Efficacy of different indocyanine green doses in fluorescent laparoscopic cholecystectomy: A prospective, randomized, double-blind trial.

BACKGROUND AND OBJECTIVES: Intraoperative bile duct injury is a significant complication in laparoscopic cholecystectomy (LC). Near-infrared fluorescence cholangiography (NIFC) can reduce this complication. Therefore, determining the optimal indocyanine green (ICG) dosage for effective NIFC is crucial. This study aimed to determine the optimal ICG dosage for NIFC. METHODS: This was a prospective, randomized, double-blind clinical trial at a single tertiary referral center, including 195 patients randomly assigned to three groups: lower dose (0.01 mg/BMI) ICG (n = 63), medium dose (0.02 mg/BMI) ICG (n = 68), and higher dose (0.04 mg/BMI) ICG (n = 64). Surgeon satisfaction and detection rates for seven biliary structures were compared among the three dose groups. RESULTS: Demographic parameters did not significantly differ among the groups. The medium dose (72.1%) and higher dose ICG groups (70.3%) exhibited superior visualization of the common hepatic duct compared to the lower dose group (41.3%) (p < 0.001). No differences existed between the medium and higher dose groups. Similar trends were observed for the common bile duct and cystic common bile duct junction. CONCLUSIONS: In patients undergoing fluorescent laparoscopic cholecystectomy, the 0.02 mg/BMI dose of indocyanine green demonstrated better biliary structure detection rates than the 0.01 mg/BMI dose and was non-inferior to the 0.04 mg/BMI dose.

Indocyanine green fluorescence visualizes landmark arteries for endoscopic sinus and skull base surgery.

OBJECTIVE: Landmark arteries during endoscopic sinus surgery are currently identified on the basis of anatomy, CT imaging and navigation, and Doppler flowmetry. However, the advantage of intraoperative fluorescence imaging during endoscopic sinus surgery has not been demonstrated. This study aimed to investigate whether Indocyanine Green (ICG) is useful for visualizing landmark arteries during endoscopic sinus and skull base surgery. METHODS: Eight patients who underwent endoscopic sinus and pituitary surgeries and consented to study participation were included. After planned procedures were performed as usual, landmark arteries were examined by ICG endoscope. Recorded video and preoperative CT images were analyzed for identification of five landmark arteries: anterior ethmoidal artery (AEA), posterior ethmoidal artery (PEA), internal carotid artery (ICA), sphenopalatine artery (SPA), and postnasal artery (PNA). Identification of arteries was evaluated three grades: identifiable, locatable, unrecognizable. RESULTS: Eight patients and eleven sides were evaluated. The ICG dose was 2.5 mg/body and a single shot was sufficient for evaluation. 100 % of AEA was identified (9/9 sides), 86 % of PNA (6/7 sides), 56 % of ICA (5/9 sides), and 25 % of PEA and SPA (2/8 sides). CONCLUSION: ICG could visualize landmark arteries, even thin arteries like AEA, during endoscopic sinus and skull base surgeries. Visualization was affected by thickness of bone or soft tissue above arteries, blood clots, sensitivity setting, and angle and distance of near-infrared light irradiation. ICG visualization of landmark arteries may help avoid vascular injuries during endoscopic sinus and skull base surgeries, particularly of AEA, PNA and ICA.

An indocyanine green fluorescence-guided operation for diagnosing and treating pleuroperitoneal communication.

Pleuroperitoneal communication occurs when ascites moves from the abdominal cavity to the pleural cavity via a diaphragmatic fistula. Managing large pleural fluid volumes is challenging, often requiring an operation. Identifying small diaphragmatic fistulas during the operation can be problematic, but ensuring their detection improves outcomes. This video tutorial presents a recent empirical case in which we successfully identified and closed a pleuroperitoneal contact using a thoracoscopic surgical procedure aided by indocyanine green fluorescence imaging. The patient, a 66-year-old woman, was hospitalized due to acute dyspnoea from a right thoracic pleural effusion during hepatic ascites treatment for cirrhosis. Because ascites decreased with pleural fluid drainage, surgical intervention was considered due to suspicion of a pleuroperitoneal connection. During the operation, indocyanine green was injected intraperitoneally, and near-infrared fluorescence-guided thoracoscopy pinpointed the location of the diaphragmatic fistula. The fistula was sutured and reinforced with a polyglycolic acid sheet and fibrin glue. Detecting the fistula intraoperatively is crucial to prevent recurrence, and the indocyanine green fluorescence method is a safe and effective technique for detecting small fistulas.

