Owing to the high spatiotemporal resolution,the second near-infrared(NIR-II)imaging window can provide high imaging contrast with diminished tissue autofluorescence and suppressed photon scattering to pinpoint the loc...Owing to the high spatiotemporal resolution,the second near-infrared(NIR-II)imaging window can provide high imaging contrast with diminished tissue autofluorescence and suppressed photon scattering to pinpoint the locations for tumor surgery.Due to the unique optical properties and excellent fluorescence performance,quantum dots(QDs)are regarded as ideal nanoprobes for fluorescence-guided surgery(FGS).Moreover,QDs can be excited by a variety of light sources owing to the continuous and wide absorption ranges.Herein,light-emitting diode(LED)was used as the excitation source of QDs-based nanoprobes to realize FGS of tumor with high resolution.Since the LED light could irradiate a large region with consistent light intensity,signal distortion at the edge of imaging field was avoided.The signal intensity of the view edges under LED excitation can be improved by about 5 times compared to laser excitation.Therefore,more micro-vessels and smaller tumors(Vtumor<5 mm^(2))could be detected,thus providing more precise guidance for tumor resection surgery.展开更多
Fluorescence navigation is a novel technique for accurately identifying hepatocellular carcinoma(HCC)lesions during hepatectomy,enabling real-time visualization.Indocyanine green-based fluorescence guidance has been c...Fluorescence navigation is a novel technique for accurately identifying hepatocellular carcinoma(HCC)lesions during hepatectomy,enabling real-time visualization.Indocyanine green-based fluorescence guidance has been commonly used to demarcate HCC lesion boundaries,but it cannot distinguish between benign and malignant liver tumors.This review focused on the clinical applications and limitations of indocyanine green,as well as recent advances in novel fluorescent probes for fluorescence-guided surgery of HCC.It covers traditional fluorescent imaging probes such as enzymes,reactive oxygen species,reactive sulfur species,and pH-sensitive probes,followed by an introduction to aggregation-induced emission probes.Aggregation-induced emission probes exhibit strong fluorescence,low background signals,excellent biocompatibility,and high photostability in the aggregate state,but show no fluorescence in dilute solutions.Design strategies for these probes may offer insights for developing novel fluorescent probes for the real-time identification and navigation of HCC during surgery.展开更多
Oral squamous cell carcinoma(OSCC)presents a substantial global health threat with high incidence and mortality rates.Locoregional recurrence remains a major challenge.Recent advancements in near-infrared(NIR)fluoresc...Oral squamous cell carcinoma(OSCC)presents a substantial global health threat with high incidence and mortality rates.Locoregional recurrence remains a major challenge.Recent advancements in near-infrared(NIR)fluorescenceguided surgery(FGS),particularly using Indocyanine Green(ICG),shows promise in enhancing both diagnostic precision and surgery guidance.ICG exploits the enhanced permeability and retention(EPR)effect,allowing it to accumulate in tumor tissue and guide surgical resection.However,the application of fluorescence imaging with ICG in the surgical treatment of OSCC is still in its early stages,lacking standardized protocols in indications,procedural guidelines,and delivery precautions.Herein,we summarized collaborative consensus among experts from multiple medical institutions and references from both domestic and international literature,as well as multicenter clinical studies on ICG-guided surgery for OSCC,aiming to provide guidance for clinical practices in OSCC surgical treatment with ICG.This consensus advocates for the widespread adoption of ICG-guided surgery to improve surgical navigation,tumor margin delineation and efficiency of pathological assessment in OSCC treatment.展开更多
Fluorescence-guided surgery(FGS)with tumor-targeted imaging agents,particularly those using the near-infrared wavelength,has emerged as a real-time technique to highlight the tumor location and margins during a surgic...Fluorescence-guided surgery(FGS)with tumor-targeted imaging agents,particularly those using the near-infrared wavelength,has emerged as a real-time technique to highlight the tumor location and margins during a surgical procedure.For accurate visualization of prostate cancer(PCa)boundary and lymphatic metastasis,we developed a new approach involving an efficient self-quenched near-infrared fluorescence probe,Cy-KUE-OA,with dual PCa-membrane affinity.Cy-KUE-OA specifically targeted the prostate-specific membrane antigen(PSMA),anchored into the phospholipids of the cell membrane of PCa cells and consequently showed a strong Cy7-de-quenching effect.This dual–membrane-targeting probe allowed us to detect PSMA-expressing PCa cells both in vitro and in vivo and enabled clear visualization of the tumor boundary during fluorescence-guided laparoscopic surgery in PCa mouse models.Furthermore,the high PCa preference of Cy-KUE-OA was confirmed on surgically resected patient specimens of healthy tissues,PCa,and lymph node metastases.Taken together,our results serve as a bridge between preclinical and clinical research in FGS of PCa and lay a solid foundation for further clinical research.展开更多
