cohort with no-ICG administration. In addition, a Dindo–Clavien score \(\ge\) 3 was highest in the no-ICG group.

A univariate analysis was performed based on the variables associated with intra- and post-operative complications and biliary duct injury. In Table 2, SIRS and history of colecistitis/colangitis were associated with intra-operative complications (HR 2.050, 95% CI 0.624–6.735; p value 0,237 and HR 3.289, 95% CI 0.944–11.454; p value 0.061) and intra-operative biliary duct injury (HR12.825, 95% CI 0.006–26.895; p value 0.339 and HR 9.690, 95% CI 0.873–10.754; p value 0.064). Conversely, the use of the intra-operative ICG imaging demonstrated a protective effect against intra-operative complications and biliary duct injury. (HR 0.037, 95% CI 0.01–3.137; p value 0.337 and HR 0.039, 95% CI 0.05–4.345; p value 0.647). SIRS and history of colecistitis/colangitis were also associated with post-operative complications and biliary duct injury (Table 3). We also could define the protective role of the NIFC in the prevention of post-operative complications and biliary duct injury (HR 0.288, 95% CI 0.068–1.224; p value 0.05 and HR 0.635, 95% CI 0.069–5.801; p value 0.687).

Up to the present, studies report the use of NIFC only in elective LCs, but we are strongly convinced that it could be useful also in an emergency setting when severe inflammatory conditions may impair normal biliary anatomy and increase the risk of intra- and post-operative complications.

For those reasons, we aim to define the feasibility and safety of NIFC in the urgent/emergency setting to improve the identification of extrahepatic biliary structures and the safety dissection of the Calot’s triangle in LC.

In our cohort of ACC patients who underwent to urgent/emergency LC, NIFC could safely identify biliary structures, as well as for elective LC [20] reducing BDI.

Given the feasibility of NIFC (preoperative ICG administration and no additional equipment [21]), we can take full advantage of it, such as shorter operation time [8, 21] and the reduction of BDI.

In our series, we confirm the shorter operative time in the NIFC group compared to the conventional group.

The main findings of the present study are: (1) NIFC is associated with the reduction of intra- and post-operative complication especially for biliary duct damage; (2) NIFC is related to reduction of general complications; and, finally, (3) patient with SIRS and history of colecistitis/colangitis were exposed to an increased risk of complications and biliary duct injury.

To our knowledge, only one randomized controlled trial [13] tries to explore the effectiveness of NIFC in the urgent and emergency setting. The trial focuses on the potential role of NIFC in lowering the conversion rate or complication in LC for ACC and they did not find any significant differences between groups but only a trend in lowering complications.

With our case series of ACC patients, we specifically evaluated the incidence of intra- and post-operative complication and biliary duct injury, and our findings might be helpful to promote the routinely use on NIFC not only in elective LC but also in the urgent and emergency setting.

In literature, LC has a conversion rate ranging from 5 to 30% [22‐25]. Globally, our patients had a conversion rate lower than 4%, which is inferior to the reported range.

In our case series, overall intra- and post-operative complication rates, such as biliary injury, bile leakage, and vascular (hepatic artery or portal vein) injury, are 4.17% and 15.8% for ICG and No-ICG group, respectively, which both fall within the range of complication rates reported [25‐27].

Based on our results, a significant reduction in complications (not directly related to BDI), operative time, and length of hospital stay are leaded using NIFC; in addition, the routinely use of ICG could reduce the use of the drain.

Several limitations are needed to be discussed: (1) Considering the urgent and emergency setting, NIFC can be affected by time of ICG’s injection and amount of the ICG administered.

The best time of ICG injection is debated and several studies suggest from a minimum of 2 h to a maximum of 18 h before surgery [28, 29].

Another open question regards the optimal dosage of ICG for NIFC in an urgent and emergency setting that remains unknown.

For elective surgery, but not for acute condition, are reported doses ranged from 0.02 to 0.25 mg/kg [8, 30, 31] and the optimal time and the optimal quantitively of ICG for NIFC still need to be defined.

(2) The retrospective design and the small number of patients may not be sufficient to define the real biliary injury rate, and the statistical power of the study could be limited. The next step then is to prospectively validate the model in a multicentric study.

On the other hand, the monocentric design of our study provides a homogeneous approach in terms of a diagnosis, surgical indication, time and dosage of ICG administration.

The use of NIFC for urgent and emergency LC for ACC is not clearly superior in terms of reduction complications and biliary duct injury. It shows the trend to reduce the rate of minor intraoperative complications, the duration of surgery, and the length of in-hospital stay.

NIFC is easy to perform, does not require additional equipment and could allow surgeons to repeatedly visualize the biliary tree during LCs, simplify the Critical View of Safety in the emergency setting too.