Thoracic duct identification using three-dimensional thoracoscope versus indocyanine green fluorescence during minimally invasive esophagectomy: a retrospective cohort study

Introduction

Chyle leaks subsequent to esophagectomy are a disheartening complication associated with considerable morbidity (1). Chylothorax, resulting from thoracic duct (TD) damage, is a refractory complication following anatomical esophagectomy and it is often difficult to identify and repair. It is presumed that intraoperative visualization of the TD anatomy individually can reduce the incidence of chyle leakage.

It has been reported that near-infrared (NIR) fluorescence imaging with indocyanine green (ICG) is beneficial for identifying the injury sites of the TD and handling chylothorax. In animal experiments and early human case reports, the application of NIR fluorescence in surgical identification of the TD has been shown (2). Fluorescence imaging technology that makes use of fluorescent dyes is currently utilized in general thoracic surgery. Specifically, it is for the mapping of sentinel lymph nodes, the identification of both the pulmonary intersegmental plane and nodules, the detection of pulmonary bullous pathologies, the evaluation of anastomotic perfusion following tracheal surgeries, as well as for TD imaging related to postoperative chylothorax (3).

In the video-assisted thoracic surgery (VATS) intervention for chylothorax in humans, NIR fluorescence imaging with ICG provides highly sensitive and real-time imaging of the TD (4). This technology boosts the ability of surgeons to conduct operations and holds specific benefits. The administration of ICG by mesenteric injection enables the highlighting of the TD during esophagectomy and may represent a potential technology for the reduction of chyle leak. The use of ICG lymphangiography for identifying the TD during left lateral neck dissection has been mentioned. Identifying the TD with ICG is both technically achievable and straightforward (5). In another report, it was stated that NIR fluorescence imaging with ICG could offer highly sensitive and real-time assessment of TD and also help in determining the origin of chyle leakage. This could contribute to reducing injuries to the TD and direct the selective ligation of the TD (6). It could serve as a promising navigation tool to lower the occurrence rate of chylothorax after minimally invasive esophagectomy (MIE).

We hypothesized that ICG-guided fluorescence imaging could provide sensitive, real-time, high-resolution intraoperative imaging of TD anatomy and function to facilitate esophagectomy. Herein, a retrospective cohort study was conducted to explore the feasibility and efficacy of three-dimensional (3D) and ICG-guided fluorescent endoscopy to detect the TD during esophageal surgery. We present this article in accordance with the STROBE reporting checklist (available at https://jtd.amegroups.com/article/view/10.21037/jtd-24-947/rc).

Methods

Patients

A retrospective review was conducted on all 354 consecutive patients who received minimally invasive thoracoscopic and laparoscopic esophagectomy in the prone position in The Second Hospital of Nanjing during the period from January 2019 to August 2023.

The medical characteristics were reviewed. When the surgeon was able to clearly identify the duct, the identification of the TD was considered positive.

Inclusion criteria were as follows: (I) preoperative examinations indicating that the tumor was localized; (II) aged >18 years without gender limitation; (III) no surgical contraindication; and (IV) Ivor-Lewis or McKeown esophagectomy by the same surgery team. Exclusion criteria were as follows: (I) incomplete perioperative data; (II) patients who did not receive oral olive oil or who did not complete their superficial inguinal lymph node injections with ICG; and (III) intent preventive TD ligation. The study was conducted in accordance with the Declaration of Helsinki (as revised in 2013). The study was approved by the Ethical Committee of Nanjing Hospital Affiliated to Nanjing University of Chinese Medicine (No. 2022-LS-js009). Informed consent from each patient was collected.

ICG fluorescence NIR lymphography

ICG (Diagnogreen; Dai-Ichi Sankyo Pharma, Tokyo, Japan) at a dose of 0.5 mg/kg (maximum dose of 25 mg) was diluted in 5 mL of physiological solution and injected into the superficial lymph nodes in the bilateral inguinal region just before repositioning under the visualization of ultrasound by us. It took 1–2 minutes to administer the ICG. The VISERA ELITE II System (Olympus Medical Systems, Tokyo, Japan) or 1688 Advanced Imaging Modalities (AIM) 4 K platform (Stryker Japan K.K., Tokyo, Japan) was utilized for ICG-enhanced NIR.

The primary outcome of this study was the intraoperative TD identification rate. The secondary outcome consisted of the identification of variants of the TD as well as complications.

The patients undergoing fluorescent laparoscopy (the ICG group), after anesthesia in the surgery room, were injected via inguinal superficial lymph nodes with 0.5 mg/kg ICG (maximum dose of 25 mg) under ultrasound guidance. The patients who received 3D laparoscopy (the 3D group) orally took 2 mL/kg olive oils (maximum dose of 150 mL) at 12 hours preoperatively.

