How to increase the success rate in microsurgical free and pedicled flap reconstructions with intraoperative multistep ICG imaging: A case series with 400 consecutive cases.

BACKGROUND: Over the last decade, microsurgical soft-tissue transfer became the gold standard for various reconstructions throughout the body. Continuous improvement of instruments and surgical techniques, such as intraoperative indocyanine green angiography (ICG-A), allowed for a very high success rate. This study aimed to assess and validate the role of a standard intraoperative ICG-A in free and pedicled flap surgery to improve overall outcomes. PATIENTS AND METHODS: From April 2018 to April 2023, 400 consecutive patients who underwent reconstruction using free and pedicled flaps were enrolled. ICG-A was always performed in a free flap after flap elevation, after microsurgical anastomosis, immediately after the flap inset, and after wound closure. In the pedicled flap, the sequential procedure was performed after flap elevation, flap inset, and wound closure. RESULTS: All 400 patients who underwent flap reconstruction using intraoperative ICG-A had an extremely low incidence of necrosis (0.75% partial necrosis among free and pedicled flaps) and reoperation for perfusion-related complications (0.75% due to acute ischemia and 0.50% due to flap congestion). Minor complications, such as hematoma, seroma, wound dehiscence, and wound infections, were managed with a second operation. No flaps were lost, and all patients were successfully treated. CONCLUSIONS: This study showed how systematic multistep ICG-A for intraoperative assessment of free and pedicled flap perfusion can significantly reduce the complication rate, including flap loss and re-exploration surgeries, in a time- and cost-effective manner.

Diagnostic laparoscopy with indocyanine green fluorescence test for the evaluation of intestinal perfusion in abdominal blunt injury: a case report.

BACKGROUND: The indocyanine green (ICG) fluorescence test has become a standard test in surgical procedures, facilitating the assessment of blood perfusion in real-time. While its utility in emergency surgeries for evaluating anastomotic blood supply is well-established, its application in trauma cases, especially those involving mesenteric hematoma, remains underexplored. Herein, we present a case to illustrate the efficacy of the ICG fluorescence test in such scenarios. CASE PRESENTATION: A 51-year-old man with uncontrolled hypertension suffered blunt abdominal trauma following a motor vehicle accident. We used the intra-operative ICG fluorescence test to chart the surgical plan for the patient. A combination of diagnostic laparoscopy with ICG fluorescence testing effectively excluded bowel ischemia, leading to the avoidance of intestinal resection and the need for a temporary ostomy. The patient resumed enteral nutrition. CONCLUSIONS: Our case underscores the efficacy of ICG fluorescence testing in assessing bowel viability and guiding surgical strategies in trauma patients with mesenteric hematoma. By facilitating real-time visualization of blood perfusion, ICG testing enables the adoption of conservative treatments in patients who would traditionally require more invasive surgical interventions, with minimal effect on operation time and cost.

Zwitterionic nanoparticles from indocyanine green dimerization for imaging-guided cancer phototherapy.

Indocyanine green (ICG), the only near-infrared (NIR) dye approved for clinical use, has received increasing attention as a theranostic agent wherein diagnosis (fluorescence) is combined with therapy (phototherapy), but suffers rapid hepatic clearance, poor photostability, and limited accumulation at tumor sites. Here we report that dimerized ICG can self-assemble to form zwitterionic nanoparticles (ZN-dICG), which generate fluorescence self-quenching but exhibit superior photothermal and photodynamic properties over ICG. The zwitterionic moieties confer ZN-dICG an ultralow critical micelle concentration and high colloidal stability with low non-specific binding in vivo. In addition, ZN-dICG can respond to the over-generated reactive oxygen species (ROSs) and dissociate to restore NIR fluorescence of ICG, amplifying the sensitivity via albumin binding for low-background imaging of tumors. Following systemic administration, ZN-dICG accumulated in tumors of xenograft-bearing mice for imaging primary and metastatic tumors, and induced tumor ablation under laser irradiation. The discovery of ZN-dICG would contribute to the design of translational phototheranostic platform with high biocompatibility. STATEMENT OF SIGNIFICANCE: Indocyanine green (ICG) has been extensively studied as a phototheranostic agent that combines imaging with phototherapies, but it suffers from rapid hepatic clearance, poor photostability, and limited accumulation at tumor sites. Here, we report a strategy to construct ICG dimers (ICG-tk-ICG) by conjugating two ICG molecules via a thioketal bond, which can self-assemble into zwitterionic nanoparticles (ZN-dICG) at ultralow critical micelle concentrations, exhibiting superior photothermal and photodynamic properties over ICG. ZN-dICG responds to the over-generated ROS in tumors and dissociates to restore the NIR fluorescence of ICG, enhancing the sensitivity via albumin binding for low-background imaging of tumors. This study offers a supramolecular strategy that may potentiate the clinical translation of ICG in imaging-guided cancer phototherapy.

