Identification of Metastatic Lymph Nodes Using Indocyanine Green Fluorescence Imaging.

Indocyanine green (ICG) has been used to detect several types of tumors; however, its ability to detect metastatic lymph nodes (LNs) remains unclear. Our goal was to determine the feasibility of ICG in detecting metastatic LNs. We established a mouse model and evaluated the potential of ICG. The feasibility of detecting metastatic LNs was also evaluated in patients with lung or esophageal cancer, detected with computed tomography (CT) or positron-emission tomography (PET)/CT, and scheduled to undergo surgical resection. Tumors and metastatic LNs were successfully detected in the mice. In the clinical study, the efficacy of ICG was evaluated in 15 tumors and fifty-four LNs with suspected metastasis or anatomically key regional LNs. All 15 tumors were successfully detected. Among the fifty-four LNs, eleven were pathologically confirmed to have metastasis; all eleven were detected in ICG fluorescence imaging, with five in CT and seven in PET/CT. Furthermore, thirty-four LNs with no signals were pathologically confirmed as nonmetastatic. Intravenous injection of ICG may be a useful tool to detect metastatic LNs and tumors. However, ICG is not a targeting agent, and its relatively low fluorescence makes it difficult to use to detect tumors in vivo. Therefore, further studies are needed to develop contrast agents and devices that produce increased fluorescence signals.

Comparison of Two-Port and Three-Port Approaches in Robotic Lobectomy for Non-Small Cell Lung Cancer.

BACKGROUND: Robot-assisted lobectomy has been used to treat non-small cell lung cancer and usually uses 3 or 4 ports and 3 or 4 robotic arms. We recently developed a two-port approach for robotic lobectomy using three robotic arms and performed a propensity score-matched analysis to compare the feasibility of the two-port and three-port techniques. METHODS: Data on robotic lobectomy for non-small cell lung cancer were retrospectively reviewed. Patients were matched using propensity score based on age, sex, smoking, diabetes, hypertension, forced expiratory volume per 1 s, neoadjuvant chemotherapy, clinical stage, lobe involved, tumor size, and cell types. Overall, 53 and 89 patients who underwent the two-port and three-port approaches, respectively, were matched (1:1 ratio; caliper distance, 0.2). We analyzed the perioperative outcomes and postoperative pain to evaluate the feasibility and safety. RESULTS: The matched group included 37 patients each who underwent two-port and three-port robotic lobectomy. The operation time was shorter in the two-port group (P = .01). The number of lymph nodes resected (P = .70), conversion to multiport or thoracotomy (P > .99), morbidity and mortality (P = .31), drain indwelling time (P = .32), and hospital stay (P = .11) were not significantly different between the groups. The postoperative pain was less at 0-3 postoperative days (P < .01) in the two-port group. The total medical cost was not markedly increased after transitioning to the two-port technique. CONCLUSIONS: Two-port approach in robotic lobectomy is a safe and feasible alternative approach for treating non-small cell lung cancer.

Ultra-low-dose intraoperative X-ray imager for minimally invasive surgery: a pilot imaging study.

Background: With advances in surgical technology, thoracic surgeons have widely adopted minimally invasive limited-resection techniques to preserve normal tissues. However, it remains difficult to achieve in situ localization of invisible pulmonary nodules during surgery. Therefore, we proposed an in situ ultra-low-dose X-ray imaging device for intraoperative pulmonary nodule localization during minimally invasive surgeries. Methods: The proposed device features a hand-held type and consists of a carbon nanotube-based X-ray source and an intraoral dental sensor. In a preclinical study, we created pseudo pulmonary nodules using ex vivo pig lungs. Subsequently, its clinical feasibility was evaluated using ex vivo lung cancer specimens from patients with cancer who had undergone minimally invasive surgery. Results: Using the proposed device, we successfully differentiated normal and abnormal tissues from X-ray images of resected lung specimens. In addition, our proposed device only yielded an average radiation dose of 90.9 nGy for a single acquisition of X-ray images and demonstrated excellent temperature stability under consecutive X-ray irradiations. The radiation exposure of our proposed device (0.1±0.0006 µSv/h) was significantly lower than that of conventional C-arm fluoroscopy (41.5±51.8 µSv/h). In both preclinical and clinical studies, the margin of nodule shadows was clearly visualized using the proposed device. Conclusions: The proposed device substantially reduced radiation exposure to staff and patients and may allow in situ localization of pulmonary nodules. Our proposed device clearly revealed the margins of lung nodules with radiocontrast injection and showed the potential to identify solid nodules without the use of radiocontrast agents.