Laparoscopic Anatomical Cranial Sub-segmentectomy of Segment VII (S7) with Super-Selective Intra-arterial Nano-ICG Positive Staining-Guided Trans-Parenchymal Approach.

BACKGROUND: With introduction of "cone unit," which is the smallest resectable anatomical area supplied by a tertiary branch of Glissonean pedicle, more precise subsegmental anatomical resection has been proposed.1 Super-selective intra-arterial ICG staining, delivering ICG and lipiodol mixing to arterial branch using interventional radiology, has been proved feasibility especially for complicated anatomy.2-6 It was difficult to uniformly mix water-soluble ICG with lipophilic lipiodol, rendering to inconsistency development of liver segment between angiography and laparoscopy. Nano-ICG is a uniform mixing of ICG and lipiodol.7 We demonstrated an exclusive "two-step" method to perform LAR for cranial S7 via super-selective intra-arterial nano-ICG staining guidance. METHODS: A 70-year-old male was admitted. CT scan showed tumor was located in cranial S7 with 2.1*1.9 cm. Preoperative AFP was 4.66 ng/ml and PIVKA-II was 2332 mAU/ml. The liver function was Child-Pugh class A and ICG-15R was 7.8%. Given that tumor was confined to cranial S7, precise anatomical sub-segmentectomy was warranted. This study was approved by the West China Hospital, Sichuan University Ethics Committee (approval number: 2023-2327). RESULTS: The operation was performed "two step." "First step" was super-selective intra-arterial nano-ICG embolization in intervention room, while "second step" was performed in operation room. ICG demarcation line was clearly identified even after 7 hr. After full mobilization of right hemiliver, we performed transparenchymal approach to find and clamp pedicle of cranial S7 under fluorescence guidance. Operation time was 150 min with 20 ml of blood loss with uneventful course. CONCLUSIONS: Although LAR of S7 remains challenging, super-selective intra-arterial nano-ICG positive staining guidance might be a feasible and safe option.

Intraoperative trypan blue central landmark and its use in capsulotomy and capsulorhexis centration.

PURPOSE: To compare 3 capsulotomy centration methods. SETTING: Private clinic, Zlin, Czech Republic. DESIGN: Prospective, consecutive case series. METHODS: 180 eyes undergoing cataract surgery had anterior capsule staining with microfiltered 0.4% trypan blue solution before selective laser capsulotomy. The first 60 eyes (Group 1) had mydriatic dilated pupil centered capsulotomies. The next 60 eyes (Group 2) were centered on the trypan blue central landmark (TCL). The final 60 capsulotomies (Group 3) were centered on the patient fixated coaxial Purkinje reflex (CPR). Measurements between key anatomical landmarks and the TCL, CPR capsulotomies, and implanted intraocular lens (IOL) center were made. RESULTS: The TCL, observed in >94% of eyes in the study, coincided with the CPR with a displacement of <0.1 ± 0.1 mm. Group 1 capsulotomies were noticeably decentered on the IOLs by 0.3 ± 0.2 mm. The Group 2 symmetrical IOL relationship was maintained with a decentration of 0.15 ± 0.1 mm. Group 3 had a similar decentration with the IOLs with 0.15 ± 0.1 mm. Verification with IOLMaster 700 data and CALLISTO Eye System showed that the CPR and the TCL were coincident with the measured visual axis. CONCLUSIONS: The clearly visible TCL served as an alternate landmark to the patient fixated CPR, and being on the anterior capsule was not sensitive to tilt. Further patient compliance was not required. Both were superior to dilated pupil centration, to achieve symmetric IOL coverage. This has application for both capsulotomies and capsulorhexes.

A Pilot Study for Biliary Atresia Diagnosis: Fluorescent Imaging of Indocyanine Green in Stool.