"The Green Peace" How ICG can prevent complications in endometriosis surgery?

This literature review summarises the investigation into using Indocyanine Green (ICG) in the surgical management of endometriosis, focusing mainly on its application in Deep Endometriosis (DE). The study reviews the development, fluorescence characteristics, and clinical usage of ICG in enhancing the precision of identifying endometrial lesions during surgery. Emphasizing the technology's contribution to improved lesion visualisation, the paper discusses how ICG facilitates increased diagnostic accuracy, potentially reducing recurrence rates and the necessity for subsequent interventions. Additionally, it explores ICG's role in minimizing the risk of iatrogenic injuries, especially in ureteral endometriosis, and its utility in surgical decision-making for rectosigmoid endometriosis by evaluating bowel perfusion. Conclusively, while acknowledging the clear benefits of ICG integration in endometriosis surgical procedures, the abstract calls for more extensive research to validate its efficacy and cost-efficiency in the broader context of endometriosis treatment.

"Rigid-Flexible" Dual-Ferrocene Chimeric Nanonetwork for Simultaneous Tumor-Targeted Tracing and Photothermal/Photodynamic Therapy.

There is an urgent need to develop phototherapeutic agents with imaging capabilities to assess the treatment process and efficacy in real-time during cancer phototherapy for precision cancer therapy. The safe near-infrared (NIR) fluorescent dyes have garnered significant attention and are desirable for theranostics agents. However, until now, achieving excellent photostability and fluorescence (FL) imaging capability in aggregation-caused quenching (ACQ) dyes remains a big challenge. Here, for the only FDA-approved NIR dye, indocyanine green (ICG), we developed a dual-ferrocene (Fc) chimeric nanonetwork ICG@HFFC based on the rigid-flexible strategy through one-step self-assembly, which uses rigid Fc-modified hyaluronic acid (HA) copolymer (HA-Fc) and flexible octadecylamine (ODA) bonded Fc (Fc-C18) as the delivery system. HA-Fc reserved the ability of HA to target the CD44 receptor of the tumor cell surface, and the dual-Fc region provided a rigid space for securely binding ICG through metal-ligand interaction and π-π conjugation, ensuring excellent photostability. Additionally, the alkyl chain provided flexible confinement for the remaining ICG through hydrophobic forces, preserving its FL. Thereby, a balance is achieved between outstanding photostability and FL imaging capability. In vitro studies showed improved photobleaching resistance, enhanced FL stability, and increased singlet oxygen (1O2) production efficiency in ICG@HFFC. Further in vivo results display that ICG@HFFC had good tumor tracing ability and significant tumor inhibition which also exhibited good biocompatibility.. Therefore, ICG@HFFC provides an encouraging strategy to realize simultaneous enhanced tumor tracing and photothermal/photodynamic therapy (PTT/PDT) and offers a novel approach to address the limitations of ACQ dyes.

Feasibility and Diagnostic Accuracy of Ultrastaging in the Detection of Micrometastases in Sentinel and Non-sentinel Lymph Nodes in Cervical Cancer: A Single-Center Retrospective Study With a Five-Year Follow-Up Period.

