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Han M, Lee YJ, Ahn J, Nam S, Kim M, Park J, Ahn J, Ryu H, Seo Y, Park B, Kim D, Kim C. A clinical feasibility study of a photoacoustic finder for sentinel lymph node biopsy in breast cancer patients: A prospective cross-sectional study. PHOTOACOUSTICS 2025; 43:100716. [PMID: 40236678 PMCID: PMC11999587 DOI: 10.1016/j.pacs.2025.100716] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/20/2025] [Revised: 03/10/2025] [Accepted: 03/21/2025] [Indexed: 04/17/2025]
Abstract
The sentinel lymph node (SLNb) is generally performed using radioisotopes, blue dyes, or both to improve false negative rate. However, ionizing radiation is involved in a gamma probe with radioisotopes and the blue dye detection relies on native visual inspection by an operator. To overcome these limitations, we developed the photoacoustic finder (PAF), a highly sensitive, non-radioactive detector that uses only blue dye and a photoacoustic signal to detect SLNs. A total of 121 patients with breast cancer were enrolled, and 375 lymph nodes were excised using conventional SLNb. The PAF was used to measure the signal from the excised lymph nodes. We compared the SLN detection rates of each method (gamma probe, visual inspection, and PAF) and conducted a non-inferiority test. The PAF detected 87 % of SLNs, comparable to the gamma probe (85 %) and superior to visual inspection (73 %). Non-inferiority tests confirmed PAF's performance was not inferior to visual inspection (p < 0.001) or the gamma probe (p < 0.015). Using the dual-modal method (gamma probe + visual inspection) as the gold standard, PAF showed a sensitivity of 0.81 and specificity of 0.63. This study demonstrates that PAF, using only blue dye, offers a non-inferior alternative to the standard dual-modal SLN detection method with radioactive materials, opening new avenues for radiation-free SLNb in the future.
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Affiliation(s)
- Moongyu Han
- Department of Convergence IT Engineering, Electrical Engineering, Mechanical Engineering, and Medical Science and Engineering, Medical Device Innovation Center, Pohang University of Science and Technology, 77 Cheongam-ro, Nam-Gu, Pohang 37673, Republic of Korea
| | - Young Joo Lee
- Department of Surgery, Seoul St. Mary's Hospital, College of Medicine, the Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul 06591, Republic of Korea
| | - Junho Ahn
- Department of Convergence IT Engineering, Electrical Engineering, Mechanical Engineering, and Medical Science and Engineering, Medical Device Innovation Center, Pohang University of Science and Technology, 77 Cheongam-ro, Nam-Gu, Pohang 37673, Republic of Korea
| | - Sunghun Nam
- Department of Convergence IT Engineering, Electrical Engineering, Mechanical Engineering, and Medical Science and Engineering, Medical Device Innovation Center, Pohang University of Science and Technology, 77 Cheongam-ro, Nam-Gu, Pohang 37673, Republic of Korea
| | - Minseong Kim
- Department of Convergence IT Engineering, Electrical Engineering, Mechanical Engineering, and Medical Science and Engineering, Medical Device Innovation Center, Pohang University of Science and Technology, 77 Cheongam-ro, Nam-Gu, Pohang 37673, Republic of Korea
| | - Jeongwoo Park
- Department of Biomedical Convergence Science and Technology, Kyungpook National University, Daegu 41566, Republic of Korea
| | - Joongho Ahn
- Department of Convergence IT Engineering, Electrical Engineering, Mechanical Engineering, and Medical Science and Engineering, Medical Device Innovation Center, Pohang University of Science and Technology, 77 Cheongam-ro, Nam-Gu, Pohang 37673, Republic of Korea
| | - Hanyoung Ryu
- R&D Center, WONTECH Co. Ltd., Techno 8-ro, Yuseong-gu, Daejeon 34028, Republic of Korea
| | - Youngseok Seo
- R&D Center, WONTECH Co. Ltd., Techno 8-ro, Yuseong-gu, Daejeon 34028, Republic of Korea
| | - Byullee Park
- Departments of Biophysics, Institute of Quantum Biophysics, Metabiohealth, Biopharmaceutical Convergence, Sungkyunkwan University, Suwon 16419, Republic of Korea
| | - Dooreh Kim
- Department of Surgery, Seoul St. Mary's Hospital, College of Medicine, the Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul 06591, Republic of Korea
| | - Chulhong Kim
- Department of Convergence IT Engineering, Electrical Engineering, Mechanical Engineering, and Medical Science and Engineering, Medical Device Innovation Center, Pohang University of Science and Technology, 77 Cheongam-ro, Nam-Gu, Pohang 37673, Republic of Korea
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Iranian P, Lapauw T, Van den Dries T, Sahakian S, Wuts J, Jacobs VA, Vandemeulebroucke J, Kuijk M, Ingelberts H. Fluorescence Lifetime Endoscopy with a Nanosecond Time-Gated CAPS Camera with IRF-Free Deep Learning Method. SENSORS (BASEL, SWITZERLAND) 2025; 25:450. [PMID: 39860819 PMCID: PMC11768465 DOI: 10.3390/s25020450] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/23/2024] [Revised: 01/10/2025] [Accepted: 01/10/2025] [Indexed: 01/27/2025]
Abstract
Fluorescence imaging has been widely used in fields like (pre)clinical imaging and other domains. With advancements in imaging technology and new fluorescent labels, fluorescence lifetime imaging is gradually gaining recognition. Our research department is developing the tauCAMTM, based on the Current-Assisted Photonic Sampler, to achieve real-time fluorescence lifetime imaging in the NIR (700-900 nm) region. Incorporating fluorescence lifetime into endoscopy could further improve the differentiation of malignant and benign cells based on their distinct lifetimes. In this work, the capabilities of an endoscopic lifetime imaging system are demonstrated using a rigid endoscope involving various phantoms and an IRF-free deep learning-based method with only 6-time points. The results show that this application's fluorescence lifetime image has better lifetime uniformity and precision with 6-time points than the conventional methods.
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Affiliation(s)
- Pooria Iranian
- Department of Electronics and Informatics (ETRO), Vrije Universiteit Brussel, 1050 Brussels, Belgium; (P.I.); (T.L.); (T.V.d.D.); (S.S.); (J.W.); (J.V.); (M.K.)
| | - Thomas Lapauw
- Department of Electronics and Informatics (ETRO), Vrije Universiteit Brussel, 1050 Brussels, Belgium; (P.I.); (T.L.); (T.V.d.D.); (S.S.); (J.W.); (J.V.); (M.K.)
| | - Thomas Van den Dries
- Department of Electronics and Informatics (ETRO), Vrije Universiteit Brussel, 1050 Brussels, Belgium; (P.I.); (T.L.); (T.V.d.D.); (S.S.); (J.W.); (J.V.); (M.K.)
| | - Sevada Sahakian
- Department of Electronics and Informatics (ETRO), Vrije Universiteit Brussel, 1050 Brussels, Belgium; (P.I.); (T.L.); (T.V.d.D.); (S.S.); (J.W.); (J.V.); (M.K.)
| | - Joris Wuts
- Department of Electronics and Informatics (ETRO), Vrije Universiteit Brussel, 1050 Brussels, Belgium; (P.I.); (T.L.); (T.V.d.D.); (S.S.); (J.W.); (J.V.); (M.K.)
| | - Valéry Ann Jacobs
- MOBI Rresearch Center, Vrije Universiteit Brussel, 1050 Brussels, Belgium;
| | - Jef Vandemeulebroucke
- Department of Electronics and Informatics (ETRO), Vrije Universiteit Brussel, 1050 Brussels, Belgium; (P.I.); (T.L.); (T.V.d.D.); (S.S.); (J.W.); (J.V.); (M.K.)
| | - Maarten Kuijk
- Department of Electronics and Informatics (ETRO), Vrije Universiteit Brussel, 1050 Brussels, Belgium; (P.I.); (T.L.); (T.V.d.D.); (S.S.); (J.W.); (J.V.); (M.K.)
| | - Hans Ingelberts
- Department of Electronics and Informatics (ETRO), Vrije Universiteit Brussel, 1050 Brussels, Belgium; (P.I.); (T.L.); (T.V.d.D.); (S.S.); (J.W.); (J.V.); (M.K.)
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Feng C, Jiang X, Feng L, Sun W, Liu Q, Hao Y, Cui B. Comparison of different tracers in sentinel lymph node detection for endometrial cancer: a systematic review and network meta-analysis. Int J Surg 2025; 111:1397-1406. [PMID: 39185991 PMCID: PMC11745743 DOI: 10.1097/js9.0000000000002064] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2024] [Accepted: 08/11/2024] [Indexed: 08/27/2024]
Abstract
BACKGROUND In the realm of endometrial cancer (EC) therapeutics and prognostic assessments, lymph nodes' status is paramount. The sentinel lymph node (SLN) detection, recognized for its reliability, has been progressively adopted as a standard procedure, posing a compelling alternative to conventional systematic lymphadenectomy. However, there remains a lack of agreement on the most effective choice of tracers for this procedure. OBJECTIVE This investigation was dedicated to a comparative analysis of various tracers to identify the most effective combination that achieves the highest detection rate. This endeavor sought to enhance the efficacy of SLN biopsy in the surgical management of EC. METHODS A systematic review was conducted across multiple databases, including the Cochrane Central Register of Controlled Trials, PubMed, Web of Science, Embase, and clinicaltrials.gov, to analyze studies employing different tracers for SLN biopsy during surgery in EC. Using Bayesian network meta-analysis, the authors compared the total and bilateral detection rates of various tracers. RESULTS After screening 1431 articles, 11 studies, including 2699 participants, were selected in this network meta-analysis. The combination of radioactive isotopes and indocyanine green (ICG) emerged as the most efficacious method in total and bilateral detection rates, with the Surface Under the Cumulative Ranking Curve (SUCRA) scores of 80.00 and 86.36%, respectively. Additionally, carbon nanoparticles (CNPs) demonstrated superior performance in the detection of para-aortic lymph nodes with an SUCRA score of 97.77%. CONCLUSION Network meta-analysis shows that the application of radioactive isotopes and ICG is the optimal tracer combination for SLN biopsy during surgery in EC.
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Affiliation(s)
| | | | | | | | | | | | - Baoxia Cui
- Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University, Shandong Province, People’s Republic of China
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Naderi PM, Zargoosh K, Qandalee M, Firuzi O, Behmadi H, Hosseinkhani S, Ghafary SM, Durán-Valle CJ, López-Coca IM. A Fluorescent Furan-based Probe with Protected Functional Groups for Highly Selective and Non-Toxic Imaging of HT-29 Cancer Cells and 4T1 Tumors. Chempluschem 2024; 89:e202400095. [PMID: 38787798 DOI: 10.1002/cplu.202400095] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2024] [Revised: 05/21/2024] [Accepted: 05/24/2024] [Indexed: 05/26/2024]
Abstract
Most of the previously reported fluorescent organic probes for cancer cell and tumor imaging have significant limitations including chemical toxicity, structural instability, low Stokes shift value, and the inability for selective accumulations in tumors during in vivo imaging. To overcome the mentioned challenges, we synthesized the fluorescent probes with protected polar functional groups to enhance the non-toxicity nature and increase the selectivity toward tumors. In addition, the structural rigidity of the fluorescent probes was increased by embedding aromatic rings in the probe structure. This issue enables us to obtain ultrabright cell images due to enhanced fluorescence quantum yield (ΦFL) values. After synthesis and spectral characterizations, the applicability of two furan-based and imidazole-based fluorescent probes ( abbreviated as DCPEF and DBPPI, respectively) was investigated for ultrabright in vitro and in vivo imaging of cancer cells. The probe DCPEF shows the ΦFL value of 0.946 and the Stocks shift of 86 nm. In addition, probe DBPPI offers the ΦFL value of 0.400 and a Stocks shift of 150 nm. The MTT colorimetric cytotoxicity assay showed that probe DCPEF has minimal effects against HT-29 (cancer) and Vero (normal) cells. The probe DCPEF produced ultrabright fluorescence images from HT-29 cells. In addition, in vivo imaging of cancer cells showed that probe DCPEF selectively accumulates in the 4T1 tumor in mice. The spectral and chemical stability, minimal cytotoxicity, significant Stokes shift, and high degree of selectivity for tumor cells during in vivo imaging make DCPEF an appropriate candidate to be used as a standard probe for cancer cell imaging.
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Affiliation(s)
- Parisa Mehdizadeh Naderi
- Department of Chemistry, Isfahan University of Technology, Isfahan, 84156-83111, Islamic Republic of Iran
| | - Kiomars Zargoosh
- Department of Chemistry, Isfahan University of Technology, Isfahan, 84156-83111, Islamic Republic of Iran
| | - Mohammad Qandalee
- Department of Basic Sciences, Garmsar Branch, Islamic Azad University, Garmsar, 3581631167, Islamic Republic of Iran
| | - Omidreza Firuzi
- Medicinal and Natural Products Chemistry Research Center, Shiraz University of Medical Sciences, Shiraz, Islamic Republic of Iran
| | - Hossein Behmadi
- Department of Chemistry, Mashhad Branch, Islamic Azad University, Mashhad, Islamic Republic of Iran
| | - Saman Hosseinkhani
- Department of Biochemistry, Faculty of Biological Science, Tarbiat Modares University, Tehran, Islamic Republic of Iran
| | - Soroush Moasses Ghafary
- Department of Nanobiotechnology, Faculty of Biological Science, Tarbiat Modares University, Tehran, Islamic Republic of Iran
| | - Carlos J Durán-Valle
- IACYS, Department of Organic and Inorganic Chemistry, Faculty of Sciences, Universidad de Extremadura, Badajoz, 06006, Spain
| | - Ignacio M López-Coca
- INTERRA, Department of Organic and Inorganic Chemistry, School of Technology, Universidad de Extremadura, Cáceres - 10003, Spain
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Chu TS, Tzeng YS, Wang CY, Shih YJ, Chen CY, Wang CH. The Utility of Indocyanine Green Dye Fluorescence Lymphography and Angiography During Wide Excision of Cutaneous Melanoma. Surg Innov 2022; 29:566-572. [PMID: 34555944 DOI: 10.1177/15533506211020226] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
Background and Objectives. Lymph node status is the most important prognostic factor in cutaneous melanoma patients. Recent studies showed that indocyanine green (ICG) fluorescence lymphography helps locating sentinel nodes better. Sometimes, flap reconstruction is needed after wide excision of tumor. Indocyanine green fluorescence also simplifies the intraoperative design of flaps. This study investigates the use of ICG fluorescence in patients with cutaneous melanoma during operation. Methods. We performed a single-center, retrospective study of subjects with cutaneous melanoma using ICG lymphograhy and/or angiography during wide excision of tumor between 2015 and 2019. Patients received a dermal injection of ICG and patent blue (PB) dye. The positive node was excised. Indocyanine green angiography was utilized to visualize better skin paddle during flap reconstruction if needed. Results. A total of 37 sentinel lymph nodes (SLNs) were removed in 12 patients. Indocyanine green successful localization was found in 10 of the 12 patients (83%). Three patients were found with 6 metastatic nodes on final pathology. 100% of these 6 nodes were identified by ICG, while 83% (5/6) were positive PB. Three of the 12 patients received flap reconstruction after operation, and no major complications occurred. Conclusions. ICG dye lymphangiography is a good alternative for locating SLNs in patients with melanoma. It could also visualize well perfusion skin paddle during reconstruction. We reported a reproducible and simple method to utilize ICG fluorescence in cutaneous melanoma patients.