Surgery

We submit the operation plan to the operating room a day ahead. The operating room then gives us feedback on the type of thoracoscope available for the next day’s operation based on the schedule. If we are assigned a fluorescent thoracoscope, we administer preoperative injection of ICG into the patient’s superficial inguinal lymph nodes. And if we are assigned a 3D thoracoscope, patients take olive oil orally preoperatively. In the ICG group, the operations were performed with a Stryker fluorescent imaging system, which was discontinuously switched between the standard mode and the fluorescent mode during the surgery. The anatomy of TDs was checked. When the evident fluorescence leakage occurred, preventive TD ligation was applied individually (Figure 1). In the 3D group, a Karl Storz 3D high-definition imaging system was utilized. When the chyle leakage was suspected intraoperatively, preventive TD ligation was performed (Figure 2). The surgical procedures included McKeown and Ivor-Lewis MIE according to the location of the tumor.

Figure 1 The intraoperative findings in the ICG group. (A) Thoracic duct under fluorescent mode, (B) no chyle leakage observed under standard mode, (C) thoracic duct injury and fluorescence leakage were found under fluorescent mode, (D) fluorescence interruption in the thoracic duct after its ligation. ICG, indocyanine green.

Figure 2 The intraoperative findings in the 3D group. (A) Thoracic duct mutation, (B) chyle leakage was found, (C) thoracic duct ligation, (D) the chyle leakage from the thoracic duct was disappeared. 3D, three-dimensional.

Data collection

The perioperative data including the baseline features, operative time, and successful recognition of the TD, the number of preventive TD ligations, postoperative chylothorax, and thoracic drainage at postoperative day 1, 2 and 3 were collected. Meanwhile, the ICG-specified complications were also documented.

Statistical analysis

Using Statistical Package for the Social Sciences software version 23.0 for Windows (SPSS Inc., Chicago, IL, USA), statistical analysis was performed. Associations between the fluorescent group and the 3D group and baseline factors were analyzed using Chi-squared tests for categorical variables and the Mann-Whitney U test for continuous variables. P<0.05 was considered statistically significant.

Results

Patient characteristics

Initially, a total of 412 esophageal cancer patients were admitted in our hospital between January 2019 and August 2023. Twelve patients without preoperative prepositioning, 10 cases of direct open thoracotomy, 8 cases of mediastinal operations, 6 case of tubular stomach surgery via the retrosternal route, and 22 cases with incomplete data were excluded. Finally, 354 cases were enrolled, including 179 cases in the ICG group and 175 cases in the 3D group. There were no significant differences between the two groups in baseline data such as gender, age, height and weight (Table 1).

Perioperative findings

There were no significant differences between the two groups in terms of the proportions of different surgical procedures, anastomosis method, operation time, number of dissected lymph nodes, the amount of intraoperative bleeding, tumor-node-metastasis (TNM) staging and pathological type. Moreover, in terms of the time of postoperative chest tube duration and postoperative hospital stay (Table 2), the patients of the two groups had no significant differences.

TD identification and management

The TD recognition rate in the ICG fluorescent group was 98.9%, and there were 9 cases of intraoperative TD injury, 15 cases of preventive TD ligation, without postoperative occurrence of chylothorax. However, the patients in the 3D group reported a TD recognition rate of 96.0%, followed by 8 cases of intraoperative TD injury, 17 cases of preventive ligation and no postoperative chylothorax. These parameters were not significantly different between the two groups, as well as the thoracic drainage volume at the 3^rd day after the esophageal surgery (Table 3).

Postoperative complications

No mortality was recorded in this cohort. In the ICG fluorescent group, there were 7 cases of anastomotic leakage, 17 cases of pneumonia, 8 cases of hoarseness, and 1 case of gastric retention. In the 3D group, there were 7 cases of anastomotic leakage, 15 cases of pneumonia, 5 cases of hoarseness, and 1 case of cerebral infarction. Regarding the postoperative complications, no significant difference was found between the two groups (Table 2). The 14 cases of anastomotic leakage were treated with cervical dual-tube continuous irrigation and drainage as well as intestinal nutrition. All fistula openings were cured between the 14^th and the 33^rd day and all 14 patients were healed and discharged. The 32 cases of lung infection were cured by anti-infection treatment. The 13 cases of hoarseness were cured spontaneously within 1–3 months postoperatively. The patient with gastric retention received conservative treatments including gastrointestinal decompression, and he was cured after 1 month thereafter. The patient who suffered from postoperative cerebral infarction received anticoagulant and thrombolytic therapy and recovered on the 7^th day after the onset of infarction.

ICG-specified adverse reactions

All 179 patients in the fluorescence group were injected with ICG via inguinal superficial lymph nodes under the real-time guidance by ultrasound. All patients were well tolerated without allergy, pain, infection, or necrosis at the injection site.

Discussion

The study confirmed the reliability and efficacy of ICG and 3D thoracoscope during esophagectomy. ICG-based fluorescence imaging is a promising technology to decrease surgical morbidity after MIE, which is an emerging approach in cancer surgery, helps surgeons make intraoperative decisions. During esophagectomy, this technique promotes the intraoperative identification of the TD and the proximal and distal ligation by means of lymphangiography-guided injection of ICG. There are several issues that should be clarified accordingly.