BACKGROUND: Cervical cancer is the fourth most common cause of malignant tumor-related deaths among women in developing nations. Cervical cancer has been estimated to cause 527.600 new cases and 265.700 deaths globally per year. OBJECTIVES: This study aimed to evaluate patients with cervical cancer by ultrastaging all the lymph nodes (LN), sentinel LN (SLN) and non-SLN, to increase the sensitivity of the detection of LN metastases and the diagnostic accuracy in cervical cancer with a five-year follow-up. MATERIALS AND METHODS: This is a retrospective study of 14 cervical cancer cases from 2017 to 2019 at the Municipal Emergency Clinical Hospital of Timisoara, Romania. The cases were selected based on their high risk of LN involvement but negative intraoperative pathologic LN. After re-evaluating all paraffin block biopsy samples from 29 cases, 14 cases were included in the study, which met all criteria for ultrastaging on surgical biopsy samples. RESULTS: Patients' ages included in the study ranged from 43 to 70 years (median: 57.14 years). According to the International Federation of Gynecology and Obstetrics (FIGO) staging, the majority of the patients were in stage IB: seven cases (50%). The study revealed a positive correlation between patient age and FIGO staging, with Pearson's correlation coefficient of 0.707 and a p-value of less than 0.05, indicating that older patients were more likely to be diagnosed with a higher FIGO stage. The mean follow-up was 34.5 months, and the median follow-up was 36 months (range: 6-60 months). We obtained 167 nodes, with a mean of 11.92 nodes/case. Twenty-one LN were found to be positive with the ultrastaging method. We detected 11 LN with macrometastases (MAC) (52.38%), seven with micrometastasis (MIC) (33.3%), and three with tumor cell islets (14.4%). That would be 13% of newly diagnosed ultrastaging cases as positive nodes. This ultrastaging method detected nodal MIC in eight (57.1%) out of the 14 patients, who initially tested negative for LN involvement using the routine Hematoxylin and Eosin (HE) method. The detection of micrometastases in these patients underscored the superior sensitivity of ultrastaging, which was further highlighted by the subsequent relapse of four (28.57%) out of these eight patients. The study also found no correlation between the FIGO standardization and the number of MIC found in these patients. CONCLUSIONS: Predicting cervical LN metastasis (LNM) is crucial for improving survival rates and reducing recurrence. Very few small cohort studies used an ultrastaging method to assess non-SLNs; most of them only assessed SLNs. We showed in our study that the ultrastaging method, both in the case of SLN and non-SLN, is superior compared with H&E analysis, with a 13% rate of new positive nodule diagnosis. Metastatic involvement of non-SLN was found in over 50% of all cases (8/14) according to the ultrastaging method. Additionally, our study confirms that the sensitivity of SLN ultrastaging is high for the presence of both MIC and MAC in SLN pelvic LN. As a result, we feel that ultrastaging is the most effective method for SLN analysis in patients with early-stage cervical cancer, and bilateral detection is preferable, significantly reducing false-negative results. The routine use of SLN along with ultrastaging would lead to more accurate surgical staging and better oncological follow-up of cases.

The potential of indocyanine green fluorescence detection in surgical cut margin of breast conserving surgery.

Background: Fluorescence-guided surgery (FGS) is a cutting-edge technology that uses near-infrared (NIR) fluorescence imaging to guide surgeons in surgery. Indocyanine green (ICG) is a fluorescent dye, which can be used for in vivo imaging of tumor cells. We aimed to explore the use of ICG fluorescence-guided technology as a rapid intraoperative margin assessment method for breast cancer surgery. In addition, we also compared the dose selection of ICG. Methods: This was a non-randomized prospective cohort study. Data were collected between August 2021 and October 2022 in the Division of Breast Surgery, Department of General Surgery, Nanjing Drum Tower Hospital, the Affiliated Hospital of Medical School, Nanjing University. Upon specimen removal, tumor margins were immediately analyzed by ICG fluorescence detection and then sent to the pathology department for intraoperative frozen section analysis and subsequent routine pathological examination. Abnormal margin rates were calculated and compared using intraoperative frozen section analysis and under the guidance of ICG fluorescence. Results: The study included 69 cases of breast cancer patients who underwent tumor resection assisted by ICG fluorescence-guided technology, including 18 patients with a 0.5 mg/kg dose and 51 patients with a 1.0 mg/kg dose. According to the study findings, the ICG test achieved a sensitivity of 81.82% and a specificity of 75.82%. At a dose of 0.5 mg/kg, the sensitivity was 66.67% whereas the specificity was 93.33%. At the dose of 1 mg/kg, the sensitivity was 87.5%, and the specificity was 74.42%. Similarly, for intraoperative frozen section analysis, the sensitivity was 81.82%, but the specificity was enhanced to 94.83%. Positive surgical cut margin was not identified in 2/69 by ICG fluorescence and frozen section analysis respectively. Conclusions: The sensitivity of ICG fluorescence detection is comparable to that of frozen section analysis, but the specificity is poor. The sensitivity increased and the specificity decreased at 1 mg/kg compared to the 0.5 mg/kg dose. ICG fluorescence can be used as a supplementary tool for frozen section analysis. These findings support further development and clinical performance assessment of ICG fluorescence.

