Evaluation of the tumor-targeting specific imaging and killing effect of a CEA-targeting nanoparticle in colorectal cancer.

INTRODUCTION: Colorectal cancer (CRC) is a prevalent digestive malignancy with significant global mortality and morbidity rates. Improving diagnostic capabilities for CRC and investigating novel therapeutic approaches are pressing clinical imperatives. Additionally, carcinoembryonic antigen (CEA) has emerged as a highly promising candidate for both colorectal tumor imaging and treatment. METHODS: A novel active CEA-targeting nanoparticle, CEA(Ab)-MSNs-ICG-Pt, was designed and synthesized, which served as a tumor-specific fluorescence agent to help in CRC near-infrared (NIR) fluorescence imaging. In cell studies, CEA(Ab)-MSNs-ICG-Pt exhibited specific targeting to RKO cells through specific antibody-antigen binding of CEA, resulting in distribution both within and around these cells. The tumor-targeting-specific imaging capabilities of the nanoparticle were determined through in vivo fluorescence imaging experiments. Furthermore, the efficacy of the nanoparticle in delivering chemotherapeutics and its killing effect were evaluated both in vitro and in vivo. RESULTS: The CEA(Ab)-MSNs-ICG-Pt nanoparticle, designed as a novel targeting agent for carcinoembryonic antigen (CEA), exhibited dual functionality as a targeting fluorescent agent. This CEA-targeting nanoparticle showed exceptional efficacy in eradicating CRC cells in comparison to individual treatment modalities. Furthermore, it exhibits exceptional biosafety and biocompatibility properties. CEA(Ab)-MSNs-ICG-Pt exhibits significant promise due to its ability to selectively target tumors through NIR fluorescence imaging and effectively eradicate CRC cells with minimal adverse effects in both laboratory and in vivo environments. CONCLUSION: The favorable characteristics of CEA(Ab)-MSNs-ICG-Pt offer opportunities for its application in chemotherapeutic interventions, tumor-specific NIR fluorescence imaging, and fluorescence-guided surgical procedures.

Fluorescence imaging for real-time detection of breast cancer tumors using IV injection of indocyanine green with non-conventional imaging: a systematic review of preclinical and clinical studies of perioperative imaging technologies.

BACKGROUND: This review summarizes the available data on the effectiveness of indocyanine green fluorescence imaging (ICG-FI) for real-time detection of breast cancer (BC) tumors with perioperative imaging technologies. METHODS: PubMed and Scopus databases were exhaustively searched for publications on the use of the real-time ICG-FI evaluation of BC tumors with non-conventional breast imaging technologies. RESULTS: Twenty-three studies were included in this review. ICG-FI has been used for BC tumor identification in 12 orthotopic animal tumor experiences, 4 studies on animal assessment, and for 7 human clinical applications. The BC tumor-to-background ratio (TBR) was 1.1-8.5 in orthotopic tumor models and 1.4-3.9 in animal experiences. The detection of primary human BC tumors varied from 40% to 100%. The mean TBR reported for human BC varied from 2.1 to 3.7. In two studies evaluating BC surgical margins, good sensitivity (93.3% and 100%) and specificity (60% and 96%) have been reported, with a negative predictive value of ICG-FI to predict margin involvement intraoperatively of 100% in one study. CONCLUSIONS: The use of ICG-FI as a guiding tool for the real-time identification of BC tumors and for the assessment of tumor boundaries is promising. There is great variability between the studies with regard to timing and dose. Further evidence is needed to assess whether ICG-guided BC surgery may be implemented as a standard of care.

Indocyanine green angiography guidance for vascular preservation in skin and nipple sparing mastectomy.