Importance:Fluorescence-guided surgery(FGS)is a potentially powerful tool for hepatobiliary(HPB)surgery.The high sensitivity of fluorescence navigation is especially useful in settings where tactile feedback is limite...Importance:Fluorescence-guided surgery(FGS)is a potentially powerful tool for hepatobiliary(HPB)surgery.The high sensitivity of fluorescence navigation is especially useful in settings where tactile feedback is limited.Objective:The present narrative review evaluates literature on the use of FDA-approved fluorophores such as methylene blue(MB),5-aminolevulinic acid(5-ALA),and indocyanine green(ICG)for clinical intra-operative image-guidance during HPB surgery.Evidence Review:Approaches such as dosing,timing,imaging devices and comparative endpoints are summarized.The feasibility and safety of fluorophores in visualizing the biliary tree,identify biliary leaks,outline anatomic hepatic segments,identify tumors,and evaluate perfusion and graft function in liver transplants are discussed.Findings:Tumor-specific probes are a promising advancement in FGS with a greater degree of specificity.The current status of tumor-specific probes being evaluated in clinical trials are summarized.Conclusions and Relevance for Reviews:Relevant discussion of promising tumor-specific probes in pre-clinical development are discussed.Fluorescence-guidance in HPB surgery is relatively new,but current literature shows that the dyes are reliably able to outline desired structures with a variety of dosing,timing,and imaging devices to provide real-time intra-operative anatomic information to surgeons.Development of tumor-specific probes will further advance the field of HPB surgery especially during oncologic resections.展开更多
Surgical resection is the preferred option for hepatocellular carcinoma(HCC),but surgical navigation technology using indocyanine green still has some drawbacks such as non-specific imaging,thus it is very important t...Surgical resection is the preferred option for hepatocellular carcinoma(HCC),but surgical navigation technology using indocyanine green still has some drawbacks such as non-specific imaging,thus it is very important to develop newfluorescence imaging technology.All-cis hexaphenyl-1,3-butadiene derivative(ZZ-HPB-NC)with aggregation-induced emission(AIE)feature has been reported to be quickly turned-onfluorescent response in the intraoperative frozen-section slides of HCC.However,the probe did not respond to normal liver tissue around HCC.In order to enhance the diagnostic rate and elucidate the response mechanism,all-trans config-uration EE-HPB-NC,was furtherly synthesized.Within two minutes,non-cancer tissues could befluorescently labeled by EE-HPB-NC by spraying,showing the same effect with ZZ-HPB-NC to HCC.The results indicated that the configuration-induced cross-identificationfluorescence imaging strategy was achieved through the combination of ZZ-and EE-HPB-NC.Then the mechanism of HPB-NC localization in HCC lesions was explored,and the binding of HPB-NC with specific proteins in cells resulted in the AIE effect to label HCC cells.On this basis,the accuracy of specificfluorescence imaging for HCC was further verified on the mouse hepatic neoplasm models,indicating that it has clinical application potential for surgicalfluorescence real-time navigation.展开更多
Cancer is one of the main causes of death throughout the world.Radical elimination of tumor is crucial for a successful treatment.However,during cancer treatment,it is difficult to distinguish tumor boundaries with th...Cancer is one of the main causes of death throughout the world.Radical elimination of tumor is crucial for a successful treatment.However,during cancer treatment,it is difficult to distinguish tumor boundaries with the naked eye and to accurately exterminate it.In this work,based on the overexpression of H2S in some tumors,an activatable second near-infrared(NIR-Ⅱ)theranostic agent(NRS)for distinguishing tumor tissues from normal tissues,guiding surgical resection and ablating tumor tissues by efficient photothermal therapy is proposed.This developed probe NRS can emit fluorescence in the range of 900-1100 nm and detect tumor tissues with H2S overexpression.Under the guidance of NIR-Ⅱ fluorescence imaging,the tumor margins can be delineated clearly with high signal-to-background ratio.In addition,with the help of NIR-Ⅱ fluorescence surgery navigation,tumors tissues can be precisely resected.More importantly,the probe displays a high photothermal conversion efficiency and can efficiently induce tumor cells apoptosis under 808 nm laser irradiation.By using the desirable attributes of NRS,the tumor tissues with H2S overexpression was successfully ablated.This work provides a new tool for the future precision eradicate tumors without recurrence,which may have translational potential in biological and clinical systems.展开更多
Surgical tumor resection is a common approach to cancer treatment.India Ink tattoos are widely used to aid tumor resection by localizing and mapping the tumor edge at the surface.However,India Ink tattoos are easily o...Surgical tumor resection is a common approach to cancer treatment.India Ink tattoos are widely used to aid tumor resection by localizing and mapping the tumor edge at the surface.However,India Ink tattoos are easily obscured during electrosurgical resection,and fade in intensity over time.In this work,a novel near-infrared(NIR)fluorescent marker is introduced as an alternative.The NIR marker was made by mixing indocyanine green(ICG),biocompatible cyanoacrylate,and acetone.The marking strategy was evaluated in a chronic ex vivo feasibility study using porcine tissues,followed by a chronic in vivo mouse study while compared with India Ink.In both studies,signal-to-noise(SNR)ratios and dimensions of the NIR markers and/or India Ink over the study period were calculated and reported.Electrocautery was performed on the last day of the mouse study after mice were euthanized,and SNR ratios and dimensions were quantified and compared.Biopsy was performed at all injection sites and slides were examined by a pathologist.The proposed NIR marker achieved(i)consistent visibility in the 26-day feasibility study and(ii)improved durability,visibility,and biocompatibility when compared to traditional India Ink over the six-week period in an in vivo mouse model.These effects persist after electrocautery whereas the India Ink markers were obscured.The use of a NIR fluorescent presurgical marking strategy has the potential for intraoperative tracking during long-term treatment protocols.展开更多
