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
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
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
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
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
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
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.
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.
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.