PURPOSE: The skin and/or nipple-sparing approach has become an oncologically sound and desirable choice for women choosing mastectomy. Indocyanine green (ICG) perfusion imaging has been shown to reduce ischemic complications in mastectomy skin flaps. Immediate reconstruction requires a well-vascularized skin flap capable of tolerating full expansion. Identification of the perforating subcutaneous vessels to the skin envelope may allow for better and more consistent blood vessel preservation and flap perfusion. METHODS: The authors conducted an institutional review board-approved prospective study with 41 patients to assess the feasibility of using ICG perfusion imaging to visualize, cutaneously map, and preserve the vessels that supply the skin flap and nipple-areolar complex. For each patient, the number of vessels initially mapped, the number of vessels preserved, the extent to which each vessel was preserved, and the proportion of the flap with adequate perfusion (as defined by the SPY-Q > 20% threshold) was recorded and analyzed. RESULTS: Vessels were able to be identified and marked in a high majority of patients (90%). There was a moderate linear relationship between the number of vessels marked and the number preserved. Successful mapping of vessels was associated with lower rates of wound breakdown (p = 0.036). Mapping and preserving at least one vessel led to excellent flap perfusion (> 90%). No increase in complications was observed from utilizing ICG angiography preoperatively. CONCLUSION: This prospective study using preoperative ICG perfusion mapping demonstrated safety, feasibility, and good prognostic outcomes. LEVEL OF EVIDENCE: III.

Breast lymphedema following breast-conserving treatment for breast cancer: current status and future directions.

PURPOSE: To examine the current evidence on breast lymphedema (BL) diagnosis and treatment after breast-conserving surgery, identify gaps in the literature, and propose future research directions. METHODS: A comprehensive literature review was conducted using Ovid, PubMed, and Cochrane, including studies published between 2000 and 2023. References were reviewed manually for eligible studies. Inclusion criteria were as follows: patients who underwent breast conserving treatment (surgery ± radiation) for breast cancer, goals of the paper included analyzing or reviewing BL measurement with ultrasound or tissue dielectric constant, or BL treatment. Twenty-seven manuscripts were included in the review. RESULTS: There is variation in incidence, time course, and risk factors for BL. Risk factors for BL included breast size, primary and axillary surgery extent, radiation, and chemotherapy but require further investigation. Diagnostic methods for BL currently rely on patient report and lack standardized criteria. Tissue dielectric constant (TDC) and ultrasound (US) emerged as promising ambulatory BL assessment tools; however, diagnostic thresholds and validation studies with ICG lymphography are needed to establish clinical utility. The evidence base for treatment of BL is weak, lacking high-quality studies. CONCLUSION: The natural history of BL is not well defined. TDC and US show promise as ambulatory assessment tools for BL; however, further validation with lymphatic imaging is required. BL treatment is not established in the literature. Longitudinal, prospective studies including pre-radiation measurements and validating with lymphatic imaging are required. These data will inform screening, diagnostic criteria, and evidence-based treatment parameters for patients with BL after breast-conserving surgery and radiation.

The Efficacy and Safety of an Indocyanine Green-Macroaggregated Albumin-Hyaluronic Acid Mixture (LuminoMark™) for Surgical Localization of Recurrent Thyroid Cancer.

BACKGROUND: The recurrence of thyroid cancer poses challenges compounded by postoperative fibrosis and anatomic changes. By overcoming the limitations of current localizing dye techniques, indocyanine green-macroaggregated albumin-hyaluronic acid (ICG-MAA-HA) mixture dye promises improved localization. This study aimed to evaluate the efficacy and safety of the dye for recurrent thyroid cancer. METHODS: The nine patients in this study underwent surgery and postoperative ultrasonography. The dye was injected into recurrent lesions in all the patients preoperatively. During surgery, the lesions were confirmed with an imaging system before and after excision. If the lesion was unidentifiable with the naked eye, surgical excision was performed under the corresponding fluorescent guide. Side effects related to the dye injection and completeness of the surgery were evaluated. RESULTS: No side effects such as bleeding, skin tattooing, or pain during or after the dye injection were reported, and no discoloration occurred that interfered with the surgical field of view during surgery. In three cases (33.3 %), because it was difficult to localize metastatic lesions with the naked eye, the operation was successfully completed using an imaging system. The completeness of the surgical resection was confirmed by ultrasonography after an average of 5 months postoperatively. CONCLUSION: The study found that ICG-MAA-HA dye effectively located metastatic and recurrent thyroid cancer and had favorable results in terms of minimal procedural side effects and potential for assisting the surgeon. A large-scale multi-institutional study is necessary to prove the clinical significance regarding patient survival and disease control.

