To investigate whether the application of intravenous indocyanine green fluorescence imaging(ICG-FI) had advantage in intersegmental plane visualization and perioperative outcome than using traditional inflation-deflation method(control group) in thoracoscopic segmentectomy. We searched PubMed, Embase, Cochrane Library, EMBASE, Wanfang Database, VIP Database, and CNKI Database to include comparative studies focusing on the comparisons of ICG-FI and control, up to December 2022. We used standard mean differences (SMD, continuous variables) or risk ratios (RR, categorical variables) with their corresponding 95 % confidence interval (CI) were used to assess pooled effects. This analysis was conducted according to the PRISMA guideline. Total, seven published studies with 905 patients (ICG-FI group n = 428, control group n = 477) were included for further analysis. The ICG-FI group was significantly associated with less bleeding during the surgery (SMD = -0.23,95 % CI: -0.08∼-0.38, P < 0.05), shorter surgery time (SMD = -0.87, 95 % CI: -1.75∼-0.17, P < 0.05) and intersegmental boundary line (IBL) presentation time (SMD = -4.50, 95 % CI: -4.97∼-4.07, P < 0.01). The ICG-FI group had shorter postoperative hospitalization time (SMD = -0.18, 95 % CI: -0.34∼-0.03), P < 0.05), and the drainage duration (SMD = -0.18, 95 % CI: -0.34∼-0.03,P < 0.05) than that in the control group. The ICG-FI group also showed the less postoperative complications (RR = 0.75, 95 % CI: 0.64-0.88). There were no significant differences in the number of lymph node resection. No significant publication bias were found in this analysis. Compared with inflation-deflation method, application of ICG-FI in thoracoscopic segmentectomy could reduce operation time, IBL presentation time, length of hospital stay, intraoperative blood loss, and overall complication incidence.

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.
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.

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.

UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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 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.

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.

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.

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.
OBJECTIVE: 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.
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 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.

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