Fluorescence Imaging-Guided Identification of Thymic Masses Using Low-Dose Indocyanine Green.

BACKGROUND: Indocyanine green (ICG) fluorescence imaging has been used to detect many types of tumors during surgery; however, there are few studies on thymic masses and the dose and time of ICG injection have not been optimized. OBJECTIVE: We aimed to evaluate the optimal ICG injection dose and timing for detecting thymic masses during surgery. METHOD: Forty-nine consecutive patients diagnosed with thymic masses on preoperative computed tomography (CT) and scheduled to undergo thymic cystectomy or thymectomy were included. Patients were administered 1, 2, or 5 mg/kg of ICG at different times. Thymic masses were observed during and after surgery using a near-infrared fluorescence imaging system, and the fluorescence signal tumor-to-normal ratio (TNR) was analyzed. RESULTS: Among the 49 patients, 14 patients with thymic cysts showed negative fluorescence signals, 33 patients with thymoma or thymic carcinoma showed positive fluorescence signals, and 2 patients showed insufficient fluorescence signals. The diagnosis of thymic masses based on CT was correct in 32 (65%) of 49 cases; however, the differential diagnosis of thymic masses based on NIR signals was correct in 47 of 49 cases (96%), including 14 cases of thymic cysts (100%) and 33 cases of thymomas or thymic carcinomas (94%). In addition, TNR was not affected by the time or dose of ICG injection, histological type, stage, or tumor size. CONCLUSIONS: Low-dose intravenous injection of ICG at flexible time can detect thymic tumors. In addition, thymic cysts can be distinguished from thymomas or thymic carcinomas during surgery by the absence of ICG fluorescence signals.

Fluorescent and Iodized Emulsion for Preoperative Localization of Pulmonary Nodules.

OBJECTIVE: This study was conducted to develop a fluorescent iodized emulsion comprising indocyanine green (ICG) solution and lipiodol (ethiodized oil) and evaluate its feasibility for use in a clinical setting. BACKGROUND: ICG use for the preoperative localization of pulmonary nodules is limited in terms of penetration depth and diffusion. METHODS: First, fluorescent microscopy was used to investigate the distribution of ICG-lipiodol emulsions prepared using different methods. The emulsions were injected in 15 lung lobes of 3 rabbits under computed tomography fluoroscopy guidance; evaluation with imaging and radiography was conducted after thoracotomy. Subsequently, the emulsions were used to preoperatively localize 29 pulmonary nodules in 24 human subjects, and wedge resections were performed using fluorescent imaging and C-arm fluoroscopy. RESULTS: The optimal emulsion of 10% ICG and 90% lipiodol mixed through 90 passages had even distribution and the highest signal intensity under fluorescent microscopy; it also had the best consistency in the rabbit lungs, which persisted for 24 hours at the injection site. In human subjects, the mean diameter of pulmonary nodules was 0.9 ±â€Š0.4 cm, and depth from the pleura was 1.2 ± 0.8 cm. All emulsion types injected were well localized around the target nodules without any side effects or procedure-related complications. Wedge resection with minimally invasive approach was successful in all pulmonary nodules with a free resection margin. CONCLUSIONS: A fluorescent iodized emulsion prepared by mixing ICG with lipiodol enabled accurate localization and resection of pulmonary nodules.

Near-infrared fluorescent imaging with indocyanine green in rabbit and patient specimens of esophageal cancer.

