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Background Early detection and treatment are effective methods for the management of oral squamous cell carcinoma (OSCC), which can be facilitated by the detection of tumor-specific OSCC biomarkers. The epidermal growth factor receptor (EGFR) and programmed death-ligand 1 (PD-L1) are important therapeutic targets for OSCC. Multispectral fluorescence molecular imaging (FMI) can facilitate the detection of tumor multitarget expression with high sensitivity and safety. Hence, we developed Nimotuzumab-ICG and Atezolizumab-Cy5.5 imaging probes, in combination with multispectral FMI, to sensitively and noninvasively identify EGFR and PD-L1 expression for the detection and comprehensive treatment of OSCC. Methods The expression of EGFR and PD-L1 was analyzed using bioinformatics data sources and specimens. Nimotuzumab-ICG and Atezolizumab-Cy5.5 imaging probes were developed and tested on preclinical OSCC cell line and orthotopic OSCC mouse model, fresh OSCC patients’ biopsied samples, and further clinical mouthwash trials were conducted in OSCC patients. Results EGFR and PD-L1 were specifically expressed in human OSCC cell lines and tumor xenografts. Nimotuzumab-ICG and Atezolizumab-Cy5.5 imaging probes can specifically target to the tumor sites in an in situ human OSCC mouse model with good safety. The detection sensitivity and specificity of Nimotuzumab-ICG in patients were 96.4% and 100%, and 95.2% and 88.9% for Atezolizumab-Cy5.5. Conclusions EGFR and PD-L1 are highly expressed in OSCC, the combination of which is important for a precise prognosis of OSCC. EGFR and PD-L1 expression can be sensitively detected using the newly synthesized multispectral fluorescence imaging probes Nimotuzumab-ICG and Atezolizumab-Cy5.5, which can facilitate the sensitive and specific detection of OSCC and improve treatment outcomes. Trial registration Chinese Clinical Trial Registry, ChiCTR2100045738. Registered 23 April 2021, https://www.chictr.org.cn/bin/project/edit?pid=125220

Background Early detection and treatment are critical for improving the survival and prognosis of patients with cervical cancer. However, there is a notable scarcity of targeted imaging probes specifically designed to detect high-grade squamous intraepithelial lesions (HSIL) and cervical cancer. Our study aimed to address this gap by identifying and validating a targeted imaging probe for these conditions. Results Using bioinformatics data, we identified galectin-7 (GAL7) as highly expressed in patients with cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC). Immunohistochemical staining of biopsy samples from 30 HSIL and cervical cancer patients verified the high and specific expression of GAL7. Further validation was performed using mouse and human CESC cell lines and tumor xenografts, confirming the consistent expression of GAL7. Based on this finding, we synthesized a GAL7-specific antibody conjugated with FITC, creating the GAL7-FITC fluorescence imaging probe. Fluorescence molecular imaging revealed that GAL7-FITC exhibited specific binding to various CESC cell lines and xenograft mouse models. Additionally, the diagnostic capability of GAL7-FITC was demonstrated in fresh HSIL specimens from cervical cone excisions, validated through histopathology and immunohistochemical analysis. Conclusions Our study identified GAL7 as a specific target for CESC and successfully developed the GAL7-FITC fluorescence imaging probe. GAL7-FITC has shown promising potential for clinical application in the early detection of HSIL and CESC, providing rapid fluorescence imaging diagnosis without observable toxicity. This advancement may significantly enhance the accuracy and speed of cervical cancer diagnostics, ultimately improving patient outcomes.