Comparative Study of Indocyanine Green Fluorescence Imaging in Lung Cancer with Near-Infrared-I/II Windows.

BACKGROUND: We compare the application of intravenous indocyanine green (ICG) fluorescence imaging in lung cancer with near-infrared-I (NIR-I) and near-infrared-II (NIR-II) windows. METHODS: From March to December 2022, we enrolled patients who received an intravenous injection of ICG (5 mg/kg) 1 day before the planned lung cancer surgery. The lung cancer nodules were imaged by NIR-I/II fluorescence imaging systems, and the tumor-to-normal-tissue ratio (TNR) was calculated. In addition, the fluorescence intensity and signal-to-background ratio (SBR) of capillary glass tubes containing ICG covered with different thicknesses of lung tissue were measured by NIR-I/II fluorescence imaging systems. RESULTS: In this study, 102 patients were enrolled, and the mean age was 59.9 ± 9.2 years. A total of 96 (94.1%) and 98 (96.1%) lung nodules were successfully imaged with NIR-I and NIR-II fluorescence, and the TNR of NIR-II was significantly higher than that of NIR-I (3.9 ± 1.3 versus 2.4 ± 0.6, P < 0.001). In multiple linear regression, solid nodules (P < 0.001) and squamous cell carcinoma (P < 0.001) were independent predictors of a higher TNR of NIR-I/II. When capillary glass tubes were covered with lung tissue whose thickness was more than 2 mm, the fluorescence intensity and the SBR of NIR-II were significantly higher than those of NIR-I. CONCLUSIONS: We verified the feasibility of NIR-II fluorescence imaging in intravenous ICG lung cancer imaging for the first time. NIR-II fluorescence can improve the TNR and penetration depth of lung cancer with promising clinical prospects.

Video-Based Indocyanine Green Fluorescence Applied to Robotic Duodenum-Preserving Pancreatic Head Resection.

BACKGROUND: Duodenum-preserving pancreatic head resection (DPPHR) serves as a surgical intervention for managing benign and low-grade malignant neoplasms located in the head of the pancreas. This surgical approach enables the thorough excision of pancreatic head lesions, reducing the necessity for digestive tract reconstruction and enhancing the patient's quality of life.1 Performing a minimally invasive DPPHR is a complex surgical procedure, particularly when safeguarding the bile duct and the pancreaticoduodenal arterial arch. Robotic surgery is among the latest innovations in minimally invasive surgery and is widely used in many surgical specialties. It offers advantages such as rotatable surgical instruments, muscle tremor filters and up to 10-15 times three dimensional (3D) visual field,2 and achieves high flexibility and accuracy in surgical operations. Indocyanine green (ICG) fluorescence imaging technology is also applied to provide real-time intraoperative assessment of the biliary system and blood supply, which helps maintain the biliary system's integrity.3,4 We first report the complete procedure of ICG applied to the da Vinci robotic Xi system for preserving the DPPHR. METHODS: A 48-year-old female patient was diagnosed with pancreatic duct stones, chronic pancreatitis, and pancreatogenic diabetes. Enhanced computed tomography (CT) scans revealed pancreatic head stones, pancreatic atrophy, scattered calcifications, and a dilated pancreatic duct. An attempt at endoscopic retrograde cholangiopancreatography (ERCP) treatment was abandoned during hospitalization due to unsuccessful catheterization. Following informed consent from the patient and her family, a robotic DPPHR was conducted utilizing ICG fluorescence imaging technology. Approximately 60 min before the surgery, 2 mg of ICG was injected via the peripheral vein. The individual was positioned in a reclined posture with the upper part of the bed raised to an angle of 30° and a leftward tilt of 15°. Upon entering the abdominal cavity, existing adhesions were meticulously separated and the gastrocolic ligament was opened to expose the pancreas. The lower part of the pancreas was separated and the superior mesenteric vein (SMV) was identified at the inferior boundary of the pancreatic neck. The pancreas was cut upward and the pancreatic duct was severed using scissors. Dissection of the lateral wall of the portal vein-SMV in the pancreatic head segment was performed. Meticulous dissection was carried out along the pancreatic tissue, retracting the uncinate process of the pancreas in an upward and rightward direction. During the dissection, caution was exercised to protect the anterior and posterior pancreaticoduodenal arterial arch. By using ICG fluorescence imaging, the path of the common bile duct was identified and verified. Caution was exercised to avoid injuring the bile duct. After isolating the CBD, the head and uncinate process of the pancreas was entirely excised. Under the fluorescence imaging mode, the wholeness of the CBD was scrutinized for any potential seepage of the contrast agent. Ultimately, a Roux-en-Y end-to-side pancreaticojejunostomy (duct to mucosa) was executed. RESULTS: The surgery took 265 min and the estimated blood loss was about 150 mL. Without any postoperative complications, the patient was released from the hospital 13 days following the surgery. Postoperative pathology confirmed pancreatic duct stones and chronic pancreatitis. We have successfully performed four cases of robotic DPPHR using this technique, with only one patient experiencing a postoperative complication of pulmonary embolism. All patients were discharged successfully without any further complications. CONCLUSIONS: Employing ICG fluorescence imaging in a robotic DPPHR has been demonstrated to be both secure and achievable. This technique potentially provides novel therapeutic perspectives, particularly for patients with ambiguous delineation between pancreatic and biliary ductal structures.