BACKGROUND: We aimed to assess the possibility of detecting esophageal cancer after intravenous injection of indocyanine green (ICG) in preclinical and clinical models. METHODS: Forty-five rabbits were surgically implanted with VX2 tumors into the esophageal muscular layer 2 weeks before esophagectomy. The rabbits received intravenous injection of ICG at doses of 1, 2, or 5 mg/kg at 3, 6, 12, 24, or 48 h before surgical removal of esophagus. Twelve patients scheduled to undergo esophagectomy were also enrolled, and all received 2 mg/kg of ICG intravenously at 3, 6, 12, or 24 h before surgical removal of esophagus. The fluorescence intensity was measured in all resected specimens from the rabbits and patients using a near-infrared (NIR) fluorescence imaging system after surgery. RESULTS: Esophageal tumors were successfully established in all rabbits, and fluorescent signals were detected in all animal and patient specimens. Tumor-to-normal ratio (TNR) analysis showed that higher doses resulted in a greater TNR. Injection of at least 2 mg/kg of ICG was required for clear visualization of the tumor, and the TNR was highest at 12 h after injection. The TNR in patients was also highest at 12 h (P=0.0004), with 2 mg/kg of ICG. None of the patients had major complications following ICG injection. CONCLUSIONS: NIR fluorescence imaging can be used to visualize esophageal cancer after systemic injection of ICG. ICG at 2 mg/kg at 12 h is optimal for tumor detection. However, since the clinical trials were conducted in a small number of patients, further studies are needed in larger populations.

Fluorescence Image-Based Evaluation of Gastric Tube Perfusion during Esophagogastrostomy.

During esophagectomy and esophagogastrostomy, the prediction of anastomotic leakage relies on the operating surgeon's tactile or visual diagnosis. Therefore, anastomotic leaks are relatively unpredictable, and new intraoperative evaluation methods or tools are essential. A fluorescence imaging system enables visualization over a wide region of interest, and provides intuitive information on perfusion intraoperatively. Surgeons can choose the best anastomotic site of the gastric tube based on fluorescence images in real time during surgery. This technology provides better surgical outcomes when used with an optimal injection dose and timing of indocyanine green.

Levels of Extracellular Vesicles in Pulmonary and Peripheral Blood Correlate with Stages of Lung Cancer Patients.

BACKGROUND: The extracellular vesicle (EV) concentration is known to be higher in cancer patients than in healthy individuals. Herein, we report that EV levels differ in the tumor-draining pulmonary vein blood and the peripheral blood of animal models and human subjects at different pathological stages of lung cancer. METHODS: Ten rabbits and 40 humans formed the study cohorts. Blood was collected from the peripheral vein of members of all groups. Pulmonary blood was collected intraoperatively from all groups except for the healthy human controls. Quantitative analysis of EV levels was performed using a nanoparticle tracking assay, a CD63 enzyme-linked immunosorbent assay, and western blotting. RESULTS: The EV levels in the peripheral blood of animals and patients with lung cancer were higher than those in the peripheral blood of healthy controls (p < 0.01 and p < 0.001, respectively). Moreover, for both animals and patients with lung cancer, the EV levels in the pulmonary blood were significantly higher than those in the preoperative peripheral blood (p < 0.01 and p < 0.0001, respectively). In patients, the pathological stages of lung cancer showed a higher correlation with the pulmonary EV levels than the peripheral EV levels. CONCLUSIONS: EV levels increased with increasing lung cancer grade, and this trend was more prominent in the pulmonary blood than in the peripheral blood.

Evaluation of Intraoperative Near-Infrared Fluorescence Visualization of the Lung Tumor Margin With Indocyanine Green Inhalation.