In this editorial we comment on the article by Kalayarasan and co-workers published in the recent issue of the World Journal of Gastrointestinal Surgery.The authors present an interesting review on the use of indocyan...In this editorial we comment on the article by Kalayarasan and co-workers published in the recent issue of the World Journal of Gastrointestinal Surgery.The authors present an interesting review on the use of indocyanine green fluo-rescence in different aspects of abdominal surgery.They also highlight future perspectives of the use of indocyanine green in mini-invasive surgery.Indo-cyanine green,used for fluorescence imaging,has been approved by the Food and Drug Administration and is safe for use in humans.It can be administered in-travenously or intra-arterially.Since its advent,there have been several advance-ments in the applications of indocyanine green,especially in the surgical field,such as intraoperative mapping and biopsy of sentinel lymph node,measurement of hepatic function prior to resection,in neurosurgical cases to detect vascular anomalies,in cardiovascular cases for patency and assessment of vascular ab-normalities,in predicting healing following amputations,in helping visualization of hepatobiliary anatomy and blood vessels,in reconstructive surgery,to assess flap viability and for the evaluation of tissue perfusion following major trauma and burns.For these reasons,the intraoperative use of indocyanine green has become common in a variety of surgical specialties and transplant surgery.Co-lorectal surgery has just lately begun to adopt this technique,particularly for perfusion visualization to prevent anastomotic leakage.The regular use of in-docyanine green coupled with fluorescence angiography has recently been pro-posed as a feasible tool to help improve patient outcomes.Using the best available data,it has been shown that routine use of indocyanine green in colorectal surgery reduces the rates of anastomotic leak.The use of indocyanine green is proven to be safe,feasible,and effective in both elective and emergency scenarios.However,additional robust evidence from larger-scale,high-quality studies is essential before incorporating indocyanine green guided surgery into standard practice.展开更多
Advances in machine learning,computer vision and artificial intelligence methods,in combination with those in processing and cloud computing capability,portend the advent of true decision support during interventions ...Advances in machine learning,computer vision and artificial intelligence methods,in combination with those in processing and cloud computing capability,portend the advent of true decision support during interventions in real-time and soon perhaps in automated surgical steps.Such capability,deployed alongside technology intraoperatively,is termed digital surgery and can be delivered without the need for high-end capital robotic investment.An area close to clinical usefulness right now harnesses advances in near infrared endolaparoscopy and fluorescence guidance for tissue characterisation through the use of biophysics-inspired algorithms.This represents a potential synergistic methodology for the deep learning methods currently advancing in ophthalmology,radiology,and recently gastroenterology via colonoscopy.As databanks of more general surgical videos are created,greater analytic insights can be derived across the operative spectrum of gastroenterological disease and operations(including instrumentation and operative step sequencing and recognition,followed over time by surgeon and instrument performance assessment)and linked to value-based outcomes.However,issues of legality,ethics and even morality need consideration,as do the limiting effects of monopolies,cartels and isolated data silos.Furthermore,the role of the surgeon,surgical societies and healthcare institutions in this evolving field needs active deliberation,as the default risks relegation to bystander or passive recipient.This editorial provides insight into this accelerating field by illuminating the nearfuture and next decade evolutionary steps towards widespread clinical integration for patient and societal benefit.展开更多
AIM: To assess whether the addition of a customized, active immunotherapy to standard of care including fluorescence-guided surgery, may provide hints of an improved survival for patients with poor-prognosis, incurabl...AIM: To assess whether the addition of a customized, active immunotherapy to standard of care including fluorescence-guided surgery, may provide hints of an improved survival for patients with poor-prognosis, incurable glioblastoma multiform. METHODS: Preliminary to our ongoing, phase-Ⅱ clinical trial, we conducted a small pilot study enrolling five consecutive patients with resectable glioblastoma. In terms of Recursive Partitioning Analysis, four patientswere class Ⅴ and one was class Ⅳ. In all five cases, fluorescence-guided surgery was employed, followed by rapid steroid discontinuation. Patients were then treated with a combination of standard