Background This study aimed to investigate the feasibility and clinical benefits of indocyanine green (ICG) inhalation for detecting air leak sites during video-assisted thoracoscopic surgery (VATS). Methods Between February 2023 and May 2023, a total of 288 patients underwent VATS were enrolled in this study. Among the population, 72 patients received ICG inhalation test following the traditional submersion sealing test. And 216 patients only underwent the submersion sealing test were matched using 1:3 propensity score matching analysis. The results of ICG inhalation test and the clinical outcomes were compared. Results In the ICG group, 48 air leak sites were detected in 25 patients (25/72, 34.7%). The conventional submersion sealing test identified 30 air leak sites, while the ICG inhalation test detected 47 sites. Among these detected air leak sites, 34 sites were repaired by suturing or stapling. The postoperative air leak rate in the ICG group (20.8%) was significantly lower than the control group (37.0%, P = 0.011). ICG inhalation test was a favorable factor for reducing postoperative air leaks (OR: 0.40; 95%CI: 0.20–0.78; P = 0.008). Conclusions The ICG inhalation test facilitates the identification of air leak sites that may have been overlooked in the conventional submersion sealing test. This technique is useful to reduce postoperative air leaks for patients undergoing VATS. Trial registration Chinese Clinical Trial Registry: ChiCTR2300067603 on January 13rd 2023.

Fluorescence endoscopy technology utilizes a light source of a specific wavelength to excite the fluorescence signals of biological tissues. This capability is extremely valuable for the early detection and precise diagnosis of pathological changes. Identifying a suitable experimental approach and metric for objectively and quantitatively assessing the imaging quality of fluorescence endoscopy is imperative to enhance the image evaluation criteria of fluorescence imaging technology. In this study, we propose a new set of standards for fluorescence endoscopy technology to evaluate the optical performance and image quality of fluorescence imaging objectively and quantitatively. This comprehensive set of standards encompasses fluorescence test models and imaging quality assessment protocols to ensure that the performance of fluorescence endoscopy systems meets the required standards. In addition, it aims to enhance the accuracy and uniformity of the results by standardizing testing procedures. The formulation of pivotal metrics and testing methodologies is anticipated to facilitate direct quantitative comparisons of the performance of fluorescence endoscopy devices. This advancement is expected to foster the harmonization of clinical and preclinical evaluations using fluorescence endoscopy imaging systems, thereby improving diagnostic precision and efficiency.

Supra‐maximum surgical tumor resection without neurological damage is highly valuable for treatment and prognosis of patients with glioblastoma multiforme (GBM). We developed a GBM‐specific fluorescence probe using IRDye800CW (peak absorption/emission, 778/795 nm) and bombesin (BBN), which (IRDye800‐BBN) targets the gastrin‐releasing peptide receptor, and evaluated the image‐guided resection efficiency, sensitivity, specificity, and survivability. Twenty‐nine patients with newly diagnosed GBM were enrolled. Sixteen hours preoperatively, IRDye800‐BBN (1 mg in 20 ml sterile water) was intravenously administered. A customized fluorescence surgical navigation system was used intraoperatively. Postoperatively, enhanced magnetic resonance images were used to assess the residual tumor volume, calculate the resection extent, and confirm whether complete resection was achieved. Tumor tissues and nonfluorescent brain tissue in adjacent noneloquent boundary areas were harvested and assessed for diagnostic accuracy. Complete resection was achieved in 82.76% of patients. The median extent of resection was 100% (range, 90.6–100%). Eighty‐nine samples were harvested, including 70 fluorescence‐positive and 19 fluorescence‐negative samples. The sensitivity and specificity of IRDye800‐BBN were 94.44% (95% CI, 85.65–98.21%) and 88.24% (95% CI, 62.25–97.94%), respectively. Twenty‐five patients were followed up (median, 13.5 [3.1–36.0] months), and 14 had died. The mean preoperative and immediate and 6‐month postoperative Karnofsky performance scores were 77.9 ± 11.8, 71.3 ± 19.2, and 82.6 ± 14.7, respectively. The median overall and progression‐free survival were 23.1 and 14.1 months, respectively. In conclusion, GBM‐specific fluorescent IRDye800‐BBN can help neurosurgeons identify the tumor boundary with sensitivity and specificity, and may improve survival outcomes.