Indocyanine Green Fluorescence-Guided Laparoscopic Anatomical Segmentectomy of Liver Segment 6: Surgical Strategy and Technical Details.

BACKGROUND: Because of the complex anatomy of the right posterior hepatic pedicle, there have been few reports on standardized laparoscopic portal territory staining-guided anatomical resection of liver segment 6 (LPTAR-S6). This study aimed to elucidate the indocyanine green (ICG) fluorescence staining methods for LPTAR-S6. PATIENTS AND METHODS: LPTAR-S6 can be performed using positive and negative fluorescence staining approaches. We implemented these two approaches for patients with hepatocellular carcinoma. Descriptions of the surgical strategy and technical details are presented. RESULTS: Two patients safely underwent LPTAR-S6 using a preoperative three-dimensional reconstruction plan. The intraoperative ICG fluorescence staining effect was satisfactory, and the anatomical landmarks were fully exposed. CONCLUSIONS: A detailed preoperative three-dimensional reconstruction plan, complete intraoperative application of real-time laparoscopic ultrasound guidance, and ICG fluorescence staining can result in accurate transection of the liver parenchyma during LPTAR-S6.

Intraoperative near infrared functional imaging of rectal cancer using artificial intelligence methods - now and near future state of the art.

Colorectal cancer remains a major cause of cancer death and morbidity worldwide. Surgery is a major treatment modality for primary and, increasingly, secondary curative therapy. However, with more patients being diagnosed with early stage and premalignant disease manifesting as large polyps, greater accuracy in diagnostic and therapeutic precision is needed right from the time of first endoscopic encounter. Rapid advancements in the field of artificial intelligence (AI), coupled with widespread availability of near infrared imaging (currently based around indocyanine green (ICG)) can enable colonoscopic tissue classification and prognostic stratification for significant polyps, in a similar manner to contemporary dynamic radiological perfusion imaging but with the advantage of being able to do so directly within interventional procedural time frames. It can provide an explainable method for immediate digital biopsies that could guide or even replace traditional forceps biopsies and provide guidance re margins (both areas where current practice is only approximately 80% accurate prior to definitive excision). Here, we discuss the concept and practice of AI enhanced ICG perfusion analysis for rectal cancer surgery while highlighting recent and essential near-future advancements. These include breakthrough developments in computer vision and time series analysis that allow for real-time quantification and classification of fluorescent perfusion signals of rectal cancer tissue intraoperatively that accurately distinguish between normal, benign, and malignant tissues in situ endoscopically, which are now undergoing international prospective validation (the Horizon Europe CLASSICA study). Next stage advancements may include detailed digital characterisation of small rectal malignancy based on intraoperative assessment of specific intratumoral fluorescent signal pattern. This could include T staging and intratumoral molecular process profiling (e.g. regarding angiogenesis, differentiation, inflammatory component, and tumour to stroma ratio) with the potential to accurately predict the microscopic local response to nonsurgical treatment enabling personalised therapy via decision support tools. Such advancements are also applicable to the next generation fluorophores and imaging agents currently emerging from clinical trials. In addition, by providing an understandable, applicable method for detailed tissue characterisation visually, such technology paves the way for acceptance of other AI methodology during surgery including, potentially, deep learning methods based on whole screen/video detailing.