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Affiliation(s)
- Tzi-Shiang Chu
- Division of Plastic Surgery, Department of Surgery, 63452Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
- Department of Surgery, Taichung Armed Forces General Hospital, Taichung, Taiwan
| | - Yuan-Sheng Tzeng
- Division of Plastic Surgery, Department of Surgery, 63452Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
| | - Chi-Yu Wang
- Division of Plastic Surgery, Department of Surgery, 63452Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
| | - Yu-Jen Shih
- Division of Plastic Surgery, Department of Surgery, 63452Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
| | - Chun-Yu Chen
- Division of Plastic Surgery, Department of Surgery, 63452Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
| | - Chih-Hsin Wang
- Division of Plastic Surgery, Department of Surgery, 63452Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
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Baeten IGT, Hoogendam JP, Braat AJAT, Veldhuis WB, Jonges GN, Jürgenliemk-Schulz IM, Zweemer RP, Gerestein CG. Fluorescent Indocyanine Green versus Technetium-99m and Blue Dye for Bilateral SENTinel Lymph Node Detection in Stage I-IIA Cervical Cancer (FluoreSENT): protocol for a non-inferiority study. BMJ Open 2022; 12:e061829. [PMID: 36100304 PMCID: PMC9472172 DOI: 10.1136/bmjopen-2022-061829] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/30/2022] Open
Abstract
INTRODUCTION Nowadays, two predominant methods for detecting sentinel lymph nodes (SLNs) in cervical cancer are in use. The most conventional method is a combination of a radiotracer, technetium-99m (99mTc) and blue dye. More recently, another method for SLN mapping using indocyanine green (ICG) is becoming widely accepted. ICG is a fluorescent dye, visualised intraoperatively with near-infrared (NIR) fluorescence imaging, providing real-time visual navigation. The presumed advantages of ICG over 99mTc, that is, being cheaper, non-radioactive and logistically more attractive, are only valuable if its detection rate proves to be at least non-inferior. Before omitting the well-functioning and evidence-based combined approach of 99mTc and blue dye, we aim to provide prospective evidence on the non-inferiority of ICG with NIR fluorescence imaging. METHODS AND ANALYSIS We initiated a prospective non-inferiority study with a paired comparison of both SLN methods in a single sample of 101 patients with International Federation of Gynecology and Obstetrics (FIGO) stage IA-IB2 or IIA1 cervical cancer receiving primary surgical treatment. All patients undergo SLN mapping with ICG and NIR fluorescence imaging in adjunct to mapping with 99mTc (including single photon emission computed tomography with X-ray computed tomography (SPECT/CT)) and blue dye. Surgeons start SLN detection with ICG while being blinded for the preoperative outcome of SPECT/CT to avoid biased detection with ICG. Primary endpoint of this study is bilateral SLN detection rate of both methods (ie, detection of at least one SLN in each hemipelvis). Since we compare strategies for SLN mapping that are already applied in current daily practice for different types of cancer, no additional risks or burdens are expected from these study procedures. ETHICS AND DISSEMINATION The current study is approved by the Medical Ethics Research Committee Utrecht (reference number 21-014). Findings arising from this study will be disseminated in peer-reviewed journals, academic conferences and through patient organisations. TRIAL REGISTRATION NUMBER NL9011 and EudraCT 2020-005134-15.
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Affiliation(s)
- Ilse G T Baeten
- Department of Gynaecologic Oncology, Division of Imaging and Oncology, University Medical Center Utrecht, Utrecht, Netherlands
| | - Jacob P Hoogendam
- Department of Gynaecologic Oncology, Division of Imaging and Oncology, University Medical Center Utrecht, Utrecht, Netherlands
| | - Arthur J A T Braat
- Department of Radiology and Nuclear Medicine, Division of Imaging and Oncology, University Medical Center Utrecht, Utrecht, Netherlands
| | - Wouter B Veldhuis
- Department of Radiology and Nuclear Medicine, Division of Imaging and Oncology, University Medical Center Utrecht, Utrecht, Netherlands
| | - Geertruida N Jonges
- Department of Pathology, Division of Laboratory, Pharmacy and Biomedical Genetics, University Medical Center Utrecht, Utrecht, Netherlands
| | - Ina M Jürgenliemk-Schulz
- Department of Radiotherapy, Division of Imaging and Oncology, University Medical Center Utrecht, Utrecht, Netherlands
| | - Ronald P Zweemer
- Department of Gynaecologic Oncology, Division of Imaging and Oncology, University Medical Center Utrecht, Utrecht, Netherlands
| | - Cornelis G Gerestein
- Department of Gynaecologic Oncology, Division of Imaging and Oncology, University Medical Center Utrecht, Utrecht, Netherlands
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Highly bright aggregation-induced emission nanodots for precise photoacoustic/NIR-II fluorescence imaging-guided resection of neuroendocrine neoplasms and sentinel lymph nodes. Biomaterials 2022; 289:121780. [DOI: 10.1016/j.biomaterials.2022.121780] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2022] [Revised: 07/11/2022] [Accepted: 07/27/2022] [Indexed: 11/18/2022]
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Zhang GM, Jiao D, Nie SC, Xu ZY, Zhang X, Dai Y, Jiao MN, Ou H, Yan YB, Ding D. Near-infrared aggregation-induced emission nanodots for early diagnosis of tongue squamous cell carcinoma and sentinel lymph nodes mapping. Biomater Sci 2022; 10:1929-1935. [PMID: 35253811 DOI: 10.1039/d1bm01976g] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
Fluorescence imaging has been widely used in the biomedical field owing to its merits of high sensitivity, superb accuracy, high biosafety, etc. However, despite the well performance of fluorescent materials...
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Affiliation(s)
- Guan-Meng Zhang
- Department of Oromaxillofacial-Head and Neck Surgery, Tianjin Stomatological Hospital, and Hospital of Stomatology, Nankai University, Tianjin 300041, China.
| | - Di Jiao
- State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Bioactive Materials, Ministry of Education, and College of Life Sciences, Nankai University, Tianjin 300071, China.
| | | | - Zhao-Yuan Xu
- Department of Oromaxillofacial-Head and Neck Surgery, Tianjin Stomatological Hospital, and Hospital of Stomatology, Nankai University, Tianjin 300041, China.
| | - Xiaoyan Zhang
- Department of Oromaxillofacial-Head and Neck Surgery, Tianjin Stomatological Hospital, and Hospital of Stomatology, Nankai University, Tianjin 300041, China.
| | - Yanmei Dai
- Department of Oromaxillofacial-Head and Neck Surgery, Tianjin Stomatological Hospital, and Hospital of Stomatology, Nankai University, Tianjin 300041, China.
- Tianjin Key Laboratory of Oral and Maxillofacial Function Reconstruction, Tianjin Stomatological Hospital, and Hospital of Stomatology, Nankai University, Tianjin 300041, China
| | | | - Hanlin Ou
- State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Bioactive Materials, Ministry of Education, and College of Life Sciences, Nankai University, Tianjin 300071, China.
| | - Ying-Bin Yan
- Department of Oromaxillofacial-Head and Neck Surgery, Tianjin Stomatological Hospital, and Hospital of Stomatology, Nankai University, Tianjin 300041, China.
- Tianjin Key Laboratory of Oral and Maxillofacial Function Reconstruction, Tianjin Stomatological Hospital, and Hospital of Stomatology, Nankai University, Tianjin 300041, China
| | - Dan Ding
- Department of Oromaxillofacial-Head and Neck Surgery, Tianjin Stomatological Hospital, and Hospital of Stomatology, Nankai University, Tianjin 300041, China.
- State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Bioactive Materials, Ministry of Education, and College of Life Sciences, Nankai University, Tianjin 300071, China.
- Tianjin Key Laboratory of Oral and Maxillofacial Function Reconstruction, Tianjin Stomatological Hospital, and Hospital of Stomatology, Nankai University, Tianjin 300041, China
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Sánchez-Izquierdo N, Vidal-Sicart S, Campos F, Torné A, Angeles MA, Migliorelli F, Munmany M, Saco A, Diaz-Feijoo B, Glickman A, Ordi J, Perissinotti A, del Pino M, Paredes P. Detection of the sentinel lymph node with hybrid tracer (ICG-[ 99mTc]Tc-albumin nanocolloid) in intermediate- and high-risk endometrial cancer: a feasibility study. EJNMMI Res 2021; 11:123. [PMID: 34905122 PMCID: PMC8671586 DOI: 10.1186/s13550-021-00863-x] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2021] [Accepted: 11/17/2021] [Indexed: 11/10/2022] Open
Abstract
PURPOSE Indocyanine green (ICG) is frequently used for the detection of the sentinel lymph node (SLN) in gynecology, but it carries the loss of the presurgical SLN mapping provided by [99mTc]-based colloids. Hybrid tracers such as ICG-[99mTc]Tc-albumin nanocolloid combine the benefits of both components. The aim of this study was to evaluate the feasibility and applicability of this hybrid tracer injected by transvaginal ultrasound-guided myometrial injection of radiotracer (TUMIR) approach in the detection of SLNs in patients with intermediate- and high-risk EC. METHODS Fifty-two patients with intermediate- and high-risk EC underwent SLN biopsy after injection of a hybrid tracer using the TUMIR approach, followed by pelvic and paraaortic lymphadenectomy. SLNs were detected preoperatively by lymphoscintigraphic study and intraoperatively by gamma probe and near-infrared (NIR) optical laparoscopic camera. RESULTS Preoperative lymphatic drainage was obtained in 69% and intraoperative detection in 71.4% of patients. A total of 146 SLNs (4.17 SLNs/patient) were biopsied. Pelvic bilateral detection was observed in 57% of the women and paraaortic drainage in 34% of the patients. The radioactive component allowed the detection of SLN in 97.1% of the patients, while the fluorescent component detected 80%. In more than 17% of the patients with intraoperative detection, SLNs were detected only by the radioactive signal. Lymph node metastasis was identified in 14.3% of patients submitted to SLNB. The sensitivity and negative predictive value for metastatic involvement were 100%. CONCLUSION TUMIR injection of a hybrid tracer in patients with intermediate- and high-risk EC combines the benefits of the radiotracer and the fluorescence methods with a single tracer. The method increases the paraaortic detection rate and allows a potential increase in SLN detection. Notwithstanding, based on our findings, the radioactive component of the hybrid tracer cannot be obviated.
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Affiliation(s)
- Nuria Sánchez-Izquierdo
- Department of Nuclear Medicine, Hospital Clínic of Barcelona, Villarroel 170, 08036 Barcelona, Spain
| | - Sergi Vidal-Sicart
- Department of Nuclear Medicine, Hospital Clínic of Barcelona, Villarroel 170, 08036 Barcelona, Spain
- Institut d’Investigacions Biomèdiques August Pi I Sunyer (IDIBAPS), Barcelona, Spain
| | - Francisco Campos
- Department of Nuclear Medicine, Hospital Clínic of Barcelona, Villarroel 170, 08036 Barcelona, Spain
| | - Aureli Torné
- Institute Clinic of Gynecology, Obstetrics, and Neonatology, Hospital Clínic of Barcelona, Barcelona, Spain
- Institut d’Investigacions Biomèdiques August Pi I Sunyer (IDIBAPS), Barcelona, Spain
- Faculty of Medicine, University of Barcelona, Barcelona, Spain
| | - Martina Aida Angeles
- Institute Clinic of Gynecology, Obstetrics, and Neonatology, Hospital Clínic of Barcelona, Barcelona, Spain
- Department of Surgical Oncology, Institut Claudius Regaud, Institut Universitaire du Cancer de Toulouse - Oncopole, Toulouse, France
| | - Federico Migliorelli
- Department of Gynecology and Obstetrics, Centre Hospitalier Intercommunal des Vallées de l’Ariège, Saint-Jean-de-Verges, France
| | - Meritxell Munmany
- Institute Clinic of Gynecology, Obstetrics, and Neonatology, Hospital Clínic of Barcelona, Barcelona, Spain
| | - Adela Saco
- Department of Pathology, Hospital Clínic of Barcelona, Barcelona, Spain
- Institut d’Investigacions Biomèdiques August Pi I Sunyer (IDIBAPS), Barcelona, Spain
- Faculty of Medicine, University of Barcelona, Barcelona, Spain
| | - Berta Diaz-Feijoo
- Institute Clinic of Gynecology, Obstetrics, and Neonatology, Hospital Clínic of Barcelona, Barcelona, Spain
- Institut d’Investigacions Biomèdiques August Pi I Sunyer (IDIBAPS), Barcelona, Spain
- Faculty of Medicine, University of Barcelona, Barcelona, Spain
| | - Ariel Glickman
- Institute Clinic of Gynecology, Obstetrics, and Neonatology, Hospital Clínic of Barcelona, Barcelona, Spain
| | - Jaume Ordi
- Department of Pathology, Hospital Clínic of Barcelona, Barcelona, Spain
- Faculty of Medicine, University of Barcelona, Barcelona, Spain
- ISGlobal, Barcelona Institute for Global Health, Hospital Clínic-Universitat de Barcelona, 08036 Barcelona, Spain
| | - Andrés Perissinotti
- Department of Nuclear Medicine, Hospital Clínic of Barcelona, Villarroel 170, 08036 Barcelona, Spain
| | - Marta del Pino
- Institute Clinic of Gynecology, Obstetrics, and Neonatology, Hospital Clínic of Barcelona, Barcelona, Spain
- Institut d’Investigacions Biomèdiques August Pi I Sunyer (IDIBAPS), Barcelona, Spain
- Faculty of Medicine, University of Barcelona, Barcelona, Spain
| | - Pilar Paredes
- Department of Nuclear Medicine, Hospital Clínic of Barcelona, Villarroel 170, 08036 Barcelona, Spain
- Institut d’Investigacions Biomèdiques August Pi I Sunyer (IDIBAPS), Barcelona, Spain
- Faculty of Medicine, University of Barcelona, Barcelona, Spain
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10
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Multi-Aspect Optoacoustic Imaging of Breast Tumors under Chemotherapy with Exogenous and Endogenous Contrasts: Focus on Apoptosis and Hypoxia. Biomedicines 2021; 9:biomedicines9111696. [PMID: 34829925 PMCID: PMC8615838 DOI: 10.3390/biomedicines9111696] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2021] [Revised: 10/29/2021] [Accepted: 11/08/2021] [Indexed: 12/01/2022] Open
Abstract
Breast cancer is a complex tumor type involving many biological processes. Most chemotherapeutic agents exert their antitumoral effects by rapid induction of apoptosis. Another main feature of breast cancer is hypoxia, which may drive malignant progression and confer resistance to various forms of therapy. Thus, multi-aspect imaging of both tumor apoptosis and oxygenation in vivo would be of enormous value for the effective evaluation of therapy response. Herein, we demonstrate the capability of a hybrid imaging modality known as multispectral optoacoustic tomography (MSOT) to provide high-resolution, simultaneous imaging of tumor apoptosis and oxygenation, based on both the exogenous contrast of an apoptosis-targeting dye and the endogenous contrast of hemoglobin. MSOT imaging was applied on mice bearing orthotopic 4T1 breast tumors before and following treatment with doxorubicin. Apoptosis was monitored over time by imaging the distribution of xPLORE-APOFL750©, a highly sensitive poly-caspase binding apoptotic probe, within the tumors. Oxygenation was monitored by tracking the distribution of oxy- and deoxygenated hemoglobin within the same tumor areas. Doxorubicin treatment induced an increase in apoptosis-depending optoacoustic signal of xPLORE-APOFL750© at 24 h after treatment. Furthermore, our results showed spatial correspondence between xPLORE-APO750© and deoxygenated hemoglobin. In vivo apoptotic status of the tumor tissue was independently verified by ex vivo fluorescence analysis. Overall, our results provide a rationale for the use of MSOT as an effective tool for simultaneously investigating various aspects of tumor pathophysiology and potential effects of therapeutic regimes based on both endogenous and exogenous molecular contrasts.