radio-chemotherapy with temozolomide and tumor lysate-pulsed, mature dendritic cell-based vaccinations.RESULTS: Though all five patients ultimately progressed, with any further treatment left to the sole decision of the treating oncologist, active immunotherapy was very well tolerated and induced specific immune responses in all three patients for whom enough material was available for such an assessment. Median progression-free survival was 16.1 mo. Even more important, median and mean overall survival were 27 mo and 26 mo, respectively. Three patients have died with an overall survival of 9 mo, 27 mo and 27.4 mo, while the other two are still alive at 32 mo and 36 mo, the former receiving treatment with bevacizumab, while the latter has now been off therapy for 12 mo. Four of five patients were alive at two years.CONCLUSION: Active immunotherapy with tumor lysate-pulsed, autologous dendritic cells is feasible, safe, well tolerated and biologically efficacious. A phase-Ⅱ study is ongoing to possibly improve further on our very encouraging clinical results.展开更多
Osteosarcoma(OS)is characterized by an unfavorable prognosis and high mortality rates,with the local recurrence attributed to residual lesions post-surgery being a major reason for treatment failure.Precise and tumor-...Osteosarcoma(OS)is characterized by an unfavorable prognosis and high mortality rates,with the local recurrence attributed to residual lesions post-surgery being a major reason for treatment failure.Precise and tumor-specific resection guidance to minimize recurrence remains a significant challenge.In the present study,a nanosystem based on aggregation-induced emission(AIE)molecules with emission in the second near-infrared window is proposed for the synergistic fluorescence(FL)and chemiluminescence(CL)imaging-guided surgical resection for the elimination of tumor foci.The designed AIE molecule,BBTD14,exhibits stable FL with a high quantum yield of up to 3.95%,which effectively matches the energy levels of CL high-energy states,generating the longest emission wavelength of CL reported to date.Targeted tumor imaging-guided surgery(IGS)is facilitated by FL and CL nanoprobes(FLNP and CLNP)constructed based on BBTD14.During OS surgery,the FLNP,with the stability of FL and a high targeting capability,was first intravenously used to guide the surgical removal of the main tumor.Subsequently,CLNP was locally incubated to facilitate rapid and accurate evaluation of residual tumors at the operative border.High signal-to-noise ratio CL imaging was achieved after spraying with hydrogen peroxide,thereby overcoming the limitations of intraoperative frozen sections.The proposed technique also significantly reduced the recurrence rates in OS mouse models and exhibited high marker specificity in ex vivo OS patient pathology samples,confirming its potential in clinical applications and providing a unique perspective for developing IGS.展开更多
Real-time intraoperative guidance is indispensable for ensuring complete and safe tumor resection during oncological surgery.Activatable fluorescence probes have demonstrated promise in guiding surgery during intricat...Real-time intraoperative guidance is indispensable for ensuring complete and safe tumor resection during oncological surgery.Activatable fluorescence probes have demonstrated promise in guiding surgery during intricate procedures,offering high-contrast images with the“turn-on”fluorescence signal upon reaction with tumor markers.However,single-factor activatable probes still encounter the limitation of potentially generating“false positive”results in the complex in vivo environment.Herein,we have developed a dualfactor recognition activatable probe,NBD-BDP-E,to further enhance specificity to tumors via a cascade process.The incorporation of an epidermal growth factor receptor(EGFR)inhibitor,erlotinib,in the probe ensures tumor recognition and accelerated cellular uptake firstly.Following the probe response to the high concentration of Glutathione in cells,molecular fluorescence emission is restored for fluorescence image guidance.Ultimately,the d-PeT-based activatable probe,NBD-BDP-E,exhibited the ability to light up an EGFR-overexpressed tumor tissue accurately with a superior tumor-to-normal tissue ratio for image-guided surgery via in situ spraying.Moreover,it shows the ability to image tumor tissue about 1 mm in diameter,highlighting the potential for this probe to be used as a tool in surgical resection.展开更多
基金supported by the National Natural Science Foundation of China grant(Nos.22174105 and 21974104)the National Key R&D Program of China(No.2020YFA0908800)。
文摘Owing to the high spatiotemporal resolution,the second near-infrared(NIR-II)imaging window can provide high imaging contrast with diminished tissue autofluorescence and suppressed photon scattering to pinpoint the locations for tumor surgery.Due to the unique optical properties and excellent fluorescence performance,quantum dots(QDs)are regarded as ideal nanoprobes for fluorescence-guided surgery(FGS).Moreover,QDs can be excited by a variety of light sources owing to the continuous and wide absorption ranges.Herein,light-emitting diode(LED)was used as the excitation source of QDs-based nanoprobes to realize FGS of tumor with high resolution.Since the LED light could irradiate a large region with consistent light intensity,signal distortion at the edge of imaging field was avoided.The signal intensity of the view edges under LED excitation can be improved by about 5 times compared to laser excitation.Therefore,more micro-vessels and smaller tumors(Vtumor<5 mm^(2))could be detected,thus providing more precise guidance for tumor resection surgery.