A systematic methodology review of fluorescence-guided cancer surgery to inform the development of a core master protocol and outcome set.

BACKGROUND: Fluorescence-guided precision cancer surgery may improve survival and minimize patient morbidity. Efficient development of promising interventions is however hindered by a lack of common methodology. This methodology review aimed to synthesize descriptions of technique, governance processes, surgical learning and outcome reporting in studies of fluorescence-guided cancer surgery to provide guidance for the harmonized design of future studies. METHODS: A systematic search of MEDLINE, EMBASE and CENTRAL databases from 2016-2020 identified studies of all designs describing the use of fluorescence in cancer surgery. Dual screening and data extraction was conducted by two independent teams. RESULTS: Of 13,108 screened articles, 426 full text articles were included. The number of publications per year increased from 66 in 2016 to 115 in 2020. Indocyanine green was the most commonly used fluorescence agent (391, 91.8%). The most common reported purpose of fluorescence guided surgery was for lymph node mapping (195, 5%) and non-specific tumour visualization (94, 2%). Reporting about surgical learning and governance processes incomplete. A total of 2,577 verbatim outcomes were identified, with the commonly reported outcome lymph node detection (796, 30%). Measures of recurrence (32, 1.2%), change in operative plan (23, 0.9%), health economics (2, 0.1%), learning curve (2, 0.1%) and quality of life (2, 0.1%) were rarely reported. CONCLUSION: There was evidence of methodological heterogeneity that may hinder efficient evaluation of fluorescence surgery. Harmonization of the design of future studies may streamline innovation.

Coadministration of Quercetin and Indocyanine Green via PEGylated Phospholipid Micelles for Augmented Chem-Photothermal Combination Tumor Therapy.

A significant impediment persists in developing multicomponent nanomedicines designed to dismantle the heat shock protein (HSP)-based protective mechanism of malignant tumors during photothermal therapy. Herein, well-defined PEGylated phospholipid micelles were utilized to coencapsulate quercetin (QUE, a natural anticancer agent and potent HSP inhibitor) and indocyanine green (ICG, a photothermal agent) with the aim of achieving synchronized and synergistic drug effects. The subsequent investigations validated that the tailored micellar system effectively enhanced QUE's water solubility and augmented its cellular internalization efficiency. Intriguingly, the compositional PEGylated phospholipids induced extraordinary endoplasmic reticulum stress, thereby sensitizing the tumor cells to QUE. Furthermore, QUE played a crucial role in inhibiting the stress-induced overexpression of HSP70, thereby augmenting the photothermal efficacy of ICG. In systemic applications, the proposed nanotherapeutics exhibited preferential accumulation within tumors and exerted notable tumoricidal effects against 4T1 xenograft tumors under 808 nm near-infrared irradiation, facilitated by prominent near-infrared fluorescence imaging-guided chemo-photothermal therapy. Therefore, our strategy for fabricating multicomponent nanomedicines emerges as a coordinated platform for optimizing antitumor therapeutic efficacy and offers valuable insights for diverse therapeutic modalities.

Efficacy of indocyanine green fluorescence-guided inguinal lymph node dissection for penile cancer: a randomised trial.

