Technological improvements are crucial in the evolution of surgery.Real-time fluorescence-guided surgery(FGS)has spread worldwide,mainly because of its usefulness during the intraoperative decision-making processes.Th...Technological improvements are crucial in the evolution of surgery.Real-time fluorescence-guided surgery(FGS)has spread worldwide,mainly because of its usefulness during the intraoperative decision-making processes.The success of any gastrointestinal oncologic resection is based on the anatomical identification of the primary tumor and its regional lymph nodes.FGS allows also to evaluate the blood perfusion at the gastrointestinal stumps after colorectal or esophageal resections.Therefore,a reduction on the anastomotic leak rates has been postulated as one of the foreseeable benefits provided by the use of FGS in these procedures.Although the use of fluorescence in lymph node detection was initially described in breast cancer surgery,the technique is currently applied in gastric or splenic flexure cancers,as they both present complex and variable lymphatic drainages.FGS allows also to perform intraoperative lymphograms or sentinel lymph node biopsies.New applications of FGS are being developed to assist in the detection of peritoneal metastases or in the evaluation of the tumor resection margins.The present review aims to provide a general overview of the current status of real-time FGS in gastrointestinal oncologic surgery.We put a special focus on the different applications of FGS,discussing the main findings and limitations found in the contemporary literature and also the promising near future applications.展开更多
A 67-year-old female presented with unexplained abdominal pain. A contrast-enhanced computed tomography scan of the abdomen incidentally revealed a mass in the uncinate process of the pancreas. This mass was resected ...A 67-year-old female presented with unexplained abdominal pain. A contrast-enhanced computed tomography scan of the abdomen incidentally revealed a mass in the uncinate process of the pancreas. This mass was resected and based on histopathological findings, diagnosed as a solitary fibrous tumor (SFT) of the pancreas. A SFT is an extremely rare benign mesenchymal tumor that in 65% of cases affects the visceral pleura but can also affect extra-pleural sites. The intraoperative demarcation of pancreatic tumors, such as SFTs, can bechallenging. In this report, the first clear intraoperative identification of a SFT of the pancreas in a human was shown using near-infrared fluorescence and methylene blue.展开更多
AIM: To investigate feasibility and accuracy of near-infrared fluorescence imaging using indocyanine green: nanocolloid for sentinel lymph node (SLN) detection in gastric cancer.METHODS: A prospective, single-institut...AIM: To investigate feasibility and accuracy of near-infrared fluorescence imaging using indocyanine green: nanocolloid for sentinel lymph node (SLN) detection in gastric cancer.METHODS: A prospective, single-institution, phase I feasibility trial was conducted. Patients suffering from gastric cancer and planned for gastrectomy were included. During surgery, a subserosal injection of 1.6 mL ICG:Nanocoll was administered around the tumor. NIR fluorescence imaging of the abdominal cavity was performed using the Mini-FLARE™ NIR fluorescence imaging system. Lymphatic pathways and SLNs were visualized. Of every detected SLN, the corresponding lymph node station, signal-to-background ratio and histopathological diagnosis was determined. Patients underwent standard-of-care gastrectomy. Detected SLNs outside the standard dissection planes were also resected and evaluated.RESULTS: Twenty-six patients were enrolled. Four patients were excluded because distant metastases were found during surgery or due to technical failure of the injection. In 21 of the remaining 22 patients, at least 1 SLN was detected by NIR Fluorescence imaging (mean 3.1 SLNs; range 1-6). In 8 of the 21 patients, tumor-positive LNs were found. Overall accuracy of the technique was 90% (70%-99%; 95%CI), which decreased by higher pT-stage (100%, 100%, 100%, 90%, 0% for respectively Tx, T1, T2, T3, T4 tumors). All NIR-negative SLNs were completely effaced by tumor. Mean fluorescence signal-to-background ratio of SLNs was 4.4 (range 1.4-19.8). In 8 of the 21 patients, SLNs outside the standard resection plane were identified, that contained malignant cells in 2 patients.CONCLUSION: This study shows successful use of ICG:Nanocoll as lymphatic tracer for SLN detection in gastric cancer. Moreover, tumor-containing LNs outside the standard dissection planes were identified.展开更多