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11
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Borčinová M, Ragosch V, Jarkovský J, Bajsová S, Pilka R, Glickman A, Garrido-Mallach S, Raspagliesi F, Szatkowski W, Pakiz M, Snyman LC, Kocián R, Tamussino K, Kalist V, Michal M, Segovia MG, Poka R, Kipp B, Szewczyk G, Wydra D, Tóth R, Vinnytska A, Fischerová D, Siegler K, Cibula D. Challenges in lower limb lymphoedema assessment based on limb volume change: Lessons learnt from the SENTIX prospective multicentre study. Gynecol Oncol 2021; 164:76-84. [PMID: 34763939 DOI: 10.1016/j.ygyno.2021.10.089] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2021] [Revised: 10/18/2021] [Accepted: 10/20/2021] [Indexed: 11/20/2022]
Abstract
BACKGROUND Lower limb lymphoedema (LLL) is the most disabling adverse effect of surgical staging of pelvic lymph nodes. However, the lack of standardisation of volumetric LLL assessment hinders direct comparison between the studies and makes LLL reporting unreliable. The aim of our study is to report outcomes from a prospective trial that have implications for LLL assessment standardisation. METHODS In the prospective international multicentre trial SENTIX, a group of 150 patients with stage IA1-IB2 cervical cancer treated by uterine surgery with bilateral sentinel lymph node biopsy was prospectively evaluated by objective LLL assessment, based on limb volume change (LVC) using circumferrential limb measurements and subjective patient-reported swelling. The assessments were conducted in six-month periods over 24 months post-surgery. RESULTS Patient LVC substantially fluctuated in both positive and negative directions, which were comparable in frequency up to ±14% change. Thirty-eight patients experienced persistent LVC increase >10% classified as LLL, with nine months median time to onset. Some 34.2% of cases experienced onset later than one year after the surgery. Thirty-three patients (22%) experienced transient oedema characterised as LVC >10%, which resolved without intervention between two consequent follow-up visits. No significant correlation between LVC >10% and a patient-reported swelling was observed. CONCLUSIONS Given that we observed comparable fluctuations of the the lower-limb volumes after surgical treatment of cervical cancer in both positive and negative direction up to ±14%, the diagnostic threshold for LLL diagnosis based on LVC should be increased to >15% LVC. The distinction of transient oedema from persistent LLL requires repeated measurements. Also, as one-third of LLL cases are diagnosed >1-year post-surgery, a sufficient follow-up duration needs to be ensured. Patient-reported swelling correlated poorly with LVC and should only be used as an adjunct to objective LLL assessment. TRIAL REGISTRATION ClinicalTrials.gov: NCT02494063.
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Affiliation(s)
- Martina Borčinová
- Gynecologic Oncology Centre, Department of Obstetrics and Gynaecology, First Faculty of Medicine, Charles University and General University Hospital, Central and Eastern European Gynecologic Oncology Group, CEEGOG, Prague, Czech Republic
| | - Volker Ragosch
- Department of Special Operative and Oncologic Gynaecology, Asklepios-Clinic Hamburg, Hamburg, Germany
| | - Jiří Jarkovský
- Institute of Biostatistics and Analyses, Faculty of Medicine, Masaryk University, Brno, Czech Republic
| | - Sylva Bajsová
- Department of Obstetrics and Gynecology, University Hospital Ostrava, Central and Eastern European Gynecologic Oncology Group, CEEGOG, Ostrava Poruba, Czech Republic
| | - Radovan Pilka
- Department of Obstetrics and Gynecology, Faculty of Medicine and Dentistry, Palacky University, University Hospital Olomouc, Central and Eastern European Gynecologic Oncology Group, CEEGOG, Olomouc, Czech Republic
| | - Ariel Glickman
- Unit of Gynecological Oncology, Institute Clinic of Gynaecology, Obstetrics, and Neonatology, Hospital Clinic-Institut d'Investigacions Biomediques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain
| | | | | | | | - Maja Pakiz
- University medical Centre Maribor, Slovenia
| | | | - Roman Kocián
- Gynecologic Oncology Centre, Department of Obstetrics and Gynaecology, First Faculty of Medicine, Charles University and General University Hospital, Central and Eastern European Gynecologic Oncology Group, CEEGOG, Prague, Czech Republic
| | | | | | | | | | - Robert Poka
- Department of obstetrics and Gynecology, University of Debrecen, Hungary
| | - Barbara Kipp
- Neue Freuenklinik, Luzerner Kantonsspital, Switzerland
| | | | | | - Róbert Tóth
- Oncology Institute of East Slovakia, Košice, Slovakia
| | | | - Daniela Fischerová
- Gynecologic Oncology Centre, Department of Obstetrics and Gynaecology, First Faculty of Medicine, Charles University and General University Hospital, Central and Eastern European Gynecologic Oncology Group, CEEGOG, Prague, Czech Republic
| | - Kathrin Siegler
- Department of Special Operative and Oncologic Gynaecology, Asklepios-Clinic Hamburg, Hamburg, Germany
| | - David Cibula
- Gynecologic Oncology Centre, Department of Obstetrics and Gynaecology, First Faculty of Medicine, Charles University and General University Hospital, Central and Eastern European Gynecologic Oncology Group, CEEGOG, Prague, Czech Republic.
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Sentinel Lymph Node Staging with Indocyanine Green for Patients with Cervical Cancer: The Safety and Feasibility of Open Approach Using SPY-PHI Technique. J Clin Med 2021; 10:jcm10214849. [PMID: 34768367 PMCID: PMC8584791 DOI: 10.3390/jcm10214849] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2021] [Revised: 10/16/2021] [Accepted: 10/20/2021] [Indexed: 11/25/2022] Open
Abstract
Simple Summary While several studies have been conducted on the safety and efficacy of sentinel lymph node technique during minimally invasive radical hysterectomy and indicated that using indocyanine green alone is a better tracer agent, there is now high unmet medical need and growing demand for more data about sentinel lymph node detection and the most suitable tracer in open surgery for cervical cancer, especially after the publishing of the of Laparoscopic Approach to Cervical Cancer (LACC) Trial data. The aim of this study is to assess the feasibility and safety of sentinel lymph nodes with indocyanine green in cervical cancer patients undergoing radical hysterectomy in open surgery and to compare the detection rates of this tracer in the open versus laparoscopic approaches. Abstract (1) Background: Sentinel lymph node staging (SLN) with indocyanine green (ICG) in cervical cancer is the standard of care in most national and international guidelines. However, the vast majority of relevant studies about the safety and feasibility of this method are conducted on minimally invasive surgery; (2) Methods: This study is a retrospective analysis of a retrospective collected database of 76 consecutive patients with cervical cancers, who were operated laparoscopically (50%), or laparotomy (50%). Sentinel nodes were defined as the ICG-positive pelvic nodes in the first and second echelons. False negative cases were defined as positive non-sentinel lymph nodes despite successful sentinel mapping or failed mapping bilaterally by per-patient assessment or unilaterally by pelvic sidewall assessment; (3) Results: Regardless of the approach (open or laparoscopic), the SLN technique achieved a total sensitivity, specificity, and negative predictive value (NPV) of 94.7%, 98.6%, and 94.7%, respectively in the entire sample. The bilateral detection rate was as high as 93.4% with identical results in both approaches. The sensitivity and NPV for SNL in open surgery was found to be similar to minimal access surgery; (4) Conclusions: ICG and SPY-PHI technique is a reliable tool to detect sentinel lymph nodes in cervical cancer during laparotomy.
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13
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Comprehensive Review of Fluorescence Applications in Gynecology. J Clin Med 2021; 10:jcm10194387. [PMID: 34640405 PMCID: PMC8509149 DOI: 10.3390/jcm10194387] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2021] [Revised: 09/22/2021] [Accepted: 09/22/2021] [Indexed: 12/11/2022] Open
Abstract
Since the introduction of indocyanine green (ICG) as a fluorophore in near-infrared imaging, fluorescence visualization has become an essential tool in many fields of surgery. In the field of gynecology, recent new applications have been proposed and found their place in clinical practice. Different applications in gynecology were investigated, subcategorized, and overviewed concerning surgical applications and available dyes. Specific applications in which fluorescence-guided surgery was implemented in gynecology are described in this manuscript—namely, sentinel node biopsy, mesometrium visualization, angiography of different organs, safety issues in pregnant women, ureters visualization, detection of peritoneal metastases, targeted fluorophores for cancer detection, fluorescent contamination hysterectomy, lymphography for lower limb lymphedema prevention, tumor margin detection, endometriosis, and metastases mapping. With evolving technology, further innovative research on the new applications of fluorescence visualization in cancer surgery may help to establish these techniques as standards of high-quality surgery in gynecology. However, more investigations are necessary in order to assess if these innovative tools can also be effective to improve patient outcomes and quality of life in different gynecologic malignancies.
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Sievert M, Mantsopoulos K, Iro H, Koch M. [Near-infrared sentinel diagnostics in head and neck squamous cell carcinoma: a systematic review]. Laryngorhinootologie 2021; 101:383-389. [PMID: 34049415 DOI: 10.1055/a-1507-5492] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
Abstract
BACKGROUND Near-infrared fluorescence (NIR) imaging is a new technique for intraoperative identification of sentinel lymph nodes (SLN). It has shown promising results in several surgical specialties. This article reviews the current study situation of NIR SLN diagnosis of head and neck malignancy. MATERIAL AND METHODS systematic literature search in the following online databases: PubMed, MEDLINE, Thompson Reuters Web of Science, SPIE for the search terms: sentinel node, sentinel node biopsy, head and neck squamous cell carcinoma, near-infrared imaging, indocyanine green, icg. Evaluation of scientific relevance of papers according to established criteria. RESULTS Studies were analyzed in terms of clinical application, clinical reporting, identification rate, and false-negative rate. The identification rate of SLN is 97-100 %, with an average of 1.2-3.4 fluorescence positive lymph nodes per examination. The overall false-negative rate varies between 0 and 20 %. CONCLUSIONS In the synopsis of the currently published results, NIR imaging promises the great potential to improve the diagnosis of SLN in carcinomas of the oral cavity and pharynx. A simple and fast procedure with high spatial resolution and without radiation exposure is beneficial.
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Affiliation(s)
- Matti Sievert
- Hals-Nasen-Ohrenklinik, Kopf- und Hals-Chirurgie, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Deutschland
| | - Konstantinos Mantsopoulos
- Hals-Nasen-Ohrenklinik, Kopf- und Hals-Chirurgie, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Deutschland
| | - Heinrich Iro
- Hals-Nasen-Ohrenklinik, Kopf- und Hals-Chirurgie, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Deutschland
| | - Michael Koch
- Hals-Nasen-Ohrenklinik, Kopf- und Hals-Chirurgie, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Deutschland
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15
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Recent Developments of ICG-Guided Sentinel Lymph Node Mapping in Oral Cancer. Diagnostics (Basel) 2021; 11:diagnostics11050891. [PMID: 34067713 PMCID: PMC8156251 DOI: 10.3390/diagnostics11050891] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2021] [Revised: 05/08/2021] [Accepted: 05/11/2021] [Indexed: 12/13/2022] Open
Abstract
Sentinel lymph node (SLN) biopsy has gained attention as a method of minimizing the extent of neck dissection with a similar survival rate as elective neck dissection in oral cancer. Indocyanine green (ICG) imaging is widely used in the field of surgical oncology. Real-time ICG-guided SLN imaging has been widely used in minimally invasive surgeries for various types of cancers. Here, we provide an overview of conventional SLN biopsy and ICG-guided SLN mapping techniques for oral cancer. Although ICG has many strengths, it still has limitations regarding its potential use as an ideal compound for SLN mapping. The development of novel fluorophores and imaging technology is needed for accurate identification of SLNs, which will allow precision surgery that would reduce morbidities and increase patient survival.
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16
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Bizzarri N, Luigi PA, Ferrandina G, Zannoni GF, Carbone MV, Fedele C, Teodorico E, Gallotta V, Gueli Alletti S, Chiantera V, Fagotti A, Scambia G, Fanfani F. Sentinel lymph node mapping with indocyanine green in cervical cancer patients undergoing open radical hysterectomy: a single-institution series. J Cancer Res Clin Oncol 2021; 147:649-659. [PMID: 33000339 PMCID: PMC7873085 DOI: 10.1007/s00432-020-03393-6] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2020] [Accepted: 09/10/2020] [Indexed: 11/25/2022]
Abstract
PURPOSE To assess the rate of bilateral sentinel lymph node (SLN) detection with indocyanine green (ICG), to evaluate the sensitivity and the negative predictive value of cervical cancer patients undergoing open radical hysterectomy; to compare open versus minimally invasive SLN biopsy performance and to assess factors related to no/unilateral SLN mapping. METHODS We retrospectively reviewed consecutive patients with FIGO 2018 stage IA1 with lymph-vascular space involvement to IIB and IIIC1p cervical carcinoma who underwent SLN mapping with ICG followed by systematic pelvic lymphadenectomy between 05/2017 and 06/2020. Patients were divided according to surgical approach for statistical analysis. RESULTS Eighty-five patients met inclusion criteria. Twenty-seven (31.8%) underwent open and 58 (68.2%) underwent minimally invasive SLN mapping. No difference in any SLN mapping (laparotomy 92.6% and minimally invasive 91.4%) or in SLN bilateral detection (laparotomy 72.0% and minimally invasive 84.9%) (p = 0.850 and p = 0.222, respectively), in median number of SLNs mapped and retrieved (2 in both groups, p = 0.165) and in site of SLN mapping per hemi-pelvis (right side, p = 0273 and left side, p = 0.618) was evident between open and minimally invasive approach. Per-patient sensitivity of SLN biopsy in laparotomy was 83.3% (95% CI 35.9-99.6%) and the negative predictive value was 95.0% (95% CI 76.0-99.1%). No difference in per-patient sensitivity was noted between two approaches (p = 0.300). None of the analyzed variables was associated with no/unilateral SLN mapping. CONCLUSION The use of ICG to detect SLN in cervical cancer treated with open surgery allows a bilateral detection, sensitivity and negative predictive value comparable to minimally invasive surgery with potential advantages of ICG compared to other tracers.