基金supported by the National Natural Science Foundation of China(Grants 82170642,82172754,81874208,22405079)the Opening Project of Hubei Key Laboratory of Purification and Application of Plant Anti-cancer Active Ingredients(HLPAI2023001).
文摘Fluorescence navigation is a novel technique for accurately identifying hepatocellular carcinoma(HCC)lesions during hepatectomy,enabling real-time visualization.Indocyanine green-based fluorescence guidance has been commonly used to demarcate HCC lesion boundaries,but it cannot distinguish between benign and malignant liver tumors.This review focused on the clinical applications and limitations of indocyanine green,as well as recent advances in novel fluorescent probes for fluorescence-guided surgery of HCC.It covers traditional fluorescent imaging probes such as enzymes,reactive oxygen species,reactive sulfur species,and pH-sensitive probes,followed by an introduction to aggregation-induced emission probes.Aggregation-induced emission probes exhibit strong fluorescence,low background signals,excellent biocompatibility,and high photostability in the aggregate state,but show no fluorescence in dilute solutions.Design strategies for these probes may offer insights for developing novel fluorescent probes for the real-time identification and navigation of HCC during surgery.
基金supported by National Natural Science Foundation of China(82072980)Research Grants(21015800800)from Science and Technology Commission of ShanghaiClinical Research Special Project(202040327)from Municipal Health Commission of Shanghai.
文摘Oral squamous cell carcinoma(OSCC)presents a substantial global health threat with high incidence and mortality rates.Locoregional recurrence remains a major challenge.Recent advancements in near-infrared(NIR)fluorescenceguided surgery(FGS),particularly using Indocyanine Green(ICG),shows promise in enhancing both diagnostic precision and surgery guidance.ICG exploits the enhanced permeability and retention(EPR)effect,allowing it to accumulate in tumor tissue and guide surgical resection.However,the application of fluorescence imaging with ICG in the surgical treatment of OSCC is still in its early stages,lacking standardized protocols in indications,procedural guidelines,and delivery precautions.Herein,we summarized collaborative consensus among experts from multiple medical institutions and references from both domestic and international literature,as well as multicenter clinical studies on ICG-guided surgery for OSCC,aiming to provide guidance for clinical practices in OSCC surgical treatment with ICG.This consensus advocates for the widespread adoption of ICG-guided surgery to improve surgical navigation,tumor margin delineation and efficiency of pathological assessment in OSCC treatment.
基金supported by the National Natural Science Foundation of China(NSFC)projects(22122705,22077139 and 81972400)CAMS Innovation Fund for Medical Sciences(CIFMS)(2021-I2M-1-054 and 2021-I2M-1-015)Beijing Outstanding Young Scientist Program(BJJWZYJH01201910023028,China).
文摘Fluorescence-guided surgery(FGS)with tumor-targeted imaging agents,particularly those using the near-infrared wavelength,has emerged as a real-time technique to highlight the tumor location and margins during a surgical procedure.For accurate visualization of prostate cancer(PCa)boundary and lymphatic metastasis,we developed a new approach involving an efficient self-quenched near-infrared fluorescence probe,Cy-KUE-OA,with dual PCa-membrane affinity.Cy-KUE-OA specifically targeted the prostate-specific membrane antigen(PSMA),anchored into the phospholipids of the cell membrane of PCa cells and consequently showed a strong Cy7-de-quenching effect.This dual–membrane-targeting probe allowed us to detect PSMA-expressing PCa cells both in vitro and in vivo and enabled clear visualization of the tumor boundary during fluorescence-guided laparoscopic surgery in PCa mouse models.Furthermore,the high PCa preference of Cy-KUE-OA was confirmed on surgically resected patient specimens of healthy tissues,PCa,and lymph node metastases.Taken together,our results serve as a bridge between preclinical and clinical research in FGS of PCa and lay a solid foundation for further clinical research.
基金This work was supported by US National Cancer Institute grant numbers CA126023,CA142669(MB and AntiCancer,Inc.)VA Merit Review grant number 1 I01 BX003856-01A1(MB)NIH/NCI T32CA121938(TM Lwin).