Phototheranostic with highly integrated functions is an attractive platform for cancer management. It remains challenging to develop a facile phototheranostic platform with complementary bimodal imaging and combinatio...Phototheranostic with highly integrated functions is an attractive platform for cancer management. It remains challenging to develop a facile phototheranostic platform with complementary bimodal imaging and combinational therapy capacity. Herein, the small-molecule cyanine IR780 loaded liposomes have been harnessed as a nanoplatform to simultaneously realize photoacoustic(PA)/the second near-infrared window(NIR-Ⅱ) fluorescence imaging and image-guided surgery/adjuvant photothermal therapy(PTT).This nanoplatform exhibits attractive properties like uniform controllable size, stable dispersibility, NIR-Ⅱ fluorescence emission, photothermal conversion, and biocompatibility. Benefiting from the complementary PA/NIR-Ⅱ fluorescence bimodal imaging, this nanoplatform was successfully applied in precise vasculature delineation and tumor diagnosis. Interestingly, the tumor was clearly detected by NIR-Ⅱ fluorescence imaging with the highest tumor-to-normal-tissue ratio up to 12.69, while signal interference from the liver was significantly reduced, due to the difference in the elimination rate of the nanoplatform in the liver and tumor. Under the precise guidance of the image, the tumor was accurately resected, and the simulated residual lesion after surgery was completely ablated by adjuvant PTT. This combined therapy showed improved antitumor efcacy over the individual surgery or PTT. This work develops a facile phototheranostic nanoplatform with great significance in accurately diagnosing and effectively treating tumors using simple NIR light irradiation.展开更多
Development of efficient fluorescent probes that can realize precise fluorescence image-guided cancer surgery(FIGCS)with extremely high tumor-to-normal tissue(T/NT)ratio is urgently desirable.Herein,we report the desi...Development of efficient fluorescent probes that can realize precise fluorescence image-guided cancer surgery(FIGCS)with extremely high tumor-to-normal tissue(T/NT)ratio is urgently desirable.Herein,we report the design and synthesis of an aggregation-induced emission(AIE)-active,peptide-based fluorescence turn-on probe MPA-Ph-R-FFGYSAYPDSVPMMS(MPA-Ph-R-FFGYSA for short),which consists of a new near-infrared emissive AIE luminogen(AIEgen)MPA-Ph-R,a self-assembling peptide sequence“FFG”,and an“active”targeting peptide YSAYPDSVPMMS that can selectively bind to EphA2 protein cluster overexpressed in many cancers.As compared to the control probe MPA-Ph-R-YSA without“FFG”,MPA-Ph-R-FFGYSA exhibits much higher fluorescent brightness and sensitivity in both cellular and in vivo studies on EphA2 cluster detection/imaging,as“FFG”is beneficial to closer assembly of AIEgens in EphA2 cluster,leading to more effective restriction of the intramolecular motion of AIEgen.In vivo studies demonstrate that MPA-Ph-R-FFGYSA is a safe bioprobe and gives excellent performance in FIGCS with a rather high T/NT ratio of^13.4 upon intravenous administration into peritoneal carcinomatosis-bearing mice.This study provides a new strategy of utilizing the close assembly of tumor microenvironment-responsive AIE probes for boost FIGCS.展开更多
The rapid development of fluorescence imaging for intraoperative navigation has spurred further development of targeted fluorescent probes in the past decade.Only a few nontargeted dyes,including indocyanine green and...The rapid development of fluorescence imaging for intraoperative navigation has spurred further development of targeted fluorescent probes in the past decade.Only a few nontargeted dyes,including indocyanine green and methylene blue,are currently applied for fluorescence guided surgery in the clinic.While no targeted fluorescent probes have been approved for the clinic,a number of them have entered clinical trials.These probes have emission