Currently, fluorescence technology with ICG is utilized for visualizing lymphatic vessels, localizing tumors, performing fluorescence angiography for anastomotic evaluation, visualizing the TD, analyzing tracheal blood flow, and conducting sentinel node biopsy (7). Another report indicates that NIR fluorescence is beneficial for detecting small, non-palpable, additional tumor nodules, the sentinel lymph node, and the appropriate intersegmental plane for segmentectomies; furthermore, it can assist in visualizing the TD, smaller bullae of the lung, the phrenic nerve, or pleural nodules during thoracic surgery (8).

Fluorescence imaging, particularly using ICG, could be used for enhancing the visualization of conduit vascularity and may help reduce the incidence of anastomotic leakage faced during esophagectomy. Reportedly, the three main indications of ICG are to make the conduit vascular supply visible, to identify sentinel nodes, and to visualize the TD during esophagectomy, and this can decrease surgical morbidity such as anastomotic leak and chylothorax (9). Ultrasound-guided ICG lymphography can be performed to obtain real-time fluorescent images of the TD to identify TD during oesophagectomy (10). The identification rate of the TD, as it is reported, was 93.8% when using NIR fluorescence imaging with ICG injected subcutaneously in the inguinal area. Four patterns were found in the visible TD. Among them, 50% were in the typical pattern, 18.8% in the duplication pattern, 12.5% in the branching pattern, and 12.5% in the plexiform pattern (11). Therefore, when the TD is damaged or there’s a strong suspicion of injury, we choose to ligate it proximally at the site of injury rather than ligating the main trunk from the root.

We try to avoid prophylactic ligation of the TD because it has been demonstrated that patients without prophylactic ligation of the TD had a median survival increase of 11.5 months and a 4.1% increase in 10-year absolute survival compared to those who underwent prophylactic ligation (12) The occurrence of chylothorax is difficult to foresee because of the heterogeneity in the anatomy of the TD, therefore, the ICG may greatly improve the identification of the TD for ligation, with a favorable impact on the postoperative recovery of the patients (13).

A review reported that in the ICG group, the pooled incidence of anastomotic leakage and graft necrosis was 11.1%, and this group had less of these problems. As a result, using ICG for fluorescence imaging is a promising and safe technique to lower surgical morbidity after esophagectomy with continuity repair. ICG fluorescence angiography demonstrated a decrease in anastomotic leakage and graft necrosis (14). Feasibility of ICG lymphography for chyle fistula detection needs to be demonstrated by future studies.

Moreover, considering the administration method of the ICG, it is also reported that intra-nodal ICG injection before MIE helps to identify the TD in real-time to successfully manage a TD injury (15).

With a reported incidence of 5% to 20%, en bloc resection of the TD compartment may improve oncologic outcomes in esophagectomy for malignant esophageal diseases, yet it also raises the risk of postoperative chylothorax (16). The 3D system, as is known, offers in-depth perception and the accurate measurement of anatomical spaces when compared with the conventional two-dimensional (2D) video system. However, its advantages in MIE are unclear. When 3D endoscopy is introduced into MIE, it may be conducive to shortening the duration of thoracoscopic procedures (17). In addition, another study reported that when performing 3D MIE compared with 2D MIE, there was reduced blood loss and a higher lymph node yield, while the other intraoperative and postoperative outcomes were similar in both groups (18). Moreover, as compared with 2D thoracoscopic MIE, glasses-free 3D thoracoscopic surgery for esophageal cancer has higher safety. Through optimized surgical operations, it can perform more lymph node dissection and has higher operation efficiency (19). The limitation of MIE lies in the construction of intrathoracic anastomosis. The barbed knotless suturing technique within MIE is an efficient and safe method for constructing the esophagogastric anastomosis, and it has promising outcomes. Moreover, it is reported that when performing the anastomosis, a 3D thoracoscopic approach seems to be better than a 2D technique (20).

The limitations of this cohort study included the single-center retrospective nature and small sample. Further high-quality trials are warranted to confirm the usefulness of ICG-guided real-time imaging during esophageal surgery.

Conclusions

In summary, 3D laparoscopy and ICG-guided fluorescent thoracoscope are reliable and simplified procedures for TD identification in esophageal operations. Moreover, the ICG-fluorescent laparoscopy might be a preferred method in TD protection or ligation.

Acknowledgments

We thank all the patients and hospital staff who offered help in this study.

Funding: None.

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://jtd.amegroups.com/article/view/10.21037/jtd-24-947/rc

Data Sharing Statement: Available at https://jtd.amegroups.com/article/view/10.21037/jtd-24-947/dss

Peer Review File: Available at https://jtd.amegroups.com/article/view/10.21037/jtd-24-947/prf

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-24-947/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was conducted in accordance with the Declaration of Helsinki (as revised in 2013). The study was approved by the Ethics Committee of Nanjing Hospital Affiliated to Nanjing University of Chinese Medicine (No. 2022-LS-js009). Informed consent from each patient was collected.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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