OBJECTIVES: To investigate the safety and efficacy of indocyanine green (ICG) fluorescence-guided inguinal lymph node dissection (ILND) in patients with penile cancer. PATIENTS AND METHODS: A prospective, single-blind, randomised controlled clinical trial (ChiCTR2100044584) was performed among patients with penile caner who underwent bilateral modified ILND at four centres in China between 1 April 2021 and 30 June 2022. Patients aged 18-80 years and diagnosed with squamous cell carcinomas were included. Each enrolled patient was randomly assigned to either ICG fluorescence-guided ILND by a laparoscopic or robot-assisted approach in one groin, with non-ICG fluorescence-guided ILND in the other groin acting as a control. The primary outcome was the number of retrieved ILNs. Secondary outcomes included complications according to the Clavien-Dindo classification and the ILN non-compliance (inadequate removal of ILNs) rate. RESULTS: A total of 45 patients were included in the intention-to-treat (ITT) analysis, and the 42 who completed the entire study were included in the per protocol (PP) analysis. There were no ICG-related complications in any of the patients. The results of the ITT and PP analyses indicated that the total number of unilateral ILNs retrieved was higher on the ICG side than on the non-ICG side (mean 13 vs 9 ILNs, difference 4 ILNs [95% CI 2.7-4.4], P = 0.007), and the number of unilateral deep and superficial ILNs was higher on the ICG side. Furthermore, the LN non-compliance rate was lower on the ICG side than on the non-ICG side. Additionally, there was no significant difference in local complications in the groins between the two sides (P > 0.05). CONCLUSION: An ICG fluorescence-guided ILND was safe for patients with penile cancer. This procedure can improve the number of ILNs retrieved and reduce the LN non-compliance rate without increased complications. ICG fluorescence-guided ILND is beneficial and recommended for selected patients with penile cancer.

Near-infrared fluorescence-assisted superficial inguinal lymph-node excision for low-risk penile cancer.

OBJECTIVE: Identification of superficial inguinal lymph nodes during low-risk penile cancer surgery using near-infrared (NIR) fluorescence to improve the accuracy of lymph-node dissection and reduce the incidence of missed micrometastases and complications. METHODS: Thirty-two cases were selected, which were under the criteria of < T1, and no lymph-node metastasis was found with magnetic resonance imaging (MRI) detection. Two groups were randomly divided based on the fluorescence technique, the indocyanine green (ICG) group and the non-ICG group. In the ICG group, the ICG preparation was subcutaneously injected into the edge of the penile tumor 10 min before surgery, and the near-infrared fluorescence imager was used for observation. After the lymph nodes were visualized, the superficial inguinal lymph nodes were removed first, and then, the penis surgery was performed. The non-ICG group underwent superficial inguinal lymph-node dissection and penile surgery. RESULTS: Among the 16 patients in the ICG group, we obtained 11 lymph-node specimens using grayscale values of images (4.13 ± 0.72 vs. 3.00 ± 0.82 P = 0.003) along with shorter postoperative healing time (7.31 ± 1.08 vs. 8.88 ± 2.43 P = 0.025), and less lymphatic leakage (0 vs. 5 P = 0.04) than the 16 patients in the non-ICG group. Out of 11, 3 lymph nodes that are excised were further grouped into fluorescent and non-fluorescent regions (G1/G2) and found to be metastasized. CONCLUSION: Near-infrared fluorescence-assisted superficial inguinal lymph-node dissection in penile carcinoma is accurate and effective, and could reduce surgical complications.

Intraoperative indocyanine green angiography in preventing hypoparathyroidism after thyroid cancer surgery.

BACKGROUND: The aim of this study was to determine whether the use of indocyanine green angiography to identify devascularized parathyroids during thyroidectomy for thyroid cancer would decrease the rates of postoperative hypoparathyroidism. METHODS: Retrospective study of patients who had undergone total thyroidectomy for treatment of thyroid cancer between March 2021 and March 2023. The indocyanine group included patients with all four parathyroids identified and evaluated by indocyanine green angiography at the end of the procedure. Those with parathyroid glands classified with no vascularization had the glands autotransplanted. A group without indocyanine angiography was used to compare results. RESULTS: The analysis included 100 patients in each group. Indocyanine angiography identified 14.75% of devascularized parathyroids at surgery. The number of parathyroids with a score of 2 (i.e., good vascularization) was not a safe predictor of normal parathyroid hormone levels after surgery. Indeed, 29.2% of the patients with three parathyroids with a score of 2 developed transient hypoparathyroidism. Permanent hypoparathyroidism occurred in 7% of the patients without indocyanine group and in none of the patients in the indocyanine group (p = 0.014). CONCLUSION: Intraoperative angiography with indocyanine green could contribute to reduce the occurrence of permanent hypoparathyroidism in patients undergoing surgical treatment for thyroid cancer.

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.