Indocyanine green J-aggregate (IJA) theranostics: Challenges and opportunities.

Indocyanine green is an FDA-approved fluorescent imaging dye used for determining cardiac output, hepatic function, liver blood flow, and retinal perfusion. It has been investigated preclinically in photoacoustic imaging and photothermal therapy (PTT); however, ICG photodegradation limits its biomedical applications. An aggregated form of ICG, known as J-aggregate (IJA), exhibits superior photoacoustic signals and thermal stability than the monomeric ICG. Nevertheless, IJA still suffers from low stability in the biological milieu, and short in vivo blood circulation. To address these limitations, a range of nanocarriers have been developed to enhance IJA stability and performance. This review focuses on IJA potentials and limitations, besides the recent development of IJA-loaded nanocarriers, particularly for cancer imaging and therapy.

Fluorescence and tracers in surgery: the coming future.

The revolution that we are seeing in the world of surgery will determine the way we understand surgical approaches in coming years. Since the implementation of minimally invasive surgery, innovations have constantly been developed to allow the laparoscopic approach to go further and be applied to more and more procedures. In recent years, we have been in the middle of another revolutionary era, with robotic surgery, the application of artificial intelligence and image-guided surgery. The latter includes 3D reconstructions for surgical planning, virtual reality, holograms or tracer-guided surgery, where ICG-guided fluorescence has provided a different perspective on surgery. ICG has been used to identify anatomical structures, assess tissue perfusion, and identify tumors or tumor lymphatic drainage. But the most important thing is that this technology has come hand in hand with the potential to develop other types of tracers that will facilitate the identification of tumor cells and ureters, as well as different light beams to identify anatomical structures. These will lead to other types of systems to assess tissue perfusion without the use of tracers, such as hyperspectral imaging. Combined with the upcoming introduction of ICG quantification, these developments represent a real revolution in the surgical world. With the imminent implementation of these technological advances, a review of their clinical application in general surgery is timely, and this review serves that aim.

Corrigendum: Comparison of indocyanine green angiography and swept-source wide-field optical coherence tomography angiography in posterior uveitis.

[This corrects the article DOI: 10.3389/fmed.2022.853315.].

Dose Optimization of Intravenous Indocyanine Green for Malignant Lung Tumor Localization.

Background: Intravenously administered indocyanine green (ICG) accumulates in lung tumors, facilitating their detection via a fluorescence spectrum measurement. This method aids in identifying tumor locations that are invisible to the naked eye. We aim to determine the optimal ICG dose and administration method for accurate tumor identification during lung resection surgeries, utilizing a novel ICG fluorescence spectroscopy system for precise tumor localization. Materials and Methods: ICG should be dissolved in the provided solution or distilled water and administered intravenously approximately 24 h before surgery, beginning with an initial dose of 0.5 mg/kg. If the tumor detection rate is insufficient, the dose may be gradually increased to a maximum of 5.0 mg/kg to determine the optimal dosage for effective tumor detection. This fluorescence spectroscopy during surgery may reveal additional lesions that remain undetected in preoperative assessments. The primary endpoint includes the correct diagnostic rate of tumor localization. The secondary endpoints include the measurement of the intraoperative ICG fluorescence spectral intensity in lung tumors, the assessment of the operability and safety of intraperitoneal ICG administrations, the measurement of the ICG fluorescence spectral intensity in surgical specimens, the comparison of the spectral intensity in lung tissues during collapse and expansion, the correlation between ICG camera images and fluorescence spectral intensity, and the comparison of fluorescence analysis results with histopathological findings. The trial has been registered in the jRCT Clinical Trials Registry under the code jRCTs011230037. Results and Conclusions: This trial aims to establish an effective methodology for localizing and diagnosing malignant lung tumors, thereby potentially improving surgical outcomes and refining treatment protocols.