Importance: Identification of the tumor margin during surgery is important for precise minimal resection of lung tumors. Intravenous injection of indocyanine green (ICG) has several limitations when used for intraoperative visualization of lung cancer. Objectives: To describe a technique for intraoperative visualization of lung tumor margin using ICG inhalation and evaluate the clinical applicability of the technique in mouse and rabbit lung tumor models as well as lung specimens of patients with lung tumors. Design, Setting, and Participants: In lung tumor models of both mice and rabbits, the distribution of inhaled ICG in the lung tumor margin was investigated in vivo and ex vivo using a near-infrared imaging system. Lung tumor margin detection via inhalation of ICG was evaluated by comparing the results obtained with those of the intravenous injection method (n = 32, each time point for 4 mice). Based on preclinical data, use of ICG inhalation to help detect the tumor margin in patients with lung cancer was also evaluated (n = 6). This diagnostic study was conducted from May 31, 2017, to March 30, 2019. Main Outcomes and Measures: The use of tumor margin detection by inhaled ICG was evaluated by comparing the inhaled formulation with intravenous administration of ICG. Results: From 10 minutes after inhalation of ICG to 24 hours, the distribution of ICG in the lungs was significantly higher than that in other organs (signal to noise ratio in the lungs: 39 486.4; interquartile range [IQR], 36 983.74-43 592.5). Ex vivo and histologic analysis showed that, in both lung tumor models, inhaled ICG was observed throughout the healthy lung tissue but was rarely found in tumor tissue. The difference in the fluorescent signal between healthy and tumor lung tissues was associated with the mechanical airway obstruction caused by the tumor and with alveolar macrophage uptake of the inhaled ICG in healthy tissues. Inhalation at a 20-fold lower dose of ICG had a 2-fold higher efficiency for tumor margin detection than did the intravenous injection (2.9; IQR, 2.7-3.2; P < .001). Conclusions and Relevance: The results of this study suggest that lung-specific inhalation delivery of ICG is feasible and may be useful for the intraoperative visualization of lung tumor margin in clinical practice.

Simultaneous visualization of pulmonary nodules and intersegmental planes on fluorescent images in pulmonary segmentectomy.

OBJECTIVES: The technique of simultaneously visualizing pulmonary nodules and the intersegmental plane using fluorescent images was developed to measure the distance between them intraoperatively. METHODS: Patients who underwent pulmonary segmentectomy were consecutively included in this study between March 2016 and July 2019. Computed tomography or electromagnetic bronchoscopy-guided localization with indocyanine green-lipiodol emulsion was performed on the day of surgery. In the middle of the surgery, after dividing the segmental artery, vein and bronchus to a targeted segment, 0.3-0.5 mg/kg of indocyanine green was injected intravenously. RESULTS: In total, 31 patients (17 men and 14 women with a mean age of 63.2 ± 9.8 years) were included in this study. The mean size and depth of the nodules were 1.2 ± 0.5 (range 0.3-2.5) cm and 16.4 ± 9.9 (range 1.0-42.0) mm, respectively. Pulmonary nodules and intersegmental plane of all the patients were visualized using a fluorescent thoracoscope. The resection margins were more than the size of the tumour or were 2 (mean 2.4 ± 1.2) cm in size in all patients except one. The resection margin of this patient looked sufficient on the intraoperative view. However, adenocarcinoma in situ at the resection margin was identified based on the pathological report. The mean duration of the operation was 168.7 ± 53.3 min, and the chest tube was removed on an average of 4.7 ± 1.8 days after surgery in all patients. CONCLUSIONS: The dual visualization technique using indocyanine green could facilitate an easier measurement of the distance between pulmonary nodules and the intersegmental plane during pulmonary segmentectomy.

Subxiphoid approach for robotic single-site-assisted thymectomy.

OBJECTIVES: We previously reported a transthoracic approach using the da Vinci Single-Site™ platform. This study describes the outcomes of robotic single-site thymectomy via a subxiphoid approach based on our previous experiences. METHODS: This study included patients, who underwent single-site robotic thymectomy via the subxiphoid approach between September 2018 and October 2019. A 3- to 4-cm vertical incision was made over the subxiphoid area, and the Lapsingle port with CO2 gas was introduced. After docking at the single site, a 5-mm curved cannula, 5-mm cardiere grasper and Maryland bipolar forceps or permanent cautery hook was inserted. The single-site robotic platform was used to conduct all surgical procedures except the dissection around the inferior portion of the thymic tissue performed via a thoracoscopic approach through the same incision. RESULTS: Overall, 13 patients, including 2 with myasthenia gravis, were enrolled. The mean duration of the surgery and chest drainage were 167.3 ± 52.8 (range 73-253) min and 2.2 ± 0.9 (range 1-5) days, respectively. All surgeries were successfully completed without conversion to an open surgery, and there were no major post-surgical complications. The diagnoses based on histopathology included thymoma in 10 patients, thymolipoma in 2 patients and atypical carcinoid tumour in 1 patient with free resection margin. CONCLUSIONS: This study demonstrated that robotic single-site-assisted thymectomy via the subxiphoid approach is a safe and technically feasible procedure. Although this initial series comprised relatively simple cases, more advanced and complex procedures can soon be performed with the advent of single-port robotic platform.