BACKGROUND: Biliary atresia is the most common cause of obstructive jaundice in infants and conventional cholangiography is the current diagnostic gold standard. Fluorescent cholangiography with indocyanine green can enhance biliary tree visualization during surgery because it is exclusively excreted into the bile ducts and eventually into the intestine. Therefore, we hypothesized that indocyanine green presence in stool could confirm bile duct patency in infants. METHODS: A prospective single center cohort study was performed on infants (age ≤ 12 months) with and without jaundice after obtaining IRB approval. Indocyanine green was administered intravenously (0.1 mg/kg). Soiled diapers collected post-injection were imaged for fluorescence. RESULTS: After indocyanine green administration, fluorescence was detected in soiled diapers for control patients (n = 4, x = 14 h22 m post-injection) and jaundiced patients without biliary atresia (n = 11, x = 13 h28 m post-injection). For biliary atresia patients (n = 7), post-injection soiled diapers before and after Kasai portoenterostomy were collected. Fluorescence was not detected in stool from 6 of 7 biliary atresia patients. As a test, indocyanine green detection in stool was 97% accurate for assessing biliary patency. CONCLUSION: Fluorescent Imaging for Indocyanine Green (FIInd Green) in stool is a fast and accurate approach to assess biliary patency non-invasively in infants. LEVEL OF EVIDENCE: Level III.

Association between the arm-to-choroidal circulation time and clinical profile in patients with polypoidal choroidal vasculopathy.

PURPOSE: To investigate the association between the arm-to-choroidal circulation time (ACT) on indocyanine green angiography (IA) and clinical profile in patients with polypoidal choroidal vasculopathy (PCV). STUDY DESIGN: Single-center retrospective study. METHODS: We included 38 eyes of 38 patients with PCV diagnosed using multimodal imaging and did not undergo previous treatment. All patients were treated with monthly aflibercept injections for 3 months and treat-and-extend regimens for the subsequent 12 months. Posterior vortex vein ACT was assessed on the first visit using Heidelberg IA. The patients were divided into two groups: ACT ≥20 s (L group; eight eyes) and ACT <20 s (S group; 30 eyes). The clinical profiles before and after treatment were analyzed to assess associations with ACT. RESULTS: The mean ACT was 16.39±3.3 s (L group: 21.25±1.49 s, women:men=2:6, mean age: 77.3±6.5 years; S group: 15.10±2.17 s, women:men=7:23, mean age: 75.5±6.9 years). No significant difference was observed in the mean subfoveal choroidal thickness between the L and the S groups (176±75 µm vs. 230±79 µm, P=0.10). However, there were significant differences between the L and S groups in retinal fluid accumulation and hemorrhage recurrence (eight/eight eyes, 100% vs. 13/30 eyes, 43%, P<0.001), mean aflibercept injections (8.8±1.6 vs. 7.0±1.6, P<0.01) during the 12-month period, and the number of polypoidal lesions (1.8±0.7 vs. 1.3±0.5, P<0.05). CONCLUSION: Patients with PCV and ACT >20 s are more likely to experience exudative change recurrence in the retina during treatment because they have more polypoidal lesions.

Indocyanine green lymphography in the congenital chylothorax and chylous ascites.

BACKGROUND: The prognosis of congenital chylothorax and ascites ranges from spontaneous resolution to death, but no established examination exists to predict the prognosis. We aimed to develop a clinically useful method to evaluate lymphatic abnormalities using indocyanine green (ICG) lymphography in infants with congenital chylothorax and ascites. METHODS: We retrospectively evaluated infants with congenital chylothorax and chylous ascites who underwent ICG lymphography in our hospital between 2012 and 2022. The ICG lymphography findings was evaluated. We defined the dermal backflow in the trunk as the lymphatic flow from the end of the limb back through the lymphatic vessels on the surface of the trunk. The association between the dermal backflow in the trunk and clinical outcomes, as follows, are investigated: the duration of the drainage period, the duration of endotracheal intubation, and the length of hospital stay. RESULTS: Twenty infants had a dermal backflow in the trunk, and ten did not. Clinical outcomes in infants with and without dermal backflow in the trunk were as follows (median): the duration of the drainage period (20 vs. 0 days, p = 0.001), the duration of endotracheal intubation (12 vs. 2 days, p = 0.04), and the length of hospital stay (62 vs. 41 days, p = 0.04), respectively. In multivariate linear regression analysis adjusted for gestational age, the duration of the drainage period was correlated with the dermal backflow in the trunk [exp(B) = 2.62; p = 0.003]. CONCLUSIONS: The dermal backflow in the trunk in ICG lymphography was useful in predicting the clinical course of congenital chylothorax and ascites.