wavelengths in the visible and near infrared(NIR)-I(700-900 nm)range.Among them,activatable probes and nanoprobes have generated special interest.Compared with NIR-I fluorescent probes,NIR-II(1000-1700 nm)fluorescent probes exhibit better intravital performance in terms of increased penetration depths,reduced tissue autofluorescence,and higher signalto-background ratios.However,more challenges are expected before the successful translation of NIR-II probes from bench to bedside.This review provides a brief overview of targeted fluorescent probes under clinical evaluation and recent achievements in the field of NIR-II fluorescence imaging.In addition,we outline key considerations concerning the design of fluorescent probes for clinical translation.展开更多
Cutting-edge technologies in optical molecular imaging have ushered in new frontiers in cancer research, clinical translation, and medical practice, as evidenced by recent advances in optical multimodality imaging, Ce...Cutting-edge technologies in optical molecular imaging have ushered in new frontiers in cancer research, clinical translation, and medical practice, as evidenced by recent advances in optical multimodality imaging, Cerenkov luminescence imaging(CLI), and optical imageguided surgeries. New abilities allow in vivo cancer imaging with sensitivity and accuracy that are unprecedented in conventional imaging approaches. The visualization of cellular and molecular behaviors and events within tumors in living subjects is improving our deeper understanding of tumors at a systems level. These advances are being rapidly used to acquire tumor-to-tumor molecular heterogeneity, both dynamically and quantitatively, as well as to achieve more effective therapeutic interventions with the assistance of real-time imaging. In the era of molecular imaging, optical technologies hold great promise to facilitate the development of highly sensitive cancer diagnoses as well as personalized patient treatment—one of the ultimate goals of precision medicine.展开更多
文摘Technological improvements are crucial in the evolution of surgery.Real-time fluorescence-guided surgery(FGS)has spread worldwide,mainly because of its usefulness during the intraoperative decision-making processes.The success of any gastrointestinal oncologic resection is based on the anatomical identification of the primary tumor and its regional lymph nodes.FGS allows also to evaluate the blood perfusion at the gastrointestinal stumps after colorectal or esophageal resections.Therefore,a reduction on the anastomotic leak rates has been postulated as one of the foreseeable benefits provided by the use of FGS in these procedures.Although the use of fluorescence in lymph node detection was initially described in breast cancer surgery,the technique is currently applied in gastric or splenic flexure cancers,as they both present complex and variable lymphatic drainages.FGS allows also to perform intraoperative lymphograms or sentinel lymph node biopsies.New applications of FGS are being developed to assist in the detection of peritoneal metastases or in the evaluation of the tumor resection margins.The present review aims to provide a general overview of the current status of real-time FGS in gastrointestinal oncologic surgery.We put a special focus on the different applications of FGS,discussing the main findings and limitations found in the contemporary literature and also the promising near future applications.
基金Supported by (in part) NIH grant R01-CA-115296the Dutch Cancer Society grant UL2010-4732the Center for Trans-lational Molecular Medicine, project MUSIS (grant 03O-202)
文摘A 67-year-old female presented with unexplained abdominal pain. A contrast-enhanced computed tomography scan of the abdomen incidentally revealed a mass in the uncinate process of the pancreas. This mass was resected and based on histopathological findings, diagnosed as a solitary fibrous tumor (SFT) of the pancreas. A SFT is an extremely rare benign mesenchymal tumor that in 65% of cases affects the visceral pleura but can also affect extra-pleural sites. The intraoperative demarcation of pancreatic tumors, such as SFTs, can bechallenging. In this report, the first clear intraoperative identification of a SFT of the pancreas in a human was shown using near-infrared fluorescence and methylene blue.