In Vivo Dynamic and Static Analysis of Lymphatic Dysfunction in Lymphedema Using Near-Infrared Fluorescence Indocyanine Green Lymphangiography.

BACKGROUND: Near-infrared fluorescence indocyanine green lymphangiography, a primary modality for detecting lymphedema, which is a disease due to lymphatic obstruction, enables real-time observations of lymphatics and reveals not only the spatial distribution of drainage (static analysis) but also information on the lymphatic contraction (dynamic analysis). METHODS: We have produced total lymphatic obstruction in the upper limbs of 18 Sprague-Dawley rats through the dissection of proximal (brachial and axillary) lymph nodes and 20-Gy radiation (dissection limbs). After the model formation for 1 week, 9 animal models were observed for 6 weeks using near-infrared fluorescence indocyanine green lymphangiography by injecting 6-µL ICG-BSA (indocyanine green-bovine serum albumin) solution of 20-µg/mL concentration. The drainage pattern and leakage of lymph fluid were evaluated and time-domain signals of lymphatic contraction were observed in the distal lymphatic vessels. The obtained signals were converted to frequency-domain spectrums using signal processing. RESULTS: The results of both static and dynamic analyses proved to be effective in accurately identifying the extent of lymphatic disruption in the dissection limbs. The static analysis showed abnormal drainage patterns and increased leakage of lymph fluid to the periphery of the vessels compared with the control (normal) limbs. Meanwhile, the waveforms were changed and the contractile signal frequency increased by 58% in the dynamic analysis. Specifically, our findings revealed that regular lymphatic contractions, observed at a frequency range of 0.08 to 0.13 Hz in the control limbs, were absent in the dissection limbs. The contractile regularity was not fully restored for the follow-up period, indicating a persistent lymphatic obstruction. CONCLUSIONS: The dynamic analysis could detect the abnormalities of lymphatic circulation by observing the characteristics of signals, and it provided additional evaluation indicators that cannot be provided by the static analysis. Our findings may be useful for the early detection of the circulation problem as a functional evaluation indicator of the lymphatic system.

Investigation of the substituent effect of indocyanine green derivatives for lymph imaging.

Fluorescence lymph imaging with indocyanine green (ICG) is widely utilized as diagnostic tool for lymphatic diseases. While this technique offers numerous advantages, the kinetics of ICG at the injection site can pose challenges for a detailed diagnosis. In this study, we synthesized various ICG derivatives possessing cationic, anionic, or uncharged substituents and examined their photochemical properties, binding affinity to human serum albumin, as well as their correlation to pharmacokinetics in mice. The introduction of different substituents not only affected certain physiochemical properties, but also impacted the pharmacokinetics within the lymph nodes. Immunofluorescence imaging suggested that the extent of uptake of the ICG derivatives by phagocytic cells may affect the retention of the contrast ratios in the lymph nodes. These findings can provide new insights in the pharmacokinetics in lymphatic tissues, which could be useful for the development of novel fluorescent agents for lymph imaging.

Genetic alteration of SLCO1B3 defines constitutional indocyanine green excretory defect in patients who underwent hepatectomy.

AIM: Constitutional indocyanine green (ICG) excretory defects must be distinguished when assessing liver function. The absence of OATP1B3 expression due to homogenous alterations in the SLCO1B3 gene has been recently reported to induce ICG excretory defects; however, its association with the clinical examinations and the clinical implications of heterogeneous SLCO1B3 gene alteration remain unclear. METHODS: OATP1B3 expression was evaluated in 49 patients who underwent hepatectomy after evaluation of the ICG retention rate at 15 min (ICGR15) and technetium-99 m-galactosyl serum albumin (99mTc-GSA) hepatic scintigraphy. Additionally, alterations in SLCO1B3 were analyzed in patients without OATP1B3 expression. Subsequently, 59 patients who underwent hepatectomy for colorectal liver metastasis (CRLM) were analyzed. RESULTS: Of 49 patients, 6 (12%) had absent OATP1B3 expression. They had significantly higher ICGR15 value (74.7% vs. 23.5%; p < 0.0001), better modified albumin-bilirubin (ALBI) grade (≤grade 2A, 100% vs. 42%; p = 0.010), more normal 99mTc-GSA hepatic scintigraphy (100% vs. 28%; p = 0.0003), and better pathological liver fibrosis (F0-1, 100% vs. 49%; p = 0.027) compared to those with OATP1B3 expression. Three available frozen blocks of cases without OATP1B3 expression showed homozygous alterations in SLCO1B3. Of 59 patients with CRLM in normal liver background, five (8.5%) had heterozygous insertion in SLCO1B3, however they had no difference in ICGR15 values or other clinical findings compared to the other patients. CONCLUSIONS: Constitutional ICG excretory defects may be defined by the complete absence of OATP1B3 expression. The modified ALBI grade and 99mTc-GSA hepatic scintigraphy were useful for detecting constitutional ICG excretory defects.