Purpose China has the largest cancer population globally. Surgery is the main choice for most solid cancer patients. Intraoperative fluorescence molecular imaging (FMI) has shown its great potential in assisting surgeons in achieving precise resection. We summarized the typical applications of intraoperative FMI and several new trends to promote the development of precision surgery. Methods The academic database and NIH clinical trial platform were systematically evaluated. We focused on the clinical application of intraoperative FMI in China. Special emphasis was placed on a series of typical studies with new technologies or high-level evidence. The emerging strategy of combining FMI with other modalities was also discussed. Results The clinical applications of clinically approved indocyanine green (ICG), methylene blue (MB), or fluorescein are on the rise in different surgical departments. Intraoperative FMI has achieved precise lesion detection, sentinel lymph node mapping, and lymphangiography for many cancers. Nerve imaging is also exploring to reduce iatrogenic injuries. Through different administration routes, these fluorescent imaging agents provided encouraging results in surgical navigation. Meanwhile, designing new cancer-specific fluorescent tracers is expected to be a promising trend to further improve the surgical outcome. Conclusions Intraoperative FMI is in a rapid development in China. In-depth understanding of cancer-related molecular mechanisms is necessary to achieve precision surgery. Molecular-targeted fluorescent agents and multi-modal imaging techniques might play crucial roles in the era of precision surgery.

Novel strategies utilizing light in the second near-infrared region (NIR-II; 900–1,880 nm wavelengths) offer the potential to visualize and treat solid tumours with enhanced precision. Over the past few decades, numerous techniques leveraging NIR-II light have been developed with the aim of precisely eliminating tumours while maximally preserving organ function. During cancer surgery, NIR-II optical imaging enables the visualization of clinically occult lesions and surrounding vital structures with increased sensitivity and resolution, thereby enhancing surgical quality and improving patient prognosis. Furthermore, the use of NIR-II light promises to improve cancer phototherapy by enabling the selective delivery of increased therapeutic energy to tissues at greater depths. Initial clinical studies of NIR-II-based imaging and phototherapy have indicated impressive potential to decrease cancer recurrence, reduce complications and prolong survival. Despite the encouraging results achieved, clinical translation of innovative NIR-II techniques remains challenging and inefficient; multidisciplinary cooperation is necessary to bridge the gap between preclinical research and clinical practice, and thus accelerate the translation of technical advances into clinical benefits. In this Review, we summarize the available clinical data on NIR-II-based imaging and phototherapy, demonstrating the feasibility and utility of integrating these technologies into the treatment of cancer. We also introduce emerging NIR-II-based approaches with substantial potential to further enhance patient outcomes, while also highlighting the challenges associated with imminent clinical studies of these modalities.Expansion of the utilizable spectrum of light from the visible region to the near-infrared (NIR) window has greatly facilitated the clinical application of optical technologies for cancer imaging and phototherapy. However, use of light in the first NIR region (NIR-I) has important limitations, some of which might be overcome with emerging technologies utilizing NIR-II light. In this Review, the authors describe the current clinical experience with NIR-II-based cancer imaging and phototherapy, and discuss emerging NIR-II-based approaches that might further enhance patient outcomes. They also highlight challenges that will need to be addressed to translate NIR-II-based modalities from bench to bedside.

Intraoperative fluorescent imaging can provide real-time identification of tumours, lymph nodes, nerves and other healthy and malignant tissues during oncological surgery, contributing to better surgical outcomes. Various fluorescent probes have been clinically approved for surgical applications, improving tumour resection precision and preventing iatrogenic injury. In this Review, we discuss the development and application of fluorescent probes for image-guided surgery, including systemically and locally applied probes that are either non-targeted or targeted to specific tumours and tissues. We discuss the optimization and clinical potential of these probes, and highlight their current and future applications in oncological surgery. In addition, we examine the hardware of fluorescence imaging equipment, and discuss how artificial intelligence can enable real-time quantification to guide surgical decision-making. Finally, we highlight the remaining challenges in the field of image-guided surgery, including the need for standardization to achieve regulatory approval of new probes, and the required team effort for new probe development.Fluorescence imaging-guided surgery enables tumour resection with high precision, while preventing injury of healthy tissues. This Review discusses the clinical application and preclinical development of intraoperative fluorescence imaging probes and imaging equipment, including artificial intelligence algorithms.