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Affiliation(s)
- Nicolò Bizzarri
- UOC Ginecologia Oncologica, Dipartimento per la salute della Donna e del Bambino e della Salute Pubblica, Fondazione Policlinico Universitario A. Gemelli, IRCCS, Largo Agostino Gemelli 8, 00168, Rome, Italy
| | - Pedone Anchora Luigi
- UOC Ginecologia Oncologica, Dipartimento per la salute della Donna e del Bambino e della Salute Pubblica, Fondazione Policlinico Universitario A. Gemelli, IRCCS, Largo Agostino Gemelli 8, 00168, Rome, Italy
| | - Gabriella Ferrandina
- UOC Ginecologia Oncologica, Dipartimento per la salute della Donna e del Bambino e della Salute Pubblica, Fondazione Policlinico Universitario A. Gemelli, IRCCS, Largo Agostino Gemelli 8, 00168, Rome, Italy
- Università Cattolica del Sacro Cuore, Largo Francesco Vito 1, 00168, Rome, Italy
| | - Gian Franco Zannoni
- Università Cattolica del Sacro Cuore, Largo Francesco Vito 1, 00168, Rome, Italy
- Unità di Gineco-Patologia e Patologia Mammaria, Dipartimento per la salute della Donna e del Bambino e della Salute Pubblica, Fondazione Policlinico Universitario A. Gemelli, IRCCS, Largo Agostino Gemelli 8, 00168, Rome, Italy
| | - Maria Vittoria Carbone
- UOC Ginecologia Oncologica, Dipartimento per la salute della Donna e del Bambino e della Salute Pubblica, Fondazione Policlinico Universitario A. Gemelli, IRCCS, Largo Agostino Gemelli 8, 00168, Rome, Italy
| | - Camilla Fedele
- UOC Ginecologia Oncologica, Dipartimento per la salute della Donna e del Bambino e della Salute Pubblica, Fondazione Policlinico Universitario A. Gemelli, IRCCS, Largo Agostino Gemelli 8, 00168, Rome, Italy
| | - Elena Teodorico
- UOC Ginecologia Oncologica, Dipartimento per la salute della Donna e del Bambino e della Salute Pubblica, Fondazione Policlinico Universitario A. Gemelli, IRCCS, Largo Agostino Gemelli 8, 00168, Rome, Italy
| | - Valerio Gallotta
- UOC Ginecologia Oncologica, Dipartimento per la salute della Donna e del Bambino e della Salute Pubblica, Fondazione Policlinico Universitario A. Gemelli, IRCCS, Largo Agostino Gemelli 8, 00168, Rome, Italy
| | - Salvatore Gueli Alletti
- UOC Ginecologia Oncologica, Dipartimento per la salute della Donna e del Bambino e della Salute Pubblica, Fondazione Policlinico Universitario A. Gemelli, IRCCS, Largo Agostino Gemelli 8, 00168, Rome, Italy
| | - Vito Chiantera
- Department of Gynecologic Oncology, ARNAS Ospedali Civico di Cristina Benfratelli, University of Palermo, Piazza Nicola Leotta 4/A, 90127, Palermo, Italy
| | - Anna Fagotti
- UOC Ginecologia Oncologica, Dipartimento per la salute della Donna e del Bambino e della Salute Pubblica, Fondazione Policlinico Universitario A. Gemelli, IRCCS, Largo Agostino Gemelli 8, 00168, Rome, Italy
- Università Cattolica del Sacro Cuore, Largo Francesco Vito 1, 00168, Rome, Italy
| | - Giovanni Scambia
- UOC Ginecologia Oncologica, Dipartimento per la salute della Donna e del Bambino e della Salute Pubblica, Fondazione Policlinico Universitario A. Gemelli, IRCCS, Largo Agostino Gemelli 8, 00168, Rome, Italy.
- Università Cattolica del Sacro Cuore, Largo Francesco Vito 1, 00168, Rome, Italy.
| | - Francesco Fanfani
- UOC Ginecologia Oncologica, Dipartimento per la salute della Donna e del Bambino e della Salute Pubblica, Fondazione Policlinico Universitario A. Gemelli, IRCCS, Largo Agostino Gemelli 8, 00168, Rome, Italy
- Università Cattolica del Sacro Cuore, Largo Francesco Vito 1, 00168, Rome, Italy
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Liu S, Li Y, Zhang J, Zhang H, Wang Y, Chuah C, Tang Y, Lam J, Kwok R, Ou H, Ding D, Tang B. A two-in-one Janus NIR-II AIEgen with balanced absorption and emission for image-guided precision surgery. Mater Today Bio 2021; 10:100087. [PMID: 33889836 PMCID: PMC8050777 DOI: 10.1016/j.mtbio.2020.100087] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2020] [Revised: 11/23/2020] [Accepted: 11/25/2020] [Indexed: 02/07/2023] Open
Abstract
Fluorescence imaging in the near-infrared II (NIR-II, 1000-1700 nm) region opens up new avenues for biological systems due to suppressed scattering and low autofluorescence at longer-wavelength photons. Nonetheless, the development of organic NIR-II fluorophores is still limited mainly due to the shortage of efficient molecular design strategy. Herein, we propose an approach of designing Janus NIR-II fluorophores by introducing electronic donors with distinct properties into one molecule. As a proof-of-concept, fluorescent dye 2 TT-m, oC6B with both twisted and planar electronic donors displayed balanced absorption and emission which were absent in its parent compound. The key design strategy for Janus molecule is that it combines the merits of intense absorption from planar architecture and high fluorescence quantum yield from twisted motif. The resulting 2 TT-m, oC6B nanoparticles exhibit a high molar absorptivity of 1.12 ⨯104 M-1 cm-1 at 808 nm and a NIR-II quantum yield of 3.7%, displaying a typical aggregation-induced emission (AIE) attribute. The highly bright and stable 2 TT-m, oC6B nanoparticles assured NIR-II image-guided cancer surgery to resect submillimeter tumor nodules. The present study may inspire further development of molecular design philosophy for highly bright NIR-II fluorophores for biomedical applications.
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Affiliation(s)
- S. Liu
- Department of Chemistry, Hong Kong Branch of Chinese National Engineering Research Center for Tissue Restoration and Reconstruction, Division of Life Science and State Key Laboratory of Molecular Neuroscience, Division of Biomedical Engineering, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China
| | - Y. Li
- Department of Chemistry, Hong Kong Branch of Chinese National Engineering Research Center for Tissue Restoration and Reconstruction, Division of Life Science and State Key Laboratory of Molecular Neuroscience, Division of Biomedical Engineering, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China
| | - J. Zhang
- Department of Chemistry, Hong Kong Branch of Chinese National Engineering Research Center for Tissue Restoration and Reconstruction, Division of Life Science and State Key Laboratory of Molecular Neuroscience, Division of Biomedical Engineering, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China
| | - H. Zhang
- Department of Chemistry, Hong Kong Branch of Chinese National Engineering Research Center for Tissue Restoration and Reconstruction, Division of Life Science and State Key Laboratory of Molecular Neuroscience, Division of Biomedical Engineering, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China
| | - Y. Wang
- Department of Chemistry, Hong Kong Branch of Chinese National Engineering Research Center for Tissue Restoration and Reconstruction, Division of Life Science and State Key Laboratory of Molecular Neuroscience, Division of Biomedical Engineering, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China
| | - C. Chuah
- Institute for NanoScale Science and Technology, College of Science and Engineering, Flinders University, South Australia, 5042, Australia
| | - Y. Tang
- Institute for NanoScale Science and Technology, College of Science and Engineering, Flinders University, South Australia, 5042, Australia
| | - J.W.Y. Lam
- Department of Chemistry, Hong Kong Branch of Chinese National Engineering Research Center for Tissue Restoration and Reconstruction, Division of Life Science and State Key Laboratory of Molecular Neuroscience, Division of Biomedical Engineering, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China
| | - R.T.K. Kwok
- Department of Chemistry, Hong Kong Branch of Chinese National Engineering Research Center for Tissue Restoration and Reconstruction, Division of Life Science and State Key Laboratory of Molecular Neuroscience, Division of Biomedical Engineering, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China
| | - H. Ou
- Key Laboratory of Bioactive Materials Ministry of Education and College of Life Sciences, Nankai University, Tianjin, 300071, China
| | - D. Ding
- Key Laboratory of Bioactive Materials Ministry of Education and College of Life Sciences, Nankai University, Tianjin, 300071, China
| | - B.Z. Tang
- Department of Chemistry, Hong Kong Branch of Chinese National Engineering Research Center for Tissue Restoration and Reconstruction, Division of Life Science and State Key Laboratory of Molecular Neuroscience, Division of Biomedical Engineering, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China
- Center for Aggregation-Induced Emission SCUT-HKUST Joint Research Institute State Key Laboratory of Luminescent Materials and Devices South China University of Technology, Guangzhou, 510640, China
- AIE Institute, Guangzhou Development District, Huangpu, Guangzhou, 510530, China
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Yang E, Huang S, Ran X, Huang Y, Li Z. The 5-year overall survival of cervical cancer in stage IIIC-r was little different to stage I and II: a retrospective analysis from a single center. BMC Cancer 2021; 21:203. [PMID: 33639874 PMCID: PMC7912513 DOI: 10.1186/s12885-021-07890-w] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2020] [Accepted: 01/21/2021] [Indexed: 12/24/2022] Open
Abstract
Background The 2018 International Federation of Gynecology and Obstetrics (FIGO) staging guideline for cervical cancer includes stage IIIC recognized by preoperative radiology (IIIC-r) to state there are lymph nodes metastases (LNM) identified by imaging tools. We aim to explore the reasonability and limitations of stage IIIC-r and try to explore the potential reasons. Methods Electronic medical records were used to identify patients with cervical cancer. According to the new staging guidelines, patients were reclassified and assigned into five cohorts: stage I, stage II, stage IIIC-r, LNM confirmed by pathology (IIIC-p) and LNM detected by radiology and confirmed by pathology (IIIC r + p). Five-year overall survivals were estimated for each cohort. The diagnosis accuracy of computed tomography (CT), magnetic resonance imaging (MRI) and diameter of detected lymph nodes were also evaluated. Results A total of 619 patients were identified. The mean follow-up months were 65 months (95% CI 64.43–65.77) for all patients. By comparison, the 5-year overall survival rates were not statistically different (p = 0.21) among stage IIIC-r, stage I and stage II. While, the rates were both statistical different (p<0.001) among stage IIIC-p, IIIC r + p and stage I and stage II. The sensitivities of CT and MRI in detecting LNM preoperatively were 51.2 and 48.8%. The mean maximum diameter of pelvic lymph nodes detected by CT cohort was 1.2 cm in IIIC-r cohort, and was 1.3 cm in IIIC r + p cohort. While, the mean maximum diameter of pelvic lymph nodes detected by MRI was 1.2 cm in IIIC-r cohort, and was 1.48 cm in IIIC r + p cohort. When the diagnosis efficacy of the diameter of pelvic lymph nodes in detecting LNM were evaluated, the area under the receiver operating characteristic curve (ROC curve) was 0.58 (p = 0.05). Conclusions It seems that the FIGO 2018 staging guideline for cervical cancer is likely to has certain limitations for the classification of those with LNM. CT or MRI, however, has limitations on detecting LNM. It would be better to use more accurate imaging tools to identify LNM in the clinical practices.
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Affiliation(s)
- E Yang
- Department of Gynecology and Obstetrics, West China Second University Hospital, Sichuan University, Chengdu, 610041, People's Republic of China
| | - Shuying Huang
- Department of Gynecology and Obstetrics, West China Second University Hospital, Sichuan University, Chengdu, 610041, People's Republic of China
| | - Xuting Ran
- Department of Gynecology and Obstetrics, West China Second University Hospital, Sichuan University, Chengdu, 610041, People's Republic of China
| | - Yue Huang
- Department of Gynecology and Obstetrics, West China Second University Hospital, Sichuan University, Chengdu, 610041, People's Republic of China
| | - Zhengyu Li
- Department of Gynecology and Obstetrics, West China Second University Hospital, Sichuan University, Chengdu, 610041, People's Republic of China. .,Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, Chengdu, 610041, People's Republic of China.
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Zapardiel I, Alvarez J, Barahona M, Barri P, Boldo A, Bresco P, Gasca I, Jaunarena I, Kucukmetin A, Mancebo G, Otero B, Roldan F, Rovira R, Suarez E, Tejerizo A, Torrent A, Gorostidi M. Utility of Intraoperative Fluorescence Imaging in Gynecologic Surgery: Systematic Review and Consensus Statement. Ann Surg Oncol 2020; 28:3266-3278. [PMID: 33095359 DOI: 10.1245/s10434-020-09222-x] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2020] [Accepted: 09/15/2020] [Indexed: 12/12/2022]
Abstract
BACKGROUND This study aimed to review the current knowledge on the utility of intraoperative fluorescence imaging in gynecologic surgery and to give evidence-based recommendations to improve the quality of care for women who undergo gynecologic surgery. METHODS A computer-based systematic review of the MEDLINE, CENTRAL, Pubmed, EMBASE, and SciSearch databases as well as institutional guidelines was performed. The time limit was set at 2000-2019. For the literature search, PRISMA guidelines were followed. A modified-Delphi method was performed in three rounds by a panel of experts to reach a consensus of conclusions and recommendations. RESULTS Indocyanine green (ICG) is used primarily in gynecology for sentinel node-mapping. In endometrial and cervical cancer, ICG is a feasible, safe, time-efficient, and reliable method for lymphatic mapping, with better bilateral detection rates. Experience in vulvar cancer is more limited, with ICG used together with Tc-99 m as a dual tracer and alone in video endoscopic inguinal lymphadenectomy. In early ovarian cancer, results are still preliminary but promising. Indocyanine green fluorescence imaging also is used for ureteral assessment, allowing intraoperative ureteral visualization, to reduce the risk of ureteral injury during gynecologic surgery. CONCLUSIONS For most gynecologic cancers, ICG fluorescence imaging is considered the tracer of choice for lymphatic mapping. The use of this new technology expands to a better ureteral assessment.