Quantification of fluorescence angiography for visceral perfusion assessment: measuring agreement between two software algorithms.

BACKGROUND: Indocyanine green fluorescence angiography (ICG-FA) may reduce perfusion-related complications of gastrointestinal anastomosis. Software implementations for quantifying ICG-FA are emerging to overcome a subjective interpretation of the technology. Comparison between quantification algorithms is needed to judge its external validity. This study aimed to measure the agreement for visceral perfusion assessment between two independently developed quantification software implementations. METHODS: This retrospective cohort analysis included standardized ICG-FA video recordings of patients who underwent esophagectomy with gastric conduit reconstruction between August 2020 until February 2022. Recordings were analyzed by two quantification software implementations: AMS and CPH. The quantitative parameter used to measure visceral perfusion was the normalized maximum slope derived from fluorescence time curves. The agreement between AMS and CPH was evaluated in a Bland-Altman analysis. The relation between the intraoperative measurement of perfusion and the incidence of anastomotic leakage was determined for both software implementations. RESULTS: Seventy pre-anastomosis ICG-FA recordings were included in the study. The Bland-Altman analysis indicated a mean relative difference of + 58.2% in the measurement of the normalized maximum slope when comparing the AMS software to CPH. The agreement between AMS and CPH deteriorated as the magnitude of the measured values increased, revealing a proportional (linear) bias (R2 = 0.512, p < 0.001). Neither the AMS nor the CPH measurements of the normalized maximum slope held a significant relationship with the occurrence of anastomotic leakage (median of 0.081 versus 0.074, p = 0.32 and 0.041 vs 0.042, p = 0.51, respectively). CONCLUSION: This is the first study to demonstrate technical differences in software implementations that can lead to discrepancies in ICG-FA quantification in human clinical cases. The possible variation among software-based quantification methods should be considered when interpreting studies that report quantitative ICG-FA parameters and derived thresholds, as there may be a limited external validity.

Use of Indocyanine Green to Detect Intraoperative Staple-Line Leaks in Robotic Bariatric Surgery: An Observational Cohort Study.

Background Bariatric surgeries aid weight loss in patients with morbid obesity, yet staple-line leaks pose safety concerns. Multiple methods are used to help identify these links. Intraluminal indocyanine green (ICG) has been shown to be useful in other applications, and its use in robotic bariatric surgeries is underexplored. Objective The primary objective of this research project was to demonstrate the usage of intraluminal ICG in detecting staple-line leaks during robotic sleeve gastrectomy and robotic gastric bypass. Settings The research was conducted at Bronxcare Health System between June 2022 and June 2023. Methods We studied 150 consecutive participants undergoing robotic sleeve gastrectomy or robotic gastric bypass. Intraluminal ICG was used in each case in order to identify leaks. Data on comorbidities, detected intraoperative leaks, and detected postoperative leaks were collected. Results Out of the 150 patients who underwent robotic bariatric surgeries (139 for sleeve gastrectomy and 11 for gastric bypass), four cases (two for each procedure) were identified with intraoperative leaks using ICG, resulting in an overall 2.66% incidence rate. In those four patients with intraoperative leaks, reinforcing sutures and a drain were placed. Following the surgeries, none of the patients had radiologic or clinical leaks identified. Conclusions Intraluminal ICG presents a novel approach for detecting staple-line leaks in robotic bariatric surgery. Future studies can be done to look at a larger series of patients and compare leak detection rates between ICG and other methods.

The effect of hypotonic pharmacologic lipodissolution on abdominal free flap perfusion: a case report.