文摘AIM: To investigate feasibility and accuracy of near-infrared fluorescence imaging using indocyanine green: nanocolloid for sentinel lymph node (SLN) detection in gastric cancer.METHODS: A prospective, single-institution, phase I feasibility trial was conducted. Patients suffering from gastric cancer and planned for gastrectomy were included. During surgery, a subserosal injection of 1.6 mL ICG:Nanocoll was administered around the tumor. NIR fluorescence imaging of the abdominal cavity was performed using the Mini-FLARE™ NIR fluorescence imaging system. Lymphatic pathways and SLNs were visualized. Of every detected SLN, the corresponding lymph node station, signal-to-background ratio and histopathological diagnosis was determined. Patients underwent standard-of-care gastrectomy. Detected SLNs outside the standard dissection planes were also resected and evaluated.RESULTS: Twenty-six patients were enrolled. Four patients were excluded because distant metastases were found during surgery or due to technical failure of the injection. In 21 of the remaining 22 patients, at least 1 SLN was detected by NIR Fluorescence imaging (mean 3.1 SLNs; range 1-6). In 8 of the 21 patients, tumor-positive LNs were found. Overall accuracy of the technique was 90% (70%-99%; 95%CI), which decreased by higher pT-stage (100%, 100%, 100%, 90%, 0% for respectively Tx, T1, T2, T3, T4 tumors). All NIR-negative SLNs were completely effaced by tumor. Mean fluorescence signal-to-background ratio of SLNs was 4.4 (range 1.4-19.8). In 8 of the 21 patients, SLNs outside the standard resection plane were identified, that contained malignant cells in 2 patients.CONCLUSION: This study shows successful use of ICG:Nanocoll as lymphatic tracer for SLN detection in gastric cancer. Moreover, tumor-containing LNs outside the standard dissection planes were identified.
基金financially supported in part by the National Natural Science Foundation of China(Nos.62075103,81973488)the Natural Science Foundation of Jiangsu Province(No.BK20211271)+4 种基金the Foundation of Anhui Province Key Laboratory of Pharmaceutical Preparation Technology and Application(No.2021KFKT07)the Training Program of Innovation and Entrepreneurship for College Students in Jiangsu(No.202110312037Z)the Jiangsu Provincial Medical Youth Talent(No.QNRC2016075)the Nanjing Medical Science and Technique Development Foundation(No.ZKX19022)the Jiangsu Provincial High level Health Talent“six one project”(No.LGY2019005)。
文摘Phototheranostic with highly integrated functions is an attractive platform for cancer management. It remains challenging to develop a facile phototheranostic platform with complementary bimodal imaging and combinational therapy capacity. Herein, the small-molecule cyanine IR780 loaded liposomes have been harnessed as a nanoplatform to simultaneously realize photoacoustic(PA)/the second near-infrared window(NIR-Ⅱ) fluorescence imaging and image-guided surgery/adjuvant photothermal therapy(PTT).This nanoplatform exhibits attractive properties like uniform controllable size, stable dispersibility, NIR-Ⅱ fluorescence emission, photothermal conversion, and biocompatibility. Benefiting from the complementary PA/NIR-Ⅱ fluorescence bimodal imaging, this nanoplatform was successfully applied in precise vasculature delineation and tumor diagnosis. Interestingly, the tumor was clearly detected by NIR-Ⅱ fluorescence imaging with the highest tumor-to-normal-tissue ratio up to 12.69, while signal interference from the liver was significantly reduced, due to the difference in the elimination rate of the nanoplatform in the liver and tumor. Under the precise guidance of the image, the tumor was accurately resected, and the simulated residual lesion after surgery was completely ablated by adjuvant PTT. This combined therapy showed improved antitumor efcacy over the individual surgery or PTT. This work develops a facile phototheranostic nanoplatform with great significance in accurately diagnosing and effectively treating tumors using simple NIR light irradiation.
基金This work was supported by the Tianjin Technical Expert Project(19JCTPJC41200)the National Natural Science Foundation of China(51873150,31770974)the National Key Research and Development Program of China(Intergovernmental Cooperation Project,2017YFE0132200).