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Affiliation(s)
- Ignacio Zapardiel
- Gynecologic Oncology Unit, La Paz University Hospital-IdiPAZ, Madrid, Spain
| | - Julio Alvarez
- Obstetrics and Gynecology Department, Infanta Sofia University Hospital, Madrid, Spain
| | - Manel Barahona
- Gynecology Department, Puerto Real University Hospital, Cádiz, Spain
| | - Pere Barri
- Gynecologic Surgery Unit, Hospital Quiron Dexeus, Barcelona, Spain
| | - Ana Boldo
- Obstetrics and Gynecology Department, Hospital de la Plana, Castellón, Spain
| | - Pera Bresco
- Gynecology Department, Hospital de Igualada, Barcelona, Spain
| | - Isabel Gasca
- Gynecology Department, Hospital de Valme, Seville, Spain
| | - Ibon Jaunarena
- Gynecologic Unit, Donostia University Hospital-Biodonostia Health Research Institute, Basque Country University, San Sebastián, Spain
| | - Ali Kucukmetin
- Northern Gynaecological Oncology Centre, Queen Elizabeth Hospital, Gateshead, UK
| | - Gloria Mancebo
- Gynecologic Oncology Unit, Hospital Universitario del Mar, Barcelona, Spain
| | - Borja Otero
- Gynecology Department, Hospital Universitario de Cruces, Bilbao, Spain
| | - Fernando Roldan
- Gynecology Department, Hospital Clinico Universitario Lozano Blesa, Saragossa, Spain
| | - Ramón Rovira
- Gynecology Department, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
| | - Enma Suarez
- Gynecology Department, Hospital Universitario Vall d´Hebron, Barcelona, Spain
| | - Alvaro Tejerizo
- Gynecologic Oncology Unit, 12 de Octubre Universitary Hospital, Madrid, Spain
| | - Anna Torrent
- Gynecology Department, Hospital Universitario Son Espases, Majorca, Spain
| | - Mikel Gorostidi
- Gynecologic Unit, Donostia University Hospital-Biodonostia Health Research Institute, Basque Country University, San Sebastián, Spain.
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20
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Cao X, Li K, Xu XL, Deneen KMV, Geng GH, Chen XL. Development of tomographic reconstruction for three-dimensional optical imaging: From the inversion of light propagation to artificial intelligence. Artif Intell Med Imaging 2020; 1:78-86. [DOI: 10.35711/aimi.v1.i2.78] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/05/2020] [Revised: 08/01/2020] [Accepted: 08/21/2020] [Indexed: 02/06/2023] Open
Abstract
Optical molecular tomography (OMT) is an imaging modality which uses an optical signal, especially near-infrared light, to reconstruct the three-dimensional information of the light source in biological tissue. With the advantages of being low-cost, noninvasive and having high sensitivity, OMT has been applied in preclinical and clinical research. However, due to its serious ill-posedness and ill-condition, the solution of OMT requires heavy data analysis and the reconstruction quality is limited. Recently, the artificial intelligence (commonly known as AI)-based methods have been proposed to provide a different tool to solve the OMT problem. In this paper, we review the progress on OMT algorithms, from conventional methods to AI-based methods, and we also give a prospective towards future developments in this domain.
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Affiliation(s)
- Xin Cao
- School of Information Science and Technology, Northwest University, Xi’an 710069, Shaanxi Province, China
| | - Kang Li
- School of Information Science and Technology, Northwest University, Xi’an 710069, Shaanxi Province, China
| | - Xue-Li Xu
- School of Information Science and Technology, Northwest University, Xi’an 710069, Shaanxi Province, China
| | - Karen M von Deneen
- Engineering Research Center of Molecular and Neuro Imaging, Ministry of Education, and School of Life Science and Technology, Xidian University, Xi’an 710126, Shaanxi Province, China
| | - Guo-Hua Geng
- School of Information Science and Technology, Northwest University, Xi’an 710069, Shaanxi Province, China
| | - Xue-Li Chen
- Engineering Research Center of Molecular and Neuro Imaging, Ministry of Education, and School of Life Science and Technology, Xidian University, Xi’an 710126, Shaanxi Province, China
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21
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Haupt K, Medina Rangel PX, Bui BTS. Molecularly Imprinted Polymers: Antibody Mimics for Bioimaging and Therapy. Chem Rev 2020; 120:9554-9582. [PMID: 32786424 DOI: 10.1021/acs.chemrev.0c00428] [Citation(s) in RCA: 238] [Impact Index Per Article: 47.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Molecularly imprinted polymers (MIPs) are tailor-made chemical receptors that recognize and bind target molecules with a high affinity and selectivity. MIPs came into the spotlight in 1993 when they were dubbed "antibody mimics," and ever since, they have been widely studied for the extraction or trapping of chemical pollutants, in immunoassays, and for the design of sensors. Owing to novel synthesis strategies resulting in more biocompatible MIPs in the form of soluble nanogels, these synthetic antibodies have found favor in the biomedical domain since 2010, when for the first time, they were shown to capture and eliminate a toxin in live mice. This review, covering the years 2015-2020, will first describe the rationale behind these antibody mimics, and the different synthesis methods that have been employed for the preparation of MIPs destined for in vitro and in vivo targeting and bioimaging of cancer biomarkers, an emerging and fast-growing area of MIP applications. MIPs have been synthesized for targeting and visualizing glycans and protein-based cell receptors overexpressed in certain diseases, which are well-known biomarkers for example for tumors. When loaded with drugs, the MIPs could locally kill the tumor cells, making them efficient therapeutic agents. We will end the review by reporting how MIPs themselves can act as therapeutics by inhibiting cancer growth. These works mark a new opening in the use of MIPs for antibody therapy and even immunotherapy, as materials of the future in nanomedicine.
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Affiliation(s)
- Karsten Haupt
- Université de Technologie de Compiègne, CNRS Enzyme and Cell Engineering Laboratory, Rue Roger Couttolenc, CS 60319, 60203 Compiègne Cedex, France
| | - Paulina X Medina Rangel
- Université de Technologie de Compiègne, CNRS Enzyme and Cell Engineering Laboratory, Rue Roger Couttolenc, CS 60319, 60203 Compiègne Cedex, France
| | - Bernadette Tse Sum Bui
- Université de Technologie de Compiègne, CNRS Enzyme and Cell Engineering Laboratory, Rue Roger Couttolenc, CS 60319, 60203 Compiègne Cedex, France
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Zaffino P, Moccia S, De Momi E, Spadea MF. A Review on Advances in Intra-operative Imaging for Surgery and Therapy: Imagining the Operating Room of the Future. Ann Biomed Eng 2020; 48:2171-2191. [PMID: 32601951 DOI: 10.1007/s10439-020-02553-6] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2020] [Accepted: 06/17/2020] [Indexed: 12/19/2022]
Abstract
With the advent of Minimally Invasive Surgery (MIS), intra-operative imaging has become crucial for surgery and therapy guidance, allowing to partially compensate for the lack of information typical of MIS. This paper reviews the advancements in both classical (i.e. ultrasounds, X-ray, optical coherence tomography and magnetic resonance imaging) and more recent (i.e. multispectral, photoacoustic and Raman imaging) intra-operative imaging modalities. Each imaging modality was analyzed, focusing on benefits and disadvantages in terms of compatibility with the operating room, costs, acquisition time and image characteristics. Tables are included to summarize this information. New generation of hybrid surgical room and algorithms for real time/in room image processing were also investigated. Each imaging modality has its own (site- and procedure-specific) peculiarities in terms of spatial and temporal resolution, field of view and contrasted tissues. Besides the benefits that each technique offers for guidance, considerations about operators and patient risk, costs, and extra time required for surgical procedures have to be considered. The current trend is to equip surgical rooms with multimodal imaging systems, so as to integrate multiple information for real-time data extraction and computer-assisted processing. The future of surgery is to enhance surgeons eye to minimize intra- and after-surgery adverse events and provide surgeons with all possible support to objectify and optimize the care-delivery process.
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Affiliation(s)
- Paolo Zaffino
- Department of Experimental and Clinical Medicine, Universitá della Magna Graecia, Catanzaro, Italy
| | - Sara Moccia
- Department of Information Engineering (DII), Universitá Politecnica delle Marche, via Brecce Bianche, 12, 60131, Ancona, AN, Italy.
| | - Elena De Momi
- Department of Electronics, Information and Bioengineering (DEIB), Politecnico di Milano, Piazza Leonardo da Vinci, 32, 20133, Milano, MI, Italy
| | - Maria Francesca Spadea
- Department of Experimental and Clinical Medicine, Universitá della Magna Graecia, Catanzaro, Italy
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23
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Advances in image enhancement for sarcoma surgery. Cancer Lett 2020; 483:1-11. [PMID: 32247870 DOI: 10.1016/j.canlet.2020.03.029] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2020] [Revised: 03/19/2020] [Accepted: 03/29/2020] [Indexed: 12/12/2022]
Abstract
The recurrence rate of soft tissue and bone sarcomas strongly correlates to the status of the surgical margin after excision, yet excessive removal of tissue may lead to distinct, otherwise avoidable morbidity. Therefore, adequate margination of sarcomas both pre- and intra-operatively is a clinical necessity that has not yet fully been met. Current guidance for soft-tissue sarcomas recommends an ultrasound scan followed by magnetic resonance imaging (MRI). For bone sarcomas, two plane radiographs are required, followed similarly by an MRI scan. The introduction of more precise imaging modalities may reduce the morbidity associated with sarcoma surgery; the PET-CT and PET-MRI approaches in particular demonstrating high clinical efficacy. Despite advancements in the accuracy in pre-operative imaging, translation of an image to surgical margins is difficult, regularly resulting in wider resection margins than required. For soft tissue sarcomas there is currently no standard technique for image guided resections, while for bone sarcomas fluoroscopy may be used, however margins are not easily discernible during the surgical procedure. Near infra-red (NIR) fluorescence guided surgery offers an intra-operative modality through which complete tumour resection with adequate tumour-free margins may be achieved, while simultaneously minimising surgical morbidity. NIR imaging presents a potentially valuable adjunct to sarcoma surgery. Early reports indicate that it may be able to provide the surgeon with helpful information on anatomy, perfusion, lymphatic drainage, tumour margins and metastases. The use of NIR fluorochromes have also been demonstrated to be well tolerated by patients. However, prior to widespread implementation, studies related to cost-effectiveness and the development of protocols are essential. Nevertheless, NIR imaging may become ubiquitous in the future, carrying the potential to transform the surgical management of sarcoma.
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Indocyanine Green Fluorescence Imaging-Guided Laparoscopic Surgery Could Achieve Radical D3 Dissection in Patients With Advanced Right-Sided Colon Cancer. Dis Colon Rectum 2020; 63:441-449. [PMID: 31996582 DOI: 10.1097/dcr.0000000000001597] [Citation(s) in RCA: 30] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
Abstract
BACKGROUND The optimal lymph node dissection with central vascular ligation is an important part for oncological outcomes after laparoscopic right-sided colon cancer surgery. Few studies have examined the clinical value of indocyanine green fluorescence imaging-guided D3 dissection for right-sided colon cancer. OBJECTIVES We assessed the clinical value of indocyanine green fluorescence imaging-guided laparoscopic surgery in improving the radicality of lymph node dissection for right-sided colon cancer by comparing the outcomes of conventional laparoscopic surgery. DESIGN The data were retrospectively reviewed and analyzed. SETTING This study was conducted at a single university hospital. PATIENTS A 1:2 matched case-control study included 25 patients undergoing fluorescence imaging-guided laparoscopic surgery and 50 patients undergoing conventional laparoscopic surgery for clinical T3 or T4 right-sided colon cancer between June 2016 and December 2017. MAIN OUTCOME MEASURES The extent of D3 dissection and pathological results (tumor stage, lymph node yield, and number of metastatic lymph nodes) were analyzed. RESULTS The 2 groups were similar in baseline characteristics. The numbers of harvested pericolic and intermediate lymph nodes were not different between the 2 groups. The numbers of central lymph nodes (14 vs 7, p < 0.001) and total harvested lymph nodes (39 vs 30, p = 0.003) were significantly higher in the fluorescence group than in the conventional group. In the multivariate analysis, the use of indocyanine green fluorescence imaging was an independently related factor for the retrieval of higher numbers of overall and central lymph nodes. The number of metastatic lymph nodes was not significantly different between the 2 groups. LIMITATIONS The results of this study were limited by its small patient numbers and retrospective nature. CONCLUSIONS Real-time indocyanine green fluorescence imaging of lymph nodes may improve the performance of more radical D3 lymph node dissection during laparoscopic right hemicolectomy for advanced right-sided colon cancer. See Video Abstract at http://links.lww.com/DCR/B150. LA CIRUGÍA LAPAROSCÓPICA GUIADA POR IMÁGENES DE FLUORESCENCIA VERDE INDOCIANINA PODRÍA LOGRAR UNA DISECCIÓN RADICAL D3 EN PACIENTES CON CÁNCER DE COLON AVANZADO DEL LADO DERECHO: La disección óptima de los ganglios linfáticos con ligadura vascular central es una parte importante para los resultados oncológicos después de la cirugía laparoscópica de cáncer de colon del lado derecho. Pocos estudios han examinado el valor clínico de la disección D3 guiada por imágenes de fluorescencia verde indocianina para el cáncer de colon del lado derecho.Evaluamos el valor clínico de la cirugía laparoscópica guiada por imagen de fluorescencia verde indocianina para mejorar la radicalidad de la disección de ganglios linfáticos para el cáncer de colon del lado derecho mediante la comparación de los resultados de la cirugía laparoscópica convencional.Los datos se revisaron y analizaron retrospectivamente.Este estudio se realizó en un solo hospital universitario.Un estudio de casos y controles emparejado 1:2 incluyó a 25 pacientes sometidos a cirugía laparoscópica guiada por imágenes de fluorescencia y 50 pacientes sometidos a cirugía laparoscópica convencional para cáncer de colon derecho clínico T3 o T4 entre Junio de 2016 y Diciembre de 2017.Se analizó el alcance de la disección D3 y los resultados patológicos (estadio tumoral, rendimiento de los ganglios linfáticos y número de ganglios linfáticos metastásicos).Los dos grupos fueron similares en las características basicas. El número de ganglios linfáticos pericólicos e intermedios recolectados no fue diferente entre los dos grupos. El número de ganglios linfáticos centrales (14 vs 7, p < 0.001) y el total de ganglios linfáticos recolectados (39 vs 30, p = 0.003) fueron significativamente mayores en el grupo de fluorescencia que en el grupo convencional. En el análisis multivariante, el uso de imágenes de fluorescencia verde indocianina fue un factor independiente relacionado para la recuperación de un mayor número de ganglios linfáticos centrales y globales. El número de ganglios linfáticos metastásicos no fue significativamente diferente entre los dos grupos.Los resultados de este estudio fueron limitados por su pequeño número de pacientes y su naturaleza retrospectiva.Las imágenes de fluorescencia verde indocianina en tiempo real de los ganglios linfáticos pueden mejorar el rendimiento de la disección más radical de los ganglios linfáticos D3 durante la hemicolectomía derecha laparoscópica para el cáncer de colon avanzado del lado derecho. Consulte Video Resumen en http://links.lww.com/DCR/B150.