Background: Hypotonic pharmacologic lipodissolution (HPL) has gained popularity as a treatment for abdominal fat reduction, especially among Asian individuals. However, research on the effect of HPL on abdominal vascularity and abdominal autologous tissue flap are limited. Case Description: This case report describes a patient who underwent HPL treatment in November 2022 and subsequently underwent nipple-sparing mastectomy with free transverse rectus abdominis musculocutaneous (TRAM) flap reconstruction on April 4, 2023. The preoperative evaluation included computed tomography (CT) angiography to assess the viability of abdominal perforators and vasculature for TRAM flap reconstruction. Intraoperatively, indocyanine green (ICG) fluoroscopy was performed after TRAM flap elevation to evaluate flap perfusion. The findings revealed compromised skin-side perfusion but satisfactory deep layer perfusion, with subdermal plexus perfusion observed during de-epithelialization. Conclusions: These findings suggest that in nipple sparing mastectomy cases with minimal skin flap preservation requirements, a history of HPL may have less negative impact on TRAM flap reconstruction. However, in skin sparing mastectomy cases with extensive skin flap preservation needs, careful assessment, including preoperative CT angiography and intraoperative ICG imaging, is essential to minimize the risk of partial flap necrosis.

The use of intravenous indocyanine green in minimally invasive segmental lung resections: a systematic review.

Background: To identify intersegmental planes (ISPs) in video/robot-assisted thoracoscopic segmentectomies, indocyanine green (ICG) is commonly used. The aim of this systematic review is to evaluate the efficacy of intravenous ICG in the identification of ISP. Methods: A systematic search was performed. Studies evaluating patients who underwent a video/robot-assisted thoracoscopic segmentectomy using intravenous ICG were included. The primary outcome measure was the frequency and percentage of patients in whom the ISP was adequately visualized. Secondary outcomes encompassed the ICG dose, time to visualization, time to maximum ICG visualization, time to disappearance of ICG effect and adverse reactions to ICG. Results: Eighteen studies were included for systematic review, enrolling a total of 1,090 patients. Irrespective of the injected dose, intravenous ICG identified the ISP in 94% of the cases (range, 30-100%). Overall, there was a considerable amount of heterogeneity regarding the injected dose of ICG (range, 5-25 mg or 0.05-0.5 mg/kg). The mean time before first effect of ICG was visible ranged from 10 to 40 seconds. The mean total time of ICG visibility ranged from 90 to 140 seconds after a bolus injection and was 170 seconds after continuous infusion. No adverse reactions were reported. Conclusions: After administration of intravenous ICG, visualization of the ISP is successful in up to 94% of cases, even after administration of a low dose (0.05 mg/kg) of ICG. The use of intravenous ICG is safe with no reported adverse effects in the immediate peri-operative period.

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.

Biliary Anatomy Visualization and Surgeon Satisfaction Using Standard Cholangiography versus Indocyanine Green Fluorescent Cholangiography during Elective Laparoscopic Cholecystectomy: A Randomized Controlled Trial.

Background: Intraoperative biliary anatomy recognition is crucial for safety during laparoscopic cholecystectomy, since iatrogenic bile duct injuries represent a fatal complication, occurring in up to 0.9% of patients. Indocyanine green fluorescence cholangiography (ICG-FC) is a safe and cost-effective procedure for achieving a critical view of safety and recognizing early biliary injuries. The aim of this study is to compare the perioperative outcomes, usefulness and safety of standard intraoperative cholangiography (IOC) with ICG-FC with intravenous ICG. Methods: Between 1 June 2021 and 31 December 2022, 160 patients undergoing elective LC were randomized into two equal groups: Group A (standard IOC) and group B (ICG-FC with intravenous ICG). Results: No significant difference was found between the two groups regarding demographics, surgery indication or surgery duration. No significant difference was found regarding the visualization of critical biliary structures. However, the surgeon satisfaction and cholangiography duration presented significant differences in favor of ICG-FC. Regarding the inflammatory response, a significant difference between the two groups was found only in postoperative WBC levels. Hepatic and renal function test results were not significantly different between the two groups on the first postoperative day, except for direct bilirubin. No statistically significant difference was noted regarding 30-day postoperative complications, while none of the complications noted included bile duct injury events. Conclusions: ICG-FC presents equivalent results to IOC regarding extrahepatic biliary visualization and postoperative complications. However, more studies need to be performed in order to standardize the optimal dose, timing and mode of administration.

Indocyanine-Green-Loaded Liposomes for Photodynamic and Photothermal Therapies: Inducing Apoptosis and Ferroptosis in Cancer Cells with Implications beyond Oral Cancer.