Indocyanine green (ICG)-guided robotic resection for liver adenoma: combined technologies for precision surgery.

HCA resection is crucial to prevent bleeding and malignant transformation. The aim of this study was to enhance the precision of tumor resection in hepatocellular adenoma (HCA) through the combination of intraoperative ultrasound (IOUS) and indocyanine green (ICG) fluorescence imaging. ICG was intravenously injected 24 h before surgery, enabling positive staining of HCA nodules. IOUS guided the parenchymal transection performed using the RoboLap approach. IOUS combined with ICG effectively demarcated lesions, allowing precision surgery while sparing healthy liver tissue. Intraoperative frozen examination further validated the potential of ICG to identify previously undetected lesions. The study showed promising advantages of ICG in HCA resections, potentially reducing the risk of recurrence and malignant transformation. The combined robotic and laparoscopic approach improved the feasibility of parenchymal-sparing surgery, offering a cautious assessment of HCA lesions.

Para-testicular injection of indocyanine green for laparoscopic immunofluorescence-guided lymphatic-sparing Palomo procedure: Promising preliminary results.

Lymphatic-sparing Palomo procedure with intra-testicular injection of indocyanine green (ICG) has shown good results but the injection might harm the testes. This article describes the results of twelve consecutive patients where visualization and sparing were carried out successfully with para-testicular injection of ICG. Procedural details are reported thoroughly. Early experience shows convincing results, we believe that para-testicular injection leads to equally good visualization of testicular lymphatic vessels without the risk of testicular lesions. We will continue to use para-testicular injection and encourage others to do so to increase the amount of available data, allowing for evidence-based result in the future.

Skin rejuvenation through topical application of indocyanine green with diffractive optical element mode of 785 nm picosecond laser in Asian females.

BACKGROUND: Indocyanine green (ICG) exhibits robust absorption near 800 nm. AIMS: To examine the clinical effects of combining ICG with a 785 nm picosecond laser for treating photo-aged skin. PATIENT/METHODS: A 785 nm 600 picosecond laser was used on the facial area of 16 female patients with Fitzpatrick skin type III and IV (mean age: 58.44 ± 5.24 years) after applying 0.0125% ICG cream. A total of 3000 shots were administered in diffractive optical element mode at a pulse energy of 200 mJ and frequency of 10 Hz. Hyperpigmented lesions were treated using the Zoom handpiece set at a spot size of 3-4 mm, pulse energy of 60-120 mJ, and frequency of 3-7 Hz. Patients underwent five sessions of treatment at intervals of 1-2 weeks. Wrinkles, pores and pigmented lesions were assessed at the initial assessment and 4 weeks after the final treatment using the Modified Fitzpatrick Wrinkle Scale and 10-point visual analog scale, respectively. Skin biopsy of the postauricular area was performed on two consenting patients. RESULTS: Significant improvements in wrinkles (p = 0.02), pores (p = 0.034), and hyperpigmentation (p = 0.036) were observed, along with increased patient subjective improvement. Adverse effects were transient and well-tolerated. Hematoxylin and eosin and Masson's trichrome staining revealed increased and thickened dermal collagen fibers. Immunohistochemical staining revealed increased expression of collagen I and III throughout the papillary and upper reticular dermis, along with diffuse increase of STRO-1 in the dermis. CONCLUSIONS: The combined application of a 785 nm picosecond laser and ICG yielded promising clinical outcomes for treating photo-aged skin in Asian patients with Fitzpatrick skin type III and IV.