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Abstract
The present chapter summarizes progress with optical methods that go beyond human vision. The focus is on two particular technologies: fluorescence molecular imaging and optoacoustic (photoacoustic) imaging. The rationale for the selection of these two methods is that in contrast to optical microscopy techniques, both fluorescence and optoacoustic imaging can achieve large fields of view, i.e., spanning several centimeters in two or three dimensions. Such fields of views relate better to human vision and can visualize large parts of tissue, a necessary premise for clinical detection. Conversely, optical microscopy methods only scan millimeter-sized dimensions or smaller. With such operational capacity, optical microscopy methods need to be guided by another visualization technique in order to scan a very specific area in tissue and typically only provide superficial measurements, i.e., information from depths that are of the order of 0.05-1 mm. This practice has generally limited their clinical applicability to some niche applications, such as optical coherence tomography of the retina. On the other hand, fluorescence molecular imaging and optoacoustic imaging emerge as more global optical imaging methods with wide applications in surgery, endoscopy, and non-invasive clinical imaging, as summarized in the following. The current progress in this field is based on a volume of recent review and other literature that highlights key advances achieved in technology and biomedical applications. Context and figures from references from the authors of this chapter have been used here, as it reflects our general view of the current status of the field.
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Affiliation(s)
- Daniel Razansky
- Faculty of Medicine and Institute of Pharmacology and Toxicology, University of Zurich, Zurich, Switzerland
- Department of Information Technology and Electrical Engineering, Institute for Biomedical Engineering, ETH Zurich, Zurich, Switzerland
| | - Vasilis Ntziachristos
- Technical University of Munich, Ismaningerstr. 22, 81675, Munich, Germany.
- Institute of Biological and Medical Imaging, Helmholtz Zentrum München, Neuherberg, Germany.
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van Beurden F, van Willigen DM, Vojnovic B, van Oosterom MN, Brouwer OR, van der Poel HG, Kobayashi H, van Leeuwen FW, Buckle T. Multi-Wavelength Fluorescence in Image-Guided Surgery, Clinical Feasibility and Future Perspectives. Mol Imaging 2020; 19:1536012120962333. [PMID: 33125289 PMCID: PMC7607779 DOI: 10.1177/1536012120962333] [Citation(s) in RCA: 31] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2020] [Revised: 07/22/2020] [Accepted: 09/01/2020] [Indexed: 12/15/2022] Open
Abstract
With the rise of fluorescence-guided surgery, it has become evident that different types of fluorescence signals can provide value in the surgical setting. Hereby a different range of targets have been pursued in a great variety of surgical indications. One of the future challenges lies in combining complementary fluorescent readouts during one and the same surgical procedure, so-called multi-wavelength fluorescence guidance. In this review we summarize the current clinical state-of-the-art in multi-wavelength fluorescence guidance, basic technical concepts, possible future extensions of existing clinical indications and impact that the technology can bring to clinical care.
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Affiliation(s)
- Florian van Beurden
- Interventional Molecular Imaging Laboratory, Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands
- Department of Urology, The Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands
| | - Danny M. van Willigen
- Interventional Molecular Imaging Laboratory, Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands
| | - Borivoj Vojnovic
- Department of Oncology, Cancer Research UK/MRC Oxford Institute for Radiation Oncology, University of Oxford, Oxford, United Kingdom
| | - Matthias N. van Oosterom
- Interventional Molecular Imaging Laboratory, Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands
- Department of Urology, The Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands
| | - Oscar R. Brouwer
- Interventional Molecular Imaging Laboratory, Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands
- Department of Urology, The Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands
| | - Henk G. van der Poel
- Department of Urology, The Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands
| | - Hisataka Kobayashi
- Molecular Imaging Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
| | - Fijs W.B. van Leeuwen
- Interventional Molecular Imaging Laboratory, Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands
- Department of Urology, The Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands
- Orsi Academy, Melle, Belgium
| | - Tessa Buckle
- Interventional Molecular Imaging Laboratory, Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands
- Department of Urology, The Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands
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Dundr P, Cibula D, Němejcová K, Tichá I, Bártů M, Jakša R. Pathologic Protocols for Sentinel Lymph Nodes Ultrastaging in Cervical Cancer. Arch Pathol Lab Med 2019; 144:1011-1020. [PMID: 31869245 DOI: 10.5858/arpa.2019-0249-ra] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
CONTEXT.— Ultrastaging of sentinel lymph nodes (SLNs) is a crucial aspect in the approach to SLN processing. No consensual protocol for pathologic ultrastaging has been approved by international societies to date. OBJECTIVE.— To provide a review of the ultrastaging protocol and all its aspects related to the processing of SLNs in patients with cervical cancer. DATA SOURCES.— In total, 127 publications reporting data from 9085 cases were identified in the literature. In 24% of studies, the information about SLN processing is entirely missing. No ultrastaging protocol was used in 7% of publications. When described, the differences in all aspects of SLN processing among the studies and institutions are substantial. This includes grossing of the SLN, which is not completely sliced and processed in almost 20% of studies. The reported protocols varied in all aspects of SLN processing, including the thickness of slices (range, 1-5 mm), the number of levels (range, 0-cut out until no tissue left), distance between the levels (range, 40-1000 μm), and number of sections per level (range, 1-5). CONCLUSIONS.— We found substantial differences in protocols used for SLN pathologic ultrastaging, which can impact sensitivity for detection of micrometastases and even small macrometastases. Since the involvement of pelvic lymph nodes is the most important negative prognostic factor, such profound discrepancies influence the referral of patients to adjuvant radiotherapy and could potentially cause treatment failure. It is urgent that international societies agree on a consensual protocol before SLN biopsy without pelvic lymphadenectomy is introduced into routine clinical practice.
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Affiliation(s)
- Pavel Dundr
- From Institute of Pathology (Drs Dundr, Němejcová, Tichá, Bártů, and Jakša) and Gynecologic Oncology Center, Department of Obstetrics and Gynecology (Dr Cibula), First Faculty of Medicine, Charles University and General University Hospital in Prague, Czech Republic
| | - David Cibula
- From Institute of Pathology (Drs Dundr, Němejcová, Tichá, Bártů, and Jakša) and Gynecologic Oncology Center, Department of Obstetrics and Gynecology (Dr Cibula), First Faculty of Medicine, Charles University and General University Hospital in Prague, Czech Republic
| | - Kristýna Němejcová
- From Institute of Pathology (Drs Dundr, Němejcová, Tichá, Bártů, and Jakša) and Gynecologic Oncology Center, Department of Obstetrics and Gynecology (Dr Cibula), First Faculty of Medicine, Charles University and General University Hospital in Prague, Czech Republic
| | - Ivana Tichá
- From Institute of Pathology (Drs Dundr, Němejcová, Tichá, Bártů, and Jakša) and Gynecologic Oncology Center, Department of Obstetrics and Gynecology (Dr Cibula), First Faculty of Medicine, Charles University and General University Hospital in Prague, Czech Republic
| | - Michaela Bártů
- From Institute of Pathology (Drs Dundr, Němejcová, Tichá, Bártů, and Jakša) and Gynecologic Oncology Center, Department of Obstetrics and Gynecology (Dr Cibula), First Faculty of Medicine, Charles University and General University Hospital in Prague, Czech Republic
| | - Radek Jakša
- From Institute of Pathology (Drs Dundr, Němejcová, Tichá, Bártů, and Jakša) and Gynecologic Oncology Center, Department of Obstetrics and Gynecology (Dr Cibula), First Faculty of Medicine, Charles University and General University Hospital in Prague, Czech Republic
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28
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Bogdanov AA, Solovyev ID, Savitsky AP. Sensors for Proteolytic Activity Visualization and Their Application in Animal Models of Human Diseases. BIOCHEMISTRY (MOSCOW) 2019; 84:S1-S18. [PMID: 31213192 DOI: 10.1134/s0006297919140013] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Various sensors designed for optical and photo(opto)acoustic imaging in living systems are becoming essential components of basic and applied biomedical research. Some of them including those developed for determining enzyme activity in vivo are becoming commercially available. These sensors can be used for various fluorescent signal detection methods: from whole body tomography to endoscopy with miniature cameras. Sensor molecules including enzyme-cleavable macromolecules carrying multiple quenched near-infrared fluorophores are able to deliver their payload in vivo and have long circulation time in bloodstream enabling detection of enzyme activity for extended periods of time at low doses of these sensors. In the future, more effective "activated" probes are expected to become available with optimized sensitivity to enzymatic activity, spectral characteristics suitable for intraoperative imaging of surgical field, biocompatibility and lack of immunogenicity and toxicity. New in vivo optical imaging methods such as the fluorescence lifetime and photo(opto)acoustic imaging will contribute to early diagnosis of human diseases. The use of sensors for in vivo optical imaging will include more extensive preclinical applications of experimental therapies. At the same time, the ongoing development and improvement of optical signal detectors as well as the availability of biologically inert and highly specific fluorescent probes will further contribute to the introduction of fluorescence imaging into the clinic.
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Affiliation(s)
- A A Bogdanov
- University of Massachusetts Medical School, Department of Radiology, Laboratory of Molecular Imaging Probes, Worcester, MA 01655, USA. .,A. N. Bach Institute of Biochemistry, Federal Research Center "Fundamentals of Biotechnology", Russian Academy of Sciences, Laboratory of Molecular Imaging, Moscow, 119071, Russia.,Lomonosov Moscow State University, Faculty of Bioengineering and Bioinformatics, Moscow, 119991, Russia
| | - I D Solovyev
- A. N. Bach Institute of Biochemistry, Federal Research Center "Fundamentals of Biotechnology", Russian Academy of Sciences, Laboratory of Molecular Imaging, Moscow, 119071, Russia.,A. N. Bach Institute of Biochemistry, Fundamentals of Biotechnology Federal Research Center, Russian Academy of Sciences, Laboratory of Physical Biochemistry, Moscow, 119071, Russia
| | - A P Savitsky
- A. N. Bach Institute of Biochemistry, Federal Research Center "Fundamentals of Biotechnology", Russian Academy of Sciences, Laboratory of Molecular Imaging, Moscow, 119071, Russia.,A. N. Bach Institute of Biochemistry, Fundamentals of Biotechnology Federal Research Center, Russian Academy of Sciences, Laboratory of Physical Biochemistry, Moscow, 119071, Russia
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29
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Rossi EC. Current state of sentinel lymph nodes for women with endometrial cancer. Int J Gynecol Cancer 2019; 29:613-621. [PMID: 30712017 DOI: 10.1136/ijgc-2018-000075] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2018] [Revised: 11/11/2018] [Accepted: 11/14/2018] [Indexed: 11/04/2022] Open
Abstract
Sentinel lymph node (SLN) biopsy has been investigated as an alternative to conventional pelvic and para-aorticlymphadenectomy for the surgical staging of endometrial cancer. Clinical trials have established the accuracy of sentinel nodes in the detecting metastatic disease. Novel advancements in tracers from the historically favored blue dyes and radio labeled colloids to near infrared imaging of fluorescent dyes has improved the ability to detect sentinel nodes and increased options for surgeons. The uterine cervix has been shown to be a feasible and accurate injection site for tracer, though the potential for under-evaluation of the para-aortic nodes remains a controversy, particularly for high-risk cancers. Additionally, sentinel node evaluation provides qualitatively different information than traditional staging techniques by identifying lymph nodes outside of traditional sampling locations and through the identification of very low volume meta static disease implants, such as isolated tumor cells. It is unclear how this altered staging information should be interpreted, guide the prescription of adjuvant therapy and its impact on long term clinical outcomes such as recurrence and survival. In this review we will discuss the evidence that has supported the use of the SLN technique in the staging of endometrial cancer, the options for surgical technique and the implications of managing the results of staging pathology.