Indocyanine green fluorescence angiography could reduce the risk of anastomotic leakage in rectal cancer surgery: a systematic review and meta-analysis of randomized controlled trials.

AIM: Several papers have shown that use of indocyanine green (ICG) decreases incidence of anastomotic leakage (AL) during colonic surgery, but no clear evidence has been found for rectal cancer surgery. Therefore, with this systematic review and meta-analysis of randomized controlled trials (RCTs) we aimed to assess if ICG could also reduce risk of AL in rectal cancer surgery. METHOD: PubMed, Scopus, CINAHL and Cochrane databases were searched for RCTs assessing the effect of intraoperative ICG on the incidence of AL of the colorectal anastomosis. Pooled relative risk (RR) and pooled risk difference (RD) were obtained using models with random effects. Risk of bias was evaluated with the Rob2 tool and the quality of evidence was assessed using the GRADE Pro tool. RESULTS: Four RCTs were included for analysis, with a total of 1510 patients (743 controls and 767 ICG patients). The rate of AL was 9% in the ICG group (69/767) and 13.9% (103/743) in the control group (p = 0.003, RR -0.5, 95% CI -0.827 to -0.172, heterogeneity test 0%, p = 0.460). The RD in terms of incidence of AL was significantly decreased by 4.51% (p = 0.031, 95% CI -0.086 to -0.004, heterogeneity test 28%, p = 0.182) when using ICG. CONCLUSION: Our meta-analysis suggested that use of ICG during rectal cancer surgery could reduce the rate of AL.

Clinical and computational development of a patient-calibrated ICGFA bowel transection recommender.

INTRODUCTION: Intraoperative indocyanine green fluorescence angiography (ICGFA) aims to reduce colorectal anastomotic complications. However, signal interpretation is inconsistent and confounded by patient physiology and system behaviours. Here, we demonstrate a proof of concept of a novel clinical and computational method for patient calibrated quantitative ICGFA (QICGFA) bowel transection recommendation. METHODS: Patients undergoing elective colorectal resection had colonic ICGFA both immediately after operative commencement prior to any dissection and again, as usual, just before anastomotic construction. Video recordings of both ICGFA acquisitions were blindly quantified post hoc across selected colonic regions of interest (ROIs) using tracking-quantification software and computationally compared with satisfactory perfusion assumed in second time-point ROIs, demonstrating 85% agreement with baseline ICGFA. ROI quantification outputs detailing projected perfusion sufficiency-insufficiency zones were compared to the actual surgeon-selected transection/anastomotic construction site for left/right-sided resections, respectively. Anastomotic outcomes were recorded, and tissue lactate was also measured in the devascularised colonic segment in a subgroup of patients. The novel perfusion zone projections were developed as full-screen recommendations via overlay heatmaps. RESULTS: No patient suffered intra- or early postoperative anastomotic complications. Following computational development (n = 14) the software recommended zone (ROI) contained the expert surgical site of transection in almost all cases (Jaccard similarity index 0.91) of the nine patient validation series. Previously published ICGFA time-series milestone descriptors correlated moderately well, but lactate measurements did not. High resolution augmented reality heatmaps presenting recommendations from all pixels of the bowel ICGFA were generated for all cases. CONCLUSIONS: By benchmarking to the patient's own baseline perfusion, this novel QICGFA method could allow the deployment of algorithmic personalised NIR bowel transection point recommendation in a way fitting existing clinical workflow.