Oral cancer represents a global health burden, necessitating novel therapeutic strategies. Photodynamic and photothermal therapies using indocyanine green (ICG) have shown promise due to their distinctive near-infrared (NIR) light absorption characteristics and FDA-approved safety profiles. This study develops ICG-loaded liposomes (Lipo-ICGs) to further explore their potential in oral cancer treatments. We synthesized and characterized the Lipo-ICGs, conducted in vitro cell culture experiments to assess cellular uptake and photodynamic/photothermal effects, and performed in vivo animal studies to evaluate their therapeutic efficacy. Quantitative cell apoptosis and gene expression variation were further characterized using flow cytometry and RNA sequencing, respectively. Lipo-ICGs demonstrated a uniform molecular weight distribution among particles. The in vitro studies showed a successful internalization of Lipo-ICGs into the cells and a significant photodynamic treatment effect. The in vivo studies confirmed the efficient delivery of Lipo-ICGs to tumor sites and successful tumor growth inhibition following photodynamic therapy. Moreover, light exposure induced a time-sensitive photothermal effect, facilitating the further release of ICG, and enhancing the treatment efficacy. RNA sequencing data showed significant changes in gene expression patterns upon Lipo-ICG treatment, suggesting the activation of apoptosis and ferroptosis pathways. The findings demonstrate the potential of Lipo-ICGs as a therapeutic tool for oral cancer management, potentially extending to other cancer types.

Safety and efficacy of indocyanine green fluorescence imaging for real-time guidance of laparoscopic thermal ablation in patients with liver cancer.

PURPOSE: To evaluate the safety and efficacy of indocyanine green fluorescence imaging for real-time guidance of laparoscopic thermal ablation in patients with liver cancer. MATERIALS AND METHODS: A total of 27 patients with 40 liver lesions underwent fluorescence-assisted laparoscopic ablation between January 2020 to March 2023. The sensitivity of indocyanine green (ICG)-fluorescence imaging, technique effectiveness rate and complications of fluorescence-assisted laparoscopic thermal ablation were evaluated. RESULTS: In total, 33 out of the 40 lesions were identified by ICG-fluorescence imaging technique, with the sensitivity of 82.5%. The sensitivity of ICG-fluorescence imaging of tumor detection in liver surface of parenchyma was significantly higher than that in the deeply located hepatic parenchyma (96.8% vs 33.3%, p = 0.002). ICG-fluorescence imaging procedures detected 4 lesions that cannot be seen on intraoperative ultrasound. It provides clear demarcation lines on the hepatic surface. Technical success is achieved if the necrotic zone had at least a 5 mm ablative margin around the outer edge of the ICG-fluorescence image. Technical success of fluorescence laparoscopic radiofrequency ablation (FLRFA) and fluorescence laparoscopic microwave ablation (FLMWA) was 100% (27/27). Technical effectiveness is defined by the complete necrotic lesions of the local tumor tissue during follow-up. According to the CT/MRI one month after FLRFA or FLMWA, the technical efficacy rate was 92.5% (37/40) and local tumor progression occurred in 7.5% (3/40) of the enrolled lesions. During the follow-up period, no major complications were observed. CONCLUSION: ICG-fluorescence imaging guided laparoscopic thermal ablation was feasible, safe and effective.

Utility of indocyanine green fluorescent dye in emergency general surgery: a review of the contemporary literature.

For decades, indocyanine green (ICG) has been available for medical and surgical use. The indications for ICG use in surgery have expanded where guided surgery directed by fluorescence and near-infrared fluorescent imaging offers numerous advantages. Recently, surgeons have reported using ICG operative navigation in the emergency setting, with fluorescent cholangiography being the most common procedure. The utility of ICG also involves real-time perfusion assessment, such as ischemic organs and limbs. The rising use of ICG in surgery can be explained by the ICG's rapid technological evolution, accuracy, ease of use, and great potential to guide precision surgical diagnosis and management. The review aims to summarize the current literature on the uses of ICG in emergency general surgery. It provides a comprehensive and practical summary of the use of ICG, including indication, route of administration, and dosages. To simplify the application of ICG, we subdivided its use into anatomical mapping and perfusion assessment. Anatomical mapping includes the biliary tree, ureters, and bowel. Perfusion assessment includes bowel, pancreas, skin and soft tissue, and gonads. This review provides a reference to emergency general surgeons to aid in implementing ICG in the emergency setting for more enhanced and safer patient care.