Purpose Radical hysterectomy combined with pelvic lymphadenectomy is the standard treatment for early-stage cervical cancer, but unrecognized pelvic nerves are vulnerable to irreversible damage during surgery. This early clinical trial investigated the feasibility and safety of intraoperative near-infrared (NIR) fluorescence imaging (NIR-FI) with indocyanine green (ICG) for identifying pelvic nerves during radical hysterectomy for cervical cancer. Methods Sixty-six adults with cervical cancer were enrolled in this prospective, open-label, single-arm, single-center clinical trial. NIR-FI was performed in vivo to identify genitofemoral (GN), obturator (ON), and hypogastric (HN) nerves intraoperatively. The primary endpoint was the presence of fluorescence in pelvic nerves. Secondary endpoints were the ICG distribution in a nerve specimen and potential underlying causes of fluorescence emission in pelvic nerves. Results In total, 63 patients were analyzed. The ON was visualized bilaterally in 100% (63/63) of patients, with a mean fluorescence signal-to-background ratio (SBR) of 5.3±2.1. The GN was identified bilaterally in 93.7% (59/63) of patients and unilaterally in the remaining 4 patients, with a mean SBR of 4.1±1.9. The HN was identified bilaterally in 81.0% (51/63) of patients and unilaterally in 7.9% (5/63) of patients, with a mean SBR of 3.5±1.3. ICG fluorescence was detected in frozen sections of a nerve specimen, and was mainly distributed in axons. No ICG-related complications were observed. Conclusion This early clinical trial demonstrated the feasibility and safety of NIR-FI to visualize pelvic nerves intraoperatively. Thus, NIR-FI may help surgeons adjust surgical decision-making, avoid nerve damage, and improve surgical outcomes. Trial registration ClinicalTrials.gov NCT04224467

BackgroundThe role of intraoperative near-infrared fluorescence angiography with indocyanine green in reducing anastomotic leakage (AL) has been demonstrated in colorectal surgery, however, its perfusion assessment mode, and efficacy in reducing anastomotic leakage after laparoscopic intersphincteric resection (LsISR) need to be further elucidated.AimAim was to study near-infrared fluorescent angiography to help identify bowel ischemia to reduce AL after LsISR.Material and methodsA retrospective case-matched study was conducted in one referral center. A total of 556 consecutive patients with ultra-low rectal cancer including 140 patients with fluorescence angiography of epiploic appendages (FAEA)were enrolled. Perfusion assessment by FAEA in the monochrome fluorescence mode. Patients were divided into two groups based on perfusion assessment by FAEA. The primary endpoint was the AL rate within 6 months, and the secondary endpoint was the structural sequelae of anastomotic leakage (SSAL).ResultsAfter matching, the study group (n = 109) and control group (n = 190) were well-balanced. The AL rate in the FAEA group was lower before (3.6% vs. 10.1%, P = 0.026) and after matching (3.7% vs. 10.5%, P = 0.036). Propensity scores matching analysis (OR 0.275, 95% CI 0.035–0.937, P 0.039), inverse probability of treatment weighting (OR 0.814, 95% CI 0.765–0.921, P 0.002), and regression analysis (OR 0.298, 95% CI 0.112–0.790, P = 0.015), showed that FAEA was an independent protector factor for AL. This technique can significantly shorten postoperative hospital stay [9 (6–13) vs. 10 (8–13), P = 0.024] and reduce the risk of SSAL (1.4% vs. 6.0%, P = 0.029).ConclusionsPerfusion assessment by FAEA can achieve better visualization in LsISR and reduce the incidence of AL, subsequently avoiding SSAL after LsISR.