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Affiliation(s)
- Emma C Rossi
- University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
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30
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He M, Jiang Z, Wang C, Hao Z, An J, Shen J. Diagnostic value of near‐infrared or fluorescent indocyanine green guided sentinel lymph node mapping in gastric cancer: A systematic review and meta‐analysis. J Surg Oncol 2018; 118:1243-1256. [DOI: 10.1002/jso.25285] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2018] [Accepted: 10/05/2018] [Indexed: 12/17/2022]
Affiliation(s)
- Meifeng He
- Chengde Medical UniversityChengde Hebei China
| | - Zhanwu Jiang
- Baoding First Central HospitalBaoding Hebei China
| | | | - Zhiwei Hao
- Baoding First Central HospitalBaoding Hebei China
| | - Jie An
- Baoding First Central HospitalBaoding Hebei China
| | - Jiankai Shen
- Baoding First Central HospitalBaoding Hebei China
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31
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Favril S, Abma E, Blasi F, Stock E, Devriendt N, Vanderperren K, de Rooster H. Clinical use of organic near-infrared fluorescent contrast agents in image-guided oncologic procedures and its potential in veterinary oncology. Vet Rec 2018; 183:354. [DOI: 10.1136/vr.104851] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2018] [Revised: 04/11/2018] [Accepted: 04/17/2018] [Indexed: 12/15/2022]
Affiliation(s)
- Sophie Favril
- Small Animal Department, Faculty of Veterinary Medicine; Ghent University; Merelbeke Belgium
- Cancer Research Institute Ghent (CRIG); Ghent Belgium
| | - Eline Abma
- Small Animal Department, Faculty of Veterinary Medicine; Ghent University; Merelbeke Belgium
- Cancer Research Institute Ghent (CRIG); Ghent Belgium
| | - Francesco Blasi
- Ephoran Multi-Imaging Solutions s.r.l.; Colleretto Giacosa Italy
| | - Emmelie Stock
- Department of Medical Imaging of Domestic Animals, Faculty of Veterinary Medicine; Ghent University; Merelbeke Belgium
| | - Nausikaa Devriendt
- Small Animal Department, Faculty of Veterinary Medicine; Ghent University; Merelbeke Belgium
| | - Katrien Vanderperren
- Department of Medical Imaging of Domestic Animals, Faculty of Veterinary Medicine; Ghent University; Merelbeke Belgium
| | - Hilde de Rooster
- Small Animal Department, Faculty of Veterinary Medicine; Ghent University; Merelbeke Belgium
- Cancer Research Institute Ghent (CRIG); Ghent Belgium
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32
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Neumann J, Schmaderer C, Finsterer S, Zimmermann A, Steubl D, Helfen A, Berninger M, Lohöfer F, Rummeny EJ, Meier R, Wildgruber M. Noninvasive quantitative assessment of microcirculatory disorders of the upper extremities with 2D fluorescence optical imaging. Clin Hemorheol Microcirc 2018; 70:69-81. [DOI: 10.3233/ch-170321] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/21/2023]
Affiliation(s)
- Jan Neumann
- Department of Diagnostic and Interventional Radiology, Klinikum rechts der Isar, Technische Universität München, Munich, Germany
| | - Christoph Schmaderer
- Department of Nephrology, Klinikum rechts der Isar, Technische Universität München, Munich, Germany
| | - Sebastian Finsterer
- Department of Diagnostic and Interventional Radiology, Klinikum rechts der Isar, Technische Universität München, Munich, Germany
| | - Alexander Zimmermann
- Department of Vascular and Endovascular Surgery, Klinikum rechts der Isar, Technische Universität München, Munich, Germany
| | - Dominik Steubl
- Department of Nephrology, Klinikum rechts der Isar, Technische Universität München, Munich, Germany
| | - Anne Helfen
- Department of Clinical Radiology, Münster University Hospital, Münster, Germany
| | | | - Fabian Lohöfer
- Department of Diagnostic and Interventional Radiology, Klinikum rechts der Isar, Technische Universität München, Munich, Germany
| | - Ernst J. Rummeny
- Department of Diagnostic and Interventional Radiology, Klinikum rechts der Isar, Technische Universität München, Munich, Germany
| | - Reinhard Meier
- Department of Diagnostic and Interventional Radiology, Klinikum rechts der Isar, Technische Universität München, Munich, Germany
| | - Moritz Wildgruber
- Department of Diagnostic and Interventional Radiology, Klinikum rechts der Isar, Technische Universität München, Munich, Germany
- Department of Clinical Radiology, Münster University Hospital, Münster, Germany
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33
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Singh P, Sahoo GR, Pradhan A. Spatio-temporal map for early cancer detection: Proof of concept. JOURNAL OF BIOPHOTONICS 2018; 11:e201700181. [PMID: 29411946 DOI: 10.1002/jbio.201700181] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/11/2017] [Accepted: 01/21/2018] [Indexed: 06/08/2023]
Abstract
A spatio-temporal map of human cervical tissue is obtained from time-resolved fluorescence images with the dynamic contrast enhanced through principal component analysis (PCA) for clear demarcation of regions of normal and pre-cancerous conditions. Changes in the properties of fluorescence in different environments are captured through fluorescence lifetime maps in the human cervical tissue sample. The correlation embodied in the second principal component (PC) representing sectorial information free of background of the first PC, segregates fluorescence activities, as illustrated in the PC maps. It significantly enhances the contrast of the images which are majorly handicapped by the variations in fluorophore environment. The result is validated on phantoms, mimicking the changes in the environment of normal and abnormal tissues. This spatio-temporal map illustrates the potential of time resolved auto-fluorescence imaging of cervical tissue in combination with PCA to clearly demarcate normal and abnormal regions with enhanced contrast.
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Affiliation(s)
- Pankaj Singh
- Department of Physics, IIT Kanpur, Kanpur, India
| | | | - Asima Pradhan
- Department of Physics, IIT Kanpur, Kanpur, India
- Center for Laser and Photonics, IIT Kanpur, Kanpur, India
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34
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Tummers WS, Willmann JK, Bonsing BA, Vahrmeijer AL, Gambhir SS, Swijnenburg RJ. Advances in Diagnostic and Intraoperative Molecular Imaging of Pancreatic Cancer. Pancreas 2018; 47:675-689. [PMID: 29894417 PMCID: PMC6003672 DOI: 10.1097/mpa.0000000000001075] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Pancreatic ductal adenocarcinoma (PDAC) has a dismal prognosis. To improve outcomes, there is a critical need for improved tools for detection, accurate staging, and resectability assessment. This could improve patient stratification for the most optimal primary treatment modality. Molecular imaging, used in combination with tumor-specific imaging agents, can improve established imaging methods for PDAC. These novel, tumor-specific imaging agents developed to target specific biomarkers have the potential to specifically differentiate between malignant and benign diseases, such as pancreatitis. When these agents are coupled to various types of labels, this type of molecular imaging can provide integrated diagnostic, noninvasive imaging of PDAC as well as image-guided pancreatic surgery. This review provides a detailed overview of the current clinical imaging applications, upcoming molecular imaging strategies for PDAC, and potential targets for imaging, with an emphasis on intraoperative imaging applications.
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Affiliation(s)
- Willemieke S. Tummers
- Department of Radiology, Molecular Imaging Program at Stanford, Stanford University, Stanford, CA. Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands
| | - Juergen K. Willmann
- Department of Radiology, Molecular Imaging Program at Stanford, Stanford University, Stanford, CA. Juergen K. Willmann died January 8, 2018
| | - Bert A. Bonsing
- Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands
| | | | - Sanjiv S. Gambhir
- Address correspondence to: R.J. Swijnenburg, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands (). Tel: +31 71 526 4005, Fax: +31 71 526 6750
| | - Rutger-Jan Swijnenburg
- Department of Surgery, Leiden University Medical Center, Albinusdreef 2, 2300 RC, Leiden, The Netherlands
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van Manen L, Handgraaf HJM, Diana M, Dijkstra J, Ishizawa T, Vahrmeijer AL, Mieog JSD. A practical guide for the use of indocyanine green and methylene blue in fluorescence-guided abdominal surgery. J Surg Oncol 2018; 118:283-300. [PMID: 29938401 PMCID: PMC6175214 DOI: 10.1002/jso.25105] [Citation(s) in RCA: 200] [Impact Index Per Article: 28.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2018] [Accepted: 04/21/2018] [Indexed: 12/14/2022]
Abstract
Near-infrared (NIR) fluorescence imaging is gaining clinical acceptance over the last years and has been used for detection of lymph nodes, several tumor types, vital structures and tissue perfusion. This review focuses on NIR fluorescence imaging with indocyanine green and methylene blue for different clinical applications in abdominal surgery with an emphasis on oncology, based on a systematic literature search. Furthermore, practical information on doses, injection times, and intraoperative use are provided.
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Affiliation(s)
- Labrinus van Manen
- Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands
| | | | - Michele Diana
- IHU-Strasbourg, Institute of Image-Guided Surgery, Strasbourg, France.,IRCAD, Research Institute against Cancer of the Digestive System, Strasbourg, France.,Department of General, Digestive and Endocrine Surgery, University Hospital of Strasbourg, Strasbourg, France
| | - Jouke Dijkstra
- Division of Image Processing, Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands
| | - Takeaki Ishizawa
- Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, University of Tokyo, Tokyo, Japan
| | | | - Jan Sven David Mieog
- Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands
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36
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Determination of the surgical margin in laparoscopic liver resections using infrared indocyanine green fluorescence. Langenbecks Arch Surg 2018; 403:671-680. [DOI: 10.1007/s00423-018-1685-y] [Citation(s) in RCA: 58] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2017] [Accepted: 05/29/2018] [Indexed: 01/06/2023]
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Perissinotti A, Rietbergen DDD, Vidal-Sicart S, Riera AA, Olmos RA. Melanoma & nuclear medicine: new insights & advances. Melanoma Manag 2018; 5:MMT06. [PMID: 30190932 PMCID: PMC6122522 DOI: 10.2217/mmt-2017-0022] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2017] [Accepted: 03/29/2018] [Indexed: 12/16/2022] Open
Abstract
The contribution of nuclear medicine to management of melanoma patients is increasing. In intermediate-thickness N0 melanomas, lymphoscintigraphy provides a roadmap for sentinel node biopsy. With the introduction of single-photon emission computed tomography images with integrated computed tomography (SPECT/CT), 3D anatomic environments for accurate surgical planning are now possible. Sentinel node identification in intricate anatomical areas (pelvic cavity, head/neck) has been improved using hybrid radioactive/fluorescent tracers, preoperative lymphoscintigraphy and SPECT/CT together with modern intraoperative portable imaging technologies for surgical navigation (free-hand SPECT, portable gamma cameras). Furthermore, PET/CT today provides 3D roadmaps to resect 18F-fluorodeoxyglucose-avid melanoma lesions. Simultaneously, in advanced-stage melanoma and recurrences, 18F-fluorodeoxyglucose-PET/CT is useful in clinical staging and treatment decision as well as in the evaluation of therapy response. In this article, we review new insights and recent nuclear medicine advances in the management of melanoma patients.
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Affiliation(s)
- Andrés Perissinotti
- Department of Nuclear Medicine, Hospital Clinic, C/Villarroel 170, 08036 Barcelona, Spain
| | - Daphne DD Rietbergen
- Nuclear Medicine Section & Interventional Molecular Imaging Laboratory, Department of Radiology, Leiden University Medical Centre, Albinusdreef 2, PO Box 9600, 2300 RC, Leiden, The Netherlands
| | - Sergi Vidal-Sicart
- Department of Nuclear Medicine, Hospital Clinic, C/Villarroel 170, 08036 Barcelona, Spain
| | - Ana A Riera
- Department of Nuclear Medicine, Hospital Universitario Nuestra Señora de la Candelaria, Carretera del Rosario 145, 08010 SC de Tenerife, Spain
| | - Renato A Valdés Olmos
- Nuclear Medicine Section & Interventional Molecular Imaging Laboratory, Department of Radiology, Leiden University Medical Centre, Albinusdreef 2, PO Box 9600, 2300 RC, Leiden, The Netherlands
- Department of Nuclear Medicine, Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands
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38
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Li X, Schumann C, Albarqi HA, Lee CJ, Alani AWG, Bracha S, Milovancev M, Taratula O, Taratula O. A Tumor-Activatable Theranostic Nanomedicine Platform for NIR Fluorescence-Guided Surgery and Combinatorial Phototherapy. Am J Cancer Res 2018; 8:767-784. [PMID: 29344305 PMCID: PMC5771092 DOI: 10.7150/thno.21209] [Citation(s) in RCA: 62] [Impact Index Per Article: 8.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2017] [Accepted: 11/09/2017] [Indexed: 11/06/2022] Open
Abstract
Fluorescence image-guided surgery combined with intraoperative therapeutic modalities has great potential for intraoperative detection of oncologic targets and eradication of unresectable cancer residues. Therefore, we have developed an activatable theranostic nanoplatform that can be used concurrently for two purposes: (1) tumor delineation with real-time near infrared (NIR) fluorescence signal during surgery, and (2) intraoperative targeted treatment to further eliminate unresected disease sites by non-toxic phototherapy. Methods: The developed nanoplatform is based on a single agent, silicon naphthalocyanine (SiNc), encapsulated in biodegradable PEG-PCL (poly (ethylene glycol)-b-poly(ɛ-caprolactone)) nanoparticles. It is engineered to be non-fluorescent initially via dense SiNc packing within the nanoparticle's hydrophobic core, with NIR fluorescence activation after accumulation at the tumor site. The activatable nanoplatform was evaluated in vitro and in two different murine cancer models, including an ovarian intraperitoneal metastasis-mimicking model. Furthermore, fluorescence image-guided surgery mediated by this nanoplatform was performed on the employed animal models using a Fluobeam® 800 imaging system. Finally, the phototherapeutic efficacy of the developed nanoplatform was demonstrated in vivo. Results: Our in vitro data suggest that the intracellular environment of cancer cells is capable of compromising the integrity of self-assembled nanoparticles and thus causes disruption of the tight dye packing inside the hydrophobic cores and activation of the NIR fluorescence. Animal studies demonstrated accumulation of activatable nanoparticles at the tumor site following systemic administration, as well as release and fluorescence recovery of SiNc from the polymeric carrier. It was also validated that the developed nanoparticles are compatible with the intraoperative imaging system Fluobeam® 800, and nanoparticle-mediated image-guided surgery provides successful resection of cancer tumors. Finally, in vivo studies revealed that combinatorial phototherapy mediated by the nanoparticles could efficiently eradicate chemoresistant ovarian cancer tumors. Conclusion: The revealed properties of the activatable nanoplatform make it highly promising for further application in clinical image-guided surgery and combined phototherapy, facilitating a potential translation to clinical studies.
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van Oosterom MN, Meershoek P, KleinJan GH, Hendricksen K, Navab N, van de Velde CJH, van der Poel HG, van Leeuwen FWB. Navigation of Fluorescence Cameras during Soft Tissue Surgery-Is it Possible to Use a Single Navigation Setup for Various Open and Laparoscopic Urological Surgery Applications? J Urol 2017; 199:1061-1068. [PMID: 29174485 DOI: 10.1016/j.juro.2017.09.160] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/02/2017] [Indexed: 01/09/2023]
Abstract
PURPOSE Real-time visualization fluorescence imaging can guide surgeons during tissue resection. Unfortunately tissue induced signal attenuation limits the value of this technique to superficial applications. By positioning the fluorescence camera via a dedicated navigation setup we reasoned that the technology could be made compatible with deeper lesions, increasing its impact on clinical care. Such an impact would benefit from the ability to implement the navigation technology in different surgical settings. For that reason we evaluated whether a single fluorescence camera could be navigated toward targeted lesions during open and laparoscopic surgery. MATERIALS AND METHODS A fluorescence camera with scopes available for open and laparoscopic procedures was integrated with a navigation platform. Lymph nodes identified on SPECT/CT (single photon emission computerized tomography/computerized tomography) or free-hand single photon emission computerized tomography acted as navigation targets and were displayed as augmented overlays in the fluorescence camera video feed. The accuracy of this setup was evaluated in a phantom study of 4 scans per single photon emission computerized tomography imaging modality. This was followed by 4 first in human translations into sentinel lymph node biopsy procedures for penile (open surgery) and prostate (laparoscopic surgery) cancer. RESULTS Overall the phantom studies revealed a tool-target distance accuracy of 2.1 mm for SPECT/CT and 3.2 mm for freehand single photon emission computerized tomography, and an augmented reality registration accuracy of 1.1 and 2.2 mm, respectively. Subsequently open and laparoscopic navigation efforts were accurate enough to localize the fluorescence signals of the targeted tissues in vivo. CONCLUSIONS The phantom and human studies performed suggested that the single navigation setup is applicable in various open and laparoscopic urological surgery applications. Further evaluation in larger patient groups with a greater variety of malignancies is recommended to strengthen these results.
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Affiliation(s)
- Matthias N van Oosterom
- Interventional Molecular Imaging Laboratory, Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands; Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands
| | - Philippa Meershoek
- Interventional Molecular Imaging Laboratory, Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands; Department of Urology, The Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands
| | - Gijs H KleinJan
- Interventional Molecular Imaging Laboratory, Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands; Department of Urology, The Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands
| | - Kees Hendricksen
- Department of Urology, The Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands
| | - Nassir Navab
- Computer Aided Medical Procedures, Technische Universität München, Institut für Informatik, Garching bei München, Germany; Computer Aided Medical Procedures, Johns Hopkins University, Baltimore, Maryland
| | | | - Henk G van der Poel
- Department of Urology, The Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands
| | - Fijs W B van Leeuwen
- Interventional Molecular Imaging Laboratory, Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands; Department of Urology, The Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands.