文摘Development of efficient fluorescent probes that can realize precise fluorescence image-guided cancer surgery(FIGCS)with extremely high tumor-to-normal tissue(T/NT)ratio is urgently desirable.Herein,we report the design and synthesis of an aggregation-induced emission(AIE)-active,peptide-based fluorescence turn-on probe MPA-Ph-R-FFGYSAYPDSVPMMS(MPA-Ph-R-FFGYSA for short),which consists of a new near-infrared emissive AIE luminogen(AIEgen)MPA-Ph-R,a self-assembling peptide sequence“FFG”,and an“active”targeting peptide YSAYPDSVPMMS that can selectively bind to EphA2 protein cluster overexpressed in many cancers.As compared to the control probe MPA-Ph-R-YSA without“FFG”,MPA-Ph-R-FFGYSA exhibits much higher fluorescent brightness and sensitivity in both cellular and in vivo studies on EphA2 cluster detection/imaging,as“FFG”is beneficial to closer assembly of AIEgens in EphA2 cluster,leading to more effective restriction of the intramolecular motion of AIEgen.In vivo studies demonstrate that MPA-Ph-R-FFGYSA is a safe bioprobe and gives excellent performance in FIGCS with a rather high T/NT ratio of^13.4 upon intravenous administration into peritoneal carcinomatosis-bearing mice.This study provides a new strategy of utilizing the close assembly of tumor microenvironment-responsive AIE probes for boost FIGCS.
基金National Key Research and Development Program of China,Grant/Award Number:2016YFA0201400State Key Program of National Natural Science of China,Grant/Award Number:81930047+3 种基金Projects of International Cooperation and Exchanges NSFC-PSF,Grant/Award Number:31961143003National Project for Research and Development of Major Scientific Instruments,Grant/Award Number:81727803Beijing Natural Science Foundation,Haidian,Original Innovation Joint Fund,Grant/Award Number:17L20170Foundation for Innovative Research Groups of the National Natural Science Foundation of China,Grant/Award Number:81421004。
文摘The rapid development of fluorescence imaging for intraoperative navigation has spurred further development of targeted fluorescent probes in the past decade.Only a few nontargeted dyes,including indocyanine green and methylene blue,are currently applied for fluorescence guided surgery in the clinic.While no targeted fluorescent probes have been approved for the clinic,a number of them have entered clinical trials.These probes have emission wavelengths in the visible and near infrared(NIR)-I(700-900 nm)range.Among them,activatable probes and nanoprobes have generated special interest.Compared with NIR-I fluorescent probes,NIR-II(1000-1700 nm)fluorescent probes exhibit better intravital performance in terms of increased penetration depths,reduced tissue autofluorescence,and higher signalto-background ratios.However,more challenges are expected before the successful translation of NIR-II probes from bench to bedside.This review provides a brief overview of targeted fluorescent probes under clinical evaluation and recent achievements in the field of NIR-II fluorescence imaging.In addition,we outline key considerations concerning the design of fluorescent probes for clinical translation.
文摘Cutting-edge technologies in optical molecular imaging have ushered in new frontiers in cancer research, clinical translation, and medical practice, as evidenced by recent advances in optical multimodality imaging, Cerenkov luminescence imaging(CLI), and optical imageguided surgeries. New abilities allow in vivo cancer imaging with sensitivity and accuracy that are unprecedented in conventional imaging approaches. The visualization of cellular and molecular behaviors and events within tumors in living subjects is improving our deeper understanding of tumors at a systems level. These advances are being rapidly used to acquire tumor-to-tumor molecular heterogeneity, both dynamically and quantitatively, as well as to achieve more effective therapeutic interventions with the assistance of real-time imaging. In the era of molecular imaging, optical technologies hold great promise to facilitate the development of highly sensitive cancer diagnoses as well as personalized patient treatment—one of the ultimate goals of precision medicine.