A single-port video-assisted thoracoscopic surgery with CO2 insufflation for traumatic diaphragmatic hernia.

In this article, we present 2 cases with successful reduction of herniated organs and repair of a ruptured diaphragm through a single-port video-assisted thoracoscopic surgery (VATS) approach using CO2 gas insufflation in haemodynamically stable patients. A CO2 insufflation was useful to push the diaphragm down and aided in reducing the size of the herniated organ. This approach did not cause damage to the herniated organs and no additional instrument or assistant was required. Thus, CO2 insufflation makes the single-port VATS procedure easier even in haemodynamically stable trauma patients.

Initial Experiences With Robotic Single-Site Thoracic Surgery for Mediastinal Masses.

BACKGROUND: The da Vinci Single-Site platform (Intuitive Surgical, Mountain View, CA) has been applied in many fields of surgery, but use of this single-site platform in thoracic surgery has not been reported. This study reported our experiences and surgical outcomes with robotic single-site surgery in the field of thoracic surgery. METHODS: We retrospectively reviewed 14 patients who underwent robotic single-site thoracic surgery at 2 different institutions. RESULTS: All 14 cases were successfully completed, without conversion to conventional multiport robotic surgery. The most frequent diagnoses were thymic cyst (n = 4) and pericardial cyst (n = 3). The median largest mass size was 4.1 cm (range, 2.0 to 6.5 cm). The median operation time was 105 minutes (range, 27 to 185 minutes). After the operation, pleural effusion occurred in 1 patient (case 7) on the side on which the operation was performed but was managed with conservative treatment. The median duration of chest tube stay was 2 days (range, 1 to 3 days), and hospital stay was 4 days (range, 3 to 11 days). The median peak pain score after the operation was 3 (range, 1 to 7). Compared with thoracoscopic single-port surgery, robotic single-site thoracic surgery showed a longer operative time and higher cost. CONCLUSIONS: This study demonstrated that robotic single-site thoracic surgery for mediastinal masses is a safe and feasible procedure. Although this study reports the initial series and the cases were relatively simple, more advanced and complex procedures could be done with the advent of new technology in the near future.

Comparison of additional minocycline versus iodopovidone pleurodesis during video-assisted thoracoscopic bleb resection for primary spontaneous pneumothorax: a propensity score-matched analysis.

BACKGROUND: The optimal chemical agent for additional pleurodesis during video-assisted thoracoscopic surgery (VATS) bleb resection in primary spontaneous pneumothorax (PSP) remains controversial. We compared the efficacy and safety of iodopovidone with those of minocycline for additional chemical pleurodesis during VATS bleb resection. METHODS: Of 332 patients who underwent VATS bleb resection, 299 patients diagnosed with PSP were enrolled in this study. The patients were divided into two groups according to the chemical agents used for additional pleurodesis (iodopovidone versus minocycline). Propensity score matching was performed on the basis of the preoperative clinical parameters. Postoperative complications, chest tube indwelling time, postoperative hospital stay, and recurrence rate were compared between the two groups. RESULTS: The median duration of follow-up was 14 months (range, 1-94 months). After propensity score matching, 94 patients from the iodopovidone group and 94 patients from the minocycline group were matched. The perioperative outcomes, including fever, prolonged air-leak, prolonged-effusion, postoperative bed-side pleurodesis, and rehospitalization because of complications, were not significantly different between the two groups. However, the amount of drainage during the first two postoperative days, duration of chest tube indwelling, and duration of hospitalization were significantly shorter in the minocycline group (P<0.001). CONCLUSIONS: This study confirmed the safety of both minocycline and iodopovidone for additional pleurodesis. However, we carefully recommend minocycline over iodopovidone for pleurodesis because of faster postoperative recovery.