Comparison of the perioperative outcomes of using the Firefly system with indocyanine green during robotic-assisted cystectomy with urinary diversion.

INTRODUCTION: Use of indocyanine green (ICG) with near-infrared fluorescence (NIRF) has been demonstrated to be an effective tool for intraoperative assessment of bowel and ureteric vascularity. This study aimed to evaluate the impact of ICG on postsurgical outcomes such as anastomotic bowel leak and uretero-enteric stricture formation during robot-assisted cystectomy (RAC) and intracorporeal urinary diversion (ICUD). METHODS: We identified 238 patients who underwent RAC at the University of Louisville between September 2012 and August 2021. Patients were divided into two groups based on the utilization of ICG. Demographic, perioperative outcomes, and rate of anastomotic bowel leak were compared. RESULTS: In total, 138 patients were in the ICG group and 100 patients were in the non-ICG group. More intracorporeal urinary diversions and more simple cystectomies were observed in the ICG group (p < 0.001 and p = 0.015, respectively). The ICG group patients initiated an oral diet sooner than the control group (4.9 vs. 7.1 days, p < 0.001). The mean length of stay of the ICG group was shorter than the non-ICG group (8.3 vs. 12.8 days, p < 0.001). The rate of postoperative ileus was not significantly different between cohorts. No patients in the ICG group experienced a bowel leak compared with five patients in the non-ICG group (p = 0.008). CONCLUSIONS: In our study, the use of ICG for intraoperative assessment of bowel and ureteric vascularity was associated with earlier bowel recovery and a shorter length of stay. It was also significantly correlated with a lower rate of anastomotic bowel leak.

Evaluating the effectiveness of dual dye combination of indocyanine green and carbon nanoparticles with parathyroid hormone test in preserving parathyroid gland during papillary thyroid cancer surgery: a single-center retrospective cohort study.

Preserving the integrity of parathyroid glands is crucial in papillary thyroid cancer (PTC) surgery to avoid hypoparathyroidism. In recent years, two novel dyes, activated carbon nanoparticles (CNP) and indocyanine green (ICG), have been utilized to assist in parathyroid gland identification. However, the use of CNP or ICG alone can result in extravasation of dye or excessive fluorescence of non-parathyroid tissue, which can affect the accuracy of surgical outcomes by yielding false negative or false positive results. Therefore, it is important to further optimize the application of these two dyes in surgery. We analyzed case files of 124 PTC patients who underwent routine total or near-total thyroidectomy with bilateral lymph node dissection in the central region at the Affiliated People's Hospital of Ningbo University from January to November 2022. The patients were randomly divided into three groups based on the type of intraoperative dye used. The CNP group (n = 38) received an intra-thyroidal injection of CNP dye. The ICG group (n = 42) used the ICG near-infrared fluorescence endoscopy system to show parathyroid fluorescence. The group that received a combined approach of ICG and CNP (n = 44) leveraged the advantages of both methods that allow for positive development of ICG and negative development of CNP to identify and preserve the parathyroid gland during operation. The parathyroid hormone detection reagent (PTH test method) was employed to verify the highly suspected parathyroid tissue in all three groups. We analyzed intraoperative data pertaining to intraoperative parathyroid identification, misexcision, number of autotransplantation, and postoperative hypoparathyroidism among the three groups. Compared with the ICG group and the CNP group, the combined group demonstrated more prominent advantages in identifying average the number of lower parathyroid glands (1.93 ± 0.26, p = 0.015), reducing the average numberrate of misexcision (0.45 ± 0.5, p = 0.004), and reducing the incidence of postoperative temporary hypothyroidism (3/44, p = 0.015). The combined use of ICG and CNP dual-dye with PTH test method appears to be more effective in both identifying and protecting parathyroid glands during PTC surgery.

Intraoperative visualization of cranial nerve schwannomas using second-window indocyanine green: A case series.