文摘Importance:Fluorescence-guided surgery(FGS)is a potentially powerful tool for hepatobiliary(HPB)surgery.The high sensitivity of fluorescence navigation is especially useful in settings where tactile feedback is limited.Objective:The present narrative review evaluates literature on the use of FDA-approved fluorophores such as methylene blue(MB),5-aminolevulinic acid(5-ALA),and indocyanine green(ICG)for clinical intra-operative image-guidance during HPB surgery.Evidence Review:Approaches such as dosing,timing,imaging devices and comparative endpoints are summarized.The feasibility and safety of fluorophores in visualizing the biliary tree,identify biliary leaks,outline anatomic hepatic segments,identify tumors,and evaluate perfusion and graft function in liver transplants are discussed.Findings:Tumor-specific probes are a promising advancement in FGS with a greater degree of specificity.The current status of tumor-specific probes being evaluated in clinical trials are summarized.Conclusions and Relevance for Reviews:Relevant discussion of promising tumor-specific probes in pre-clinical development are discussed.Fluorescence-guidance in HPB surgery is relatively new,but current literature shows that the dyes are reliably able to outline desired structures with a variety of dosing,timing,and imaging devices to provide real-time intra-operative anatomic information to surgeons.Development of tumor-specific probes will further advance the field of HPB surgery especially during oncologic resections.
基金National Natural Science Foundation of China,Grant/Award Numbers:82172754,81874208Opening Project of Hubei Key Laboratory of Purification and Application of Plant Anti-cancer Active Ingredients,Grant/Award Number:HLPAI2023001。
文摘Surgical resection is the preferred option for hepatocellular carcinoma(HCC),but surgical navigation technology using indocyanine green still has some drawbacks such as non-specific imaging,thus it is very important to develop newfluorescence imaging technology.All-cis hexaphenyl-1,3-butadiene derivative(ZZ-HPB-NC)with aggregation-induced emission(AIE)feature has been reported to be quickly turned-onfluorescent response in the intraoperative frozen-section slides of HCC.However,the probe did not respond to normal liver tissue around HCC.In order to enhance the diagnostic rate and elucidate the response mechanism,all-trans config-uration EE-HPB-NC,was furtherly synthesized.Within two minutes,non-cancer tissues could befluorescently labeled by EE-HPB-NC by spraying,showing the same effect with ZZ-HPB-NC to HCC.The results indicated that the configuration-induced cross-identificationfluorescence imaging strategy was achieved through the combination of ZZ-and EE-HPB-NC.Then the mechanism of HPB-NC localization in HCC lesions was explored,and the binding of HPB-NC with specific proteins in cells resulted in the AIE effect to label HCC cells.On this basis,the accuracy of specificfluorescence imaging for HCC was further verified on the mouse hepatic neoplasm models,indicating that it has clinical application potential for surgicalfluorescence real-time navigation.
基金financially supported by National Natural Science Foundation of China(Nos.22406099,82172961,22077048 and22277014)the Special Fund of Taishan Scholars Project of Shandong Province(No.tsqnz20231253)+2 种基金Guangxi Natural Science Foundation(Nos.2021GXNSFDA075003,AD21220061)the startup fund of Guangxi University(No.A3040051003)the Major Science and Technology Plan Project of Hainan Province(No.ZDKJ202005)。
文摘Cancer is one of the main causes of death throughout the world.Radical elimination of tumor is crucial for a successful treatment.However,during cancer treatment,it is difficult to distinguish tumor boundaries with the naked eye and to accurately exterminate it.In this work,based on the overexpression of H2S in some tumors,an activatable second near-infrared(NIR-Ⅱ)theranostic agent(NRS)for distinguishing tumor tissues from normal tissues,guiding surgical resection and ablating tumor tissues by efficient photothermal therapy is proposed.This developed probe NRS can emit fluorescence in the range of 900-1100 nm and detect tumor tissues with H2S overexpression.Under the guidance of NIR-Ⅱ fluorescence imaging,the tumor margins can be delineated clearly with high signal-to-background ratio.In addition,with the help of NIR-Ⅱ fluorescence surgery navigation,tumors tissues can be precisely resected.More importantly,the probe displays a high photothermal conversion efficiency and can efficiently induce tumor cells apoptosis under 808 nm laser irradiation.By using the desirable attributes of NRS,the tumor tissues with H2S overexpression was successfully ablated.This work provides a new tool for the future precision eradicate tumors without recurrence,which may have translational potential in biological and clinical systems.
基金This work is spported by the National Istitutes of Health under award rumbers 1RO1BB020610 and R21EB024707spprted by the Intramua Research Progam of the National Insites of Health,Natioial Cancer Istitutet Center for Cancer Reearch.