CO2 during single incisional thoracoscopic bleb resection with two-lung ventilation.

BACKGROUND: CO2 insufflation could provide a better surgical field during single-incision thoracoscopic surgery (SITS) with small tidal two-lung ventilation (ST-TLV). Here we compared the surgical field and physiological effects of ST-TLV with and without CO2 during SITS. METHODS: Patients underwent scheduled SITS bullectomy. Surgery under ST-TLV general anesthesia performed without CO2 (group NC) or with CO2 insufflation (group C). The surgical field was graded at thoracoscope introduction and at bulla resection as follows: good (more than half of the 1st rib visible; bleb easily grasped with the stapler), fair (less than half of the 1st rib visible; some manipulation needed to grasp the bleb with the stapler), or poor (1st rib non-visible; bleb ungraspable). Vital signs, arterial blood gas analysis (ABGA), and mechanical ventilation parameters, postoperative chest tube indwelling duration, length of hospital stays, and complications were recorded. RESULTS: A total of 80 patients were ultimately included. The surgical field at thoracoscope introduction was better in group C (P=0.022). However, at bleb resection, the surgical fields did not differ (P=0.172). The operation time was significantly longer in group C (P=0.019) and anesthesia recovery time was not different (P=0.369). During the CO2 insufflation, the airway pressure was higher in group C (P=0.009). Mean PaCO2 was significantly higher (P=0.012) and mean PaO2 was significantly lower (P=0.024) in group C, but both values were within the physiologically normal range. Postoperative chest tube indwelling duration and length of hospital stays were not statistically different (P=0.234 and 0.085 respectively). Postoperative complication frequencies were similar (12.5% for group NC, 10.0% for group C, P=0.723). CONCLUSIONS: SITS with CO2 insufflation during ST-TLV did not produce a superior surgical field except at the beginning of surgery. CO2 insufflation required more time and resulted in higher mean PaCO2 and peak airway pressure.

Application of a three-dimensional video system in the training for uniportal thoracoscopic surgery.

BACKGROUND: Three-dimensional (3D) video systems offer better depth perception and are associated with improved performance during endoscopic or robotic surgery. We compared the impact of a 3D video system with a two-dimensional (2D) video system on a simulation program for uniportal thoracoscopic surgery. METHODS: We launched an endoscopic simulation program for uniportal surgery using a 3D high-definition video system for training surgeons and medical students. This program included three basic surgical skills: (I) peg transfer, (II) passing a needle through a 3-mm hole, and (III) suturing on a tailor-made skin model. We evaluated the impact of 3D vision during simulation for uniportal surgery in each task. Overall, 113 trainees (85 surgeons in training and 28 medical students) who had not experienced a 3D video system were registered in the program. The three surgical simulation skills were evaluated under 2D and 3D video systems. RESULTS: The 3D video system allowed for shorter procedural times [92 participants (80.0%) in task 1, 102 (86.4%) in task 2, and 88 (74.6%) in task 3] and improved performance. Moreover, 65 s in task 1, 145 s in task 2, and 32 s in task 3 were shortened using the 3D video system. Post-simulation survey revealed improved depth perception (n=71, 60.2%) and handling of instruments on the uniportal surgical module (n=39, 33.1%) as advantages of the 3D video system during simulation. Sixty (50.8%) trainees were not negatively affected by the use of the 3D glasses; however, 53 (44.9%) felt eye discomfort during simulation. CONCLUSIONS: We concluded that the 3D video system has potential advantages, such as improved procedure time and handling of instruments, during basic simulation of uniportal surgery for surgical trainees.

Imaging techniques for minimally invasive thoracic surgery-Korea University Guro Hospital experiences.

In this paper, we described our clinical experiences with respect to image-guided thoracic surgery, including procedures involving percutaneous injection of fluorescent dye, radiotracers, and hook wires, guided by preoperative computed tomography (CT); and transbronchial injection of fluorescent dye by using electromagnetic navigational bronchoscope technology. Our recent experience with the intravenous systemic injection of fluorescent dye for the intraoperative detection of pulmonary lesions and intersegmental planes are also described in this review.