BACKGROUND: Second Window Indocyanine Green (SWIG) is a novel intraoperative imaging technique that uses near-infrared (NIR) light for intra-operative tumor visualization using the well-known fluorophore indocyanine green (ICG). Because schwannomas often incorporate the nerve into the encapsulated tumor and impinge on surrounding neural structures, SWIG is a promising technique to improve tumor resection while sparing the nerve. OBJECTIVE: To demonstrate the use of SWIG in resection of cranial nerve schwannomas. METHODS: Three patients with cranial nerve schwannomas (i.e., trigeminal, vestibular, and vagus) underwent SWIG-guided resection. During surgery, NIR visualization was used intermittently used to detect fluorescence to guide resection. Signal-to-background ratio was then calculated to quantify fluorescence. RESULTS: Patients were infused with ICG at a dose of 5.0 mg/kg 24 hours before surgery. Each patient achieved total or near-total resection and relief of symptoms with lack of recurrence at six-month follow-up. The average SBR calculated was 3.79, comparable to values for SWIG-guided resection of other brain and spine tumors. CONCLUSION: This case series is the first published report of trigeminal and vagus nerve schwannoma resection using the SWIG technique and suggests that SWIG may be used to detect all schwannomas, alongside many other types of brain tumor. This paper also demonstrates the importance of preoperative ICG infusion timing and discusses the inverse pattern of NIR signal that may be observed when infusion occurs outside of the optimal timing. This provides direction for future studies investigating the administration of SWIG to resect cranial nerve schwannomas and other brain tumors.

Indocyanine green fluorescence applied to gynecologic oncology: beyond sentinel lymph node.

Indocyanine green (ICG), a well-known molecule employed in medicine for over five decades, has emerged as a versatile dye widely embraced across various surgical disciplines. In gynecologic oncology, its prevalent use revolves around the detection of sentinel lymph nodes. However, the true potential of ICG extends beyond this singular application, owing to its pragmatic utility, cost-effectiveness, and safety profile. Furthermore, ICG has been introduced in the theranostic landscape, marking a significant juncture in the evolution of its clinical utility. This narrative review aims to describe the expanding horizons of ICG fluorescence in gynecologic oncology, beyond the sentinel lymph node biopsy. The manifold applications reported within this manuscript include: 1) lymphography; 2) angiography; 3) nerve visualization; 4) ICG-driven resections; and 5) theranostic. The extensive exploration across these numerous applications, some of which are still in the preclinical phase, serves as a hypothesis generator, aiming to stimulate the development of clinical studies capable of expanding the use of this drug in our field, enhancing the care of gynecological cancer patients.

Comparative study using indocyanine green and patent blue dye for sentinel lymph node biopsy in patients with early-stage cervical cancer.

BACKGROUND: Lymphatic involvement is the most important prognostic factor in early-stage cervical cancer. Sentinel lymph node biopsy is a viable alternative to systematic lymphadenectomy and may identify metastases more precisely. OBJECTIVE: To compare two tracers (indocyanine green and patent blue) to detect sentinel nodes. METHODS: A single-center, retrospective study of women treated due to early-stage cervical cancer (International Federation of Gynecology and Obstetrics 2009 IA1 with lymphovascular invasion, IA2, and IB1). Location and tracer of all detected sentinel nodes had been documented for a prospective, multicenter trial (SENTIX trial). All sentinel nodes were sent to frozen section and final analysis through ultrastaging using a standard protocol. RESULTS: Overall, 103 patients were included. Bilateral detection rate for indocyanine green (93.2%) was significantly higher than for blue dye (77.7%; p=0.004). Their combined use significantly increased the bilateral detection to 99.0% (p=0.031). While 97.4% of all sentinel nodes were located below the common iliac vessels, no para-aortic nodes were labeled. Simultaneous bilateral detection with both tracers was found in 71.8% of the cases, of which the sentinel nodes were identical in 91.9%. Nine positive nodes were detected among seven patients (6.8%), all marked with indocyanine green while patent blue labeled six. Frozen section failed to detect one of three macrometastases and three of four micrometastases (sensitivity 43%; negative prediction value 96%). CONCLUSION: Anatomical distribution and topographic localization of the sentinel nodes obtained with these tracers were not different. Indocyanine green provided a significantly higher bilateral detection rate and had superior sensitivity to detect positive nodes compared with patent blue. Combining indocyanine green and blue dye increased the bilateral detection rate significantly.