文摘Surgical tumor resection is a common approach to cancer treatment.India Ink tattoos are widely used to aid tumor resection by localizing and mapping the tumor edge at the surface.However,India Ink tattoos are easily obscured during electrosurgical resection,and fade in intensity over time.In this work,a novel near-infrared(NIR)fluorescent marker is introduced as an alternative.The NIR marker was made by mixing indocyanine green(ICG),biocompatible cyanoacrylate,and acetone.The marking strategy was evaluated in a chronic ex vivo feasibility study using porcine tissues,followed by a chronic in vivo mouse study while compared with India Ink.In both studies,signal-to-noise(SNR)ratios and dimensions of the NIR markers and/or India Ink over the study period were calculated and reported.Electrocautery was performed on the last day of the mouse study after mice were euthanized,and SNR ratios and dimensions were quantified and compared.Biopsy was performed at all injection sites and slides were examined by a pathologist.The proposed NIR marker achieved(i)consistent visibility in the 26-day feasibility study and(ii)improved durability,visibility,and biocompatibility when compared to traditional India Ink over the six-week period in an in vivo mouse model.These effects persist after electrocautery whereas the India Ink markers were obscured.The use of a NIR fluorescent presurgical marking strategy has the potential for intraoperative tracking during long-term treatment protocols.
文摘In this editorial we comment on the article by Kalayarasan and co-workers published in the recent issue of the World Journal of Gastrointestinal Surgery.The authors present an interesting review on the use of indocyanine green fluo-rescence in different aspects of abdominal surgery.They also highlight future perspectives of the use of indocyanine green in mini-invasive surgery.Indo-cyanine green,used for fluorescence imaging,has been approved by the Food and Drug Administration and is safe for use in humans.It can be administered in-travenously or intra-arterially.Since its advent,there have been several advance-ments in the applications of indocyanine green,especially in the surgical field,such as intraoperative mapping and biopsy of sentinel lymph node,measurement of hepatic function prior to resection,in neurosurgical cases to detect vascular anomalies,in cardiovascular cases for patency and assessment of vascular ab-normalities,in predicting healing following amputations,in helping visualization of hepatobiliary anatomy and blood vessels,in reconstructive surgery,to assess flap viability and for the evaluation of tissue perfusion following major trauma and burns.For these reasons,the intraoperative use of indocyanine green has become common in a variety of surgical specialties and transplant surgery.Co-lorectal surgery has just lately begun to adopt this technique,particularly for perfusion visualization to prevent anastomotic leakage.The regular use of in-docyanine green coupled with fluorescence angiography has recently been pro-posed as a feasible tool to help improve patient outcomes.Using the best available data,it has been shown that routine use of indocyanine green in colorectal surgery reduces the rates of anastomotic leak.The use of indocyanine green is proven to be safe,feasible,and effective in both elective and emergency scenarios.However,additional robust evidence from larger-scale,high-quality studies is essential before incorporating indocyanine green guided surgery into standard practice.
基金by Disruptive Technologies and Innovation Fund,Enterprise Ireland,Ireland.
文摘Advances in machine learning,computer vision and artificial intelligence methods,in combination with those in processing and cloud computing capability,portend the advent of true decision support during interventions in real-time and soon perhaps in automated surgical steps.Such capability,deployed alongside technology intraoperatively,is termed digital surgery and can be delivered without the need for high-end capital robotic investment.An area close to clinical usefulness right now harnesses advances in near infrared endolaparoscopy and fluorescence guidance for tissue characterisation through the use of biophysics-inspired algorithms.This represents a potential synergistic methodology for the deep learning methods currently advancing in ophthalmology,radiology,and recently gastroenterology via colonoscopy.As databanks of more general surgical videos are created,greater analytic insights can be derived across the operative spectrum of gastroenterological disease and operations(including instrumentation and operative step sequencing and recognition,followed over time by surgeon and instrument performance assessment)and linked to value-based outcomes.However,issues of legality,ethics and even morality need consideration,as do the limiting effects of monopolies,cartels and isolated data silos.Furthermore,the role of the surgeon,surgical societies and healthcare institutions in this evolving field needs active deliberation,as the default risks relegation to bystander or passive recipient.This editorial provides insight into this accelerating field by illuminating the nearfuture and next decade evolutionary steps towards widespread clinical integration for patient and societal benefit.
基金Supported by Spanish Health Ministry Grant MCI EC08/00186
文摘AIM: To assess whether the addition of a customized, active immunotherapy to standard of care including fluorescence-guided surgery, may provide hints of an improved survival for patients with poor-prognosis, incurable glioblastoma multiform. METHODS: Preliminary to our ongoing, phase-Ⅱ clinical trial, we conducted a small pilot study enrolling five consecutive patients with resectable glioblastoma. In terms of Recursive Partitioning Analysis, four patientswere class Ⅴ and one was class Ⅳ. In all five cases, fluorescence-guided surgery was employed, followed by rapid steroid discontinuation. Patients were then treated with a combination of standard radio-chemotherapy with temozolomide and tumor lysate-pulsed, mature dendritic cell-based vaccinations.RESULTS: Though all five patients ultimately progressed, with any further treatment left to the sole decision of the treating oncologist, active immunotherapy was very well tolerated and induced specific immune responses in all three patients for whom enough material was available for such an assessment. Median progression-free survival was 16.1 mo. Even more important, median and mean overall survival were 27 mo and 26 mo, respectively. Three patients have died with an overall survival of 9 mo, 27 mo and 27.4 mo, while the other two are still alive at 32 mo and 36 mo, the former receiving treatment with bevacizumab, while the latter has now been off therapy for 12 mo. Four of five patients were alive at two years.CONCLUSION: Active immunotherapy with tumor lysate-pulsed, autologous dendritic cells is feasible, safe, well tolerated and biologically efficacious. A phase-Ⅱ study is ongoing to possibly improve further on our very encouraging clinical results.
基金supported by Sponsored by the National Natural Science Foundation of China(82373177 and 82001945)Shanghai Sailing Program(23YF1434400)+4 种基金Shanghai Jiao Tong University“SJTU Star”Medical Engineering Interdisciplinary Research Fund(YG2023LC09)the starting grant of ShanghaiTech University,and Shanghai Clinical Research and Trial Centerthe Centre for High-resolution Electron Microscopy(ChEM),School of Physical Science and Technology,ShanghaiTech University(No.EM02161943)for the characterization supportthe Dr.Rong Gao and Analytical Instrumentation Center(#SPST-AIC10112914)School of Physical Science and Technology,ShanghaiTech University for the spectral test support.
文摘Osteosarcoma(OS)is characterized by an unfavorable prognosis and high mortality rates,with the local recurrence attributed to residual lesions post-surgery being a major reason for treatment failure.Precise and tumor-specific resection guidance to minimize recurrence remains a significant challenge.In the present study,a nanosystem based on aggregation-induced emission(AIE)molecules with emission in the second near-infrared window is proposed for the synergistic fluorescence(FL)and chemiluminescence(CL)imaging-guided surgical resection for the elimination of tumor foci.The designed AIE molecule,BBTD14,exhibits stable FL with a high quantum yield of up to 3.95%,which effectively matches the energy levels of CL high-energy states,generating the longest emission wavelength of CL reported to date.Targeted tumor imaging-guided surgery(IGS)is facilitated by FL and CL nanoprobes(FLNP and CLNP)constructed based on BBTD14.During OS surgery,the FLNP,with the stability of FL and a high targeting capability,was first intravenously used to guide the surgical removal of the main tumor.Subsequently,CLNP was locally incubated to facilitate rapid and accurate evaluation of residual tumors at the operative border.High signal-to-noise ratio CL imaging was achieved after spraying with hydrogen peroxide,thereby overcoming the limitations of intraoperative frozen sections.The proposed technique also significantly reduced the recurrence rates in OS mouse models and exhibited high marker specificity in ex vivo OS patient pathology samples,confirming its potential in clinical applications and providing a unique perspective for developing IGS.
基金supported by National Natural Science Foundation of China(grant nos.21925802 and 22338005)Liaoning Binhai Laboratory(grant no.LBLB-2023-03)the Fundamental Research Funds for the Central Universities(grant no.DUT22LAB601).
文摘Real-time intraoperative guidance is indispensable for ensuring complete and safe tumor resection during oncological surgery.Activatable fluorescence probes have demonstrated promise in guiding surgery during intricate procedures,offering high-contrast images with the“turn-on”fluorescence signal upon reaction with tumor markers.However,single-factor activatable probes still encounter the limitation of potentially generating“false positive”results in the complex in vivo environment.Herein,we have developed a dualfactor recognition activatable probe,NBD-BDP-E,to further enhance specificity to tumors via a cascade process.The incorporation of an epidermal growth factor receptor(EGFR)inhibitor,erlotinib,in the probe ensures tumor recognition and accelerated cellular uptake firstly.Following the probe response to the high concentration of Glutathione in cells,molecular fluorescence emission is restored for fluorescence image guidance.Ultimately,the d-PeT-based activatable probe,NBD-BDP-E,exhibited the ability to light up an EGFR-overexpressed tumor tissue accurately with a superior tumor-to-normal tissue ratio for image-guided surgery via in situ spraying.Moreover,it shows the ability to image tumor tissue about 1 mm in diameter,highlighting the potential for this probe to be used as a tool in surgical resection.