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40
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Arlauckas SP, Kumar M, Popov AV, Poptani H, Delikatny EJ. Near infrared fluorescent imaging of choline kinase alpha expression and inhibition in breast tumors. Oncotarget 2017; 8:16518-16530. [PMID: 28157707 PMCID: PMC5369982 DOI: 10.18632/oncotarget.14965] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2016] [Accepted: 01/16/2017] [Indexed: 12/23/2022] Open
Abstract
Choline kinase alpha (ChoKα) overexpression is associated with an aggressive tumor phenotype. ChoKα inhibitors induce apoptosis in tumors, however validation of their specificity is difficult in vivo. We report the use of optical imaging to assess ChoKα status in cells and in vivo using JAS239, a carbocyanine-based ChoKα inhibitor with inherent near infrared fluorescence. JAS239 attenuated choline phosphorylation and viability in a panel of human breast cancer cell lines. Antibody blockade prevented cellular retention of JAS239 indicating direct interaction with ChoKα independent of the choline transporters and catabolic choline pathways. In mice bearing orthotopic MCF7 breast xenografts, optical imaging with JAS239 distinguished tumors overexpressing ChoKα from their empty vector counterparts and delineated tumor margins. Pharmacological inhibition of ChoK by the established inhibitor MN58b led to a growth inhibition in 4175-Luc+ tumors that was accompanied by concomitant reduction in JAS239 uptake and decreased total choline metabolite levels as measured using magnetic resonance spectroscopy. At higher therapeutic doses, JAS239 was as effective as MN58b at arresting tumor growth and inducing apoptosis in MDA-MB-231 tumors, significantly reducing tumor choline below baseline levels without observable systemic toxicity. These data introduce a new method to monitor therapeutically effective inhibitors of choline metabolism in breast cancer using a small molecule companion diagnostic.
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Affiliation(s)
- Sean P Arlauckas
- Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States
| | - Manoj Kumar
- Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States
| | - Anatoliy V Popov
- Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States
| | - Harish Poptani
- Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States.,Department of Cellular and Molecular Physiology, Institute of Regenerative Medicine, University of Liverpool, Liverpool, United Kingdom
| | - Edward J Delikatny
- Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States
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Buda A, Di Martino G, De Ponti E, Passoni P, Sina F, Reato C, Vecchione F, Giuliani D. Laparoscopic Sentinel Node Mapping in Cervical and Endometrial Malignancies: A Case-Control Study Comparing Two Near-Infrared Fluorescence Systems. J Minim Invasive Gynecol 2017; 25:93-98. [PMID: 28807805 DOI: 10.1016/j.jmig.2017.08.011] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2017] [Revised: 08/06/2017] [Accepted: 08/07/2017] [Indexed: 01/16/2023]
Abstract
STUDY OBJECTIVE The goal of this study was to evaluate the intraoperative and perioperative surgical outcomes of 2 different florescence systems commonly used for sentinel lymph node (SLN) mapping in women with early-stage cervical cancer or endometrial cancer. DESIGN Case-control study (Canadian Task Force classification II-2). SETTING The Gynecology Oncology Surgical Unit of the San Gerardo Hospital, Italy. PATIENTS Thirty-four consecutive women with early stage-cervical cancer (stage IA-1B1) or apparent confined stage I endometrial cancer were included in the study. INTERVENTIONS Between October 2016 and May 2017, 34 patients underwent laparoscopic surgery with SLN mapping using indocyanine green dye: 22 women were mapped with the Storz 1S system (Karl Storz Endoscopy, Tuttlingen, Germany; Group A), whereas 12 women underwent planned surgery with the Novadaq PinPoint system (Novadaq, Mississauga, Ontario, Canada; Group B). MEASUREMENT AND MAIN RESULTS We compared the surgical and perioperative outcomes of Group A and Group B. Patients in Group B had a shorter duration of the SLN mapping time than those in Group A (p = .0003). The median number of SLNs removed was 2 (range, 0-5) in Group A and 2 (range, 1-3) in Group B (p = .501). Bilateral mapping was 77.3% in Group A and 83.3% in Group B (p = .334), respectively. No differences were recorded in terms of body mass index, length of hospital stay, type of tumor, bilateral mapping, or number of lymph nodes removed. Body mass index was found to have no impact on the duration of the mapping (p = .353). CONCLUSION From our preliminary experience we can conclude that both fluorescence systems are valid and applicable for SLN detection in the case of early-stage cervical or endometrial cancer. The PinPoint system seems to allow surgeons easier and faster identification of the SLNs, particularly in endometrial cancer patients.
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Affiliation(s)
- Alessandro Buda
- Gynecologic Oncology Unit, Department of Obstetrics and Gynecology, ASST-Monza, San Gerardo Hospital, Monza, Italy.
| | - Giampaolo Di Martino
- Gynecologic Oncology Unit, Department of Obstetrics and Gynecology, ASST-Monza, San Gerardo Hospital, Monza, Italy
| | - Elena De Ponti
- Department of Medical Physics, ASST-Monza, San Gerardo Hospital, Monza, Italy
| | - Paolo Passoni
- Gynecologic Oncology Unit, Department of Obstetrics and Gynecology, ASST-Monza, San Gerardo Hospital, Monza, Italy
| | - Federica Sina
- Gynecologic Oncology Unit, Department of Obstetrics and Gynecology, ASST-Monza, San Gerardo Hospital, Monza, Italy
| | - Claudio Reato
- Gynecologic Oncology Unit, Department of Obstetrics and Gynecology, ASST-Monza, San Gerardo Hospital, Monza, Italy
| | - Francesca Vecchione
- Gynecologic Oncology Unit, Department of Obstetrics and Gynecology, ASST-Monza, San Gerardo Hospital, Monza, Italy
| | - Daniela Giuliani
- Gynecologic Oncology Unit, Department of Obstetrics and Gynecology, ASST-Monza, San Gerardo Hospital, Monza, Italy
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Role of ICG- 99mTc-nanocolloid for sentinel lymph node detection in cervical cancer: a pilot study. Eur J Nucl Med Mol Imaging 2017; 44:1853-1861. [PMID: 28492965 DOI: 10.1007/s00259-017-3706-4] [Citation(s) in RCA: 43] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2017] [Accepted: 04/11/2017] [Indexed: 10/19/2022]
Abstract
PURPOSE Sentinel lymph node biopsy (SLNB) can be used for nodal staging in early cervical cancer. For this purpose, the tracers most commonly used are radiotracers based on technetium. For the last decade, indocyanine green (ICG) has been used as a tracer for SLNB in other malignancies with excellent results and, more recently, a combination of ICG and a radiotracer has been shown to have the advantages of both tracers. The aim of this study was to evaluate the role of ICG-99mTc-nanocolloid in SLN detection in patients with cervical cancer. METHODS This prospective study included 16 patients with cervical cancer. The hybrid tracer was injected the day (19-21 h) before surgery for planar and SPECT/CT lymphoscintigraphy. Blue dye was administered periorificially in 14 patients. SLNs were removed according to their distribution on lymphoscintigraphy and when radioactive, fluorescent and/or stained with blue dye. Nodal specimens were pathologically analysed for metastases including by immunochemistry. RESULTS Lymphoscintigraphy and SPECT/CT showed drainage in all patients. A total of 69 SLNs were removed, of which 66 were detected by their radioactivity signal and 67 by their fluorescence signal. Blue dye identified only 35 SLNs in 12 of the 14 patients (85.7%). All patients showed bilateral pelvic drainage. Micrometastases were diagnosed in two patients, and were the only lymphatic nodes involved. CONCLUSIONS SLNB with ICG-99mTc-nanocolloid is feasible and safe in patients with early cervical cancer. This hybrid tracer provided bilateral SLN detection in all patients and a higher detection rate than blue dye, so it could become an alternative to the combined technique.
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New procedures for the identification of sentinel lymph node: shaping the horizon of future management in early stage uterine cervical cancer. Updates Surg 2017; 69:383-388. [DOI: 10.1007/s13304-017-0456-6] [Citation(s) in RCA: 33] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2017] [Accepted: 04/20/2017] [Indexed: 11/24/2022]
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Göppner D, Nekwasil S, Jellestad A, Sachse A, Schönborn K, Gollnick H. Indocyanine green‐assisted sentinel lymph node biopsy in melanoma using the “FOVIS“ system. J Dtsch Dermatol Ges 2017; 15:169-178. [DOI: 10.1111/ddg.12794] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2015] [Accepted: 07/08/2015] [Indexed: 12/22/2022]
Affiliation(s)
- Daniela Göppner
- Department of Dermatology and VenereologyOtto von Guericke University Magdeburg Germany
| | - Stephan Nekwasil
- Department of Dermatology and VenereologyOtto von Guericke University Magdeburg Germany
| | - Anne Jellestad
- Department of Dermatology and VenereologyOtto von Guericke University Magdeburg Germany
| | | | | | - Harald Gollnick
- Department of Dermatology and VenereologyOtto von Guericke University Magdeburg Germany
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45
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Göppner D, Nekwasil S, Jellestad A, Sachse A, Schönborn K, Gollnick H. Sentinel‐Lymphknoten‐Biopsie des Melanoms mittels Indocyaningrün und „FOVIS“‐System. J Dtsch Dermatol Ges 2017; 15:169-179. [DOI: 10.1111/ddg.12794_g] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2015] [Accepted: 07/08/2015] [Indexed: 11/29/2022]
Affiliation(s)
- Daniela Göppner
- Klinik für Dermatologie und VenerologieOtto‐von‐Guericke‐Universität Magdeburg
| | - Stephan Nekwasil
- Klinik für Dermatologie und VenerologieOtto‐von‐Guericke‐Universität Magdeburg
| | - Anne Jellestad
- Klinik für Dermatologie und VenerologieOtto‐von‐Guericke‐Universität Magdeburg
| | | | | | - Harald Gollnick
- Klinik für Dermatologie und VenerologieOtto‐von‐Guericke‐Universität Magdeburg
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Rychlik A, Marin S, De Santiago J, Zapardiel I. Utility of Laparoscopic Indocyanine Green-Guided Sentinel Node Biopsy in Open Cervical Cancer Surgery. Int J Gynecol Cancer 2016; 26:1288-9. [PMID: 27643651 DOI: 10.1097/igc.0000000000000752] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022] Open
Abstract
OBJECTIVE Multiple tracers have been used to improve lymphatic mapping and to reduce the false-negative rate of the sentinel node detection in gynecologic cancers. Nowadays, 99mTc colloids combined with blue-dye technique is the most extended technique. New alternatives such as the fluorescent indocyanine green and near-infrared fluorescent imaging detection have been introduced in lymphatic mapping staging procedures because of its easier visualization compared with the previous tracers. METHODS We used the laparoscopic infrared camera for the indocyanine green-guided sentinel node biopsy in a laparotomic radical hysterectomy in a pregnant patient after a cesarean section, with the aim of improving the detection rate of sentinel node biopsy in open surgery. RESULTS The technique was used in the first patient with accurate detection of sentinel node and no complications during the procedure. CONCLUSIONS The use of laparoscopic indocyanine green in open surgery may be a useful tool for the detection of sentinel node biopsy.
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Affiliation(s)
- Agnieszka Rychlik
- Gynecologic Oncology Unit, La Paz University Hospital, Madrid, Spain
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47
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Anastasopoulou M, Koch M, Gorpas D, Karlas A, Klemm U, Garcia-Allende PB, Ntziachristos V. Comprehensive phantom for interventional fluorescence molecular imaging. JOURNAL OF BIOMEDICAL OPTICS 2016; 21:091309. [PMID: 27304578 DOI: 10.1117/1.jbo.21.9.091309] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/30/2016] [Accepted: 05/23/2016] [Indexed: 05/03/2023]
Abstract
Fluorescence imaging has been considered for over a half-century as a modality that could assist surgical guidance and visualization. The administration of fluorescent molecules with sensitivity to disease biomarkers and their imaging using a fluorescence camera can outline pathophysiological parameters of tissue invisible to the human eye during operation. The advent of fluorescent agents that target specific cellular responses and molecular pathways of disease has facilitated the intraoperative identification of cancer with improved sensitivity and specificity over nonspecific fluorescent dyes that only outline the vascular system and enhanced permeability effects. With these new abilities come unique requirements for developing phantoms to calibrate imaging systems and algorithms. We briefly review herein progress with fluorescence phantoms employed to validate fluorescence imaging systems and results. We identify current limitations and discuss the level of phantom complexity that may be required for developing a universal strategy for fluorescence imaging calibration. Finally, we present a phantom design that could be used as a tool for interlaboratory system performance evaluation.
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Affiliation(s)
- Maria Anastasopoulou
- Helmholtz Zentrum München, Institute for Biological and Medical Imaging, Ingolstädter Landstraße 1, Neuherberg D-85764 GermanybTechnical University Munich, Chair for Biological Imaging, Arcisstraße 21, Munich D-80333, Germany
| | - Maximilian Koch
- Helmholtz Zentrum München, Institute for Biological and Medical Imaging, Ingolstädter Landstraße 1, Neuherberg D-85764 GermanybTechnical University Munich, Chair for Biological Imaging, Arcisstraße 21, Munich D-80333, Germany
| | - Dimitris Gorpas
- Helmholtz Zentrum München, Institute for Biological and Medical Imaging, Ingolstädter Landstraße 1, Neuherberg D-85764 GermanybTechnical University Munich, Chair for Biological Imaging, Arcisstraße 21, Munich D-80333, Germany
| | - Angelos Karlas
- Helmholtz Zentrum München, Institute for Biological and Medical Imaging, Ingolstädter Landstraße 1, Neuherberg D-85764 GermanybTechnical University Munich, Chair for Biological Imaging, Arcisstraße 21, Munich D-80333, Germany
| | - Uwe Klemm
- Helmholtz Zentrum München, Institute for Biological and Medical Imaging, Ingolstädter Landstraße 1, Neuherberg D-85764 Germany
| | - Pilar Beatriz Garcia-Allende
- Helmholtz Zentrum München, Institute for Biological and Medical Imaging, Ingolstädter Landstraße 1, Neuherberg D-85764 GermanybTechnical University Munich, Chair for Biological Imaging, Arcisstraße 21, Munich D-80333, Germany
| | - Vasilis Ntziachristos
- Helmholtz Zentrum München, Institute for Biological and Medical Imaging, Ingolstädter Landstraße 1, Neuherberg D-85764 GermanybTechnical University Munich, Chair for Biological Imaging, Arcisstraße 21, Munich D-80333, Germany
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He K, Mao Y, Ye J, An Y, Jiang S, Chi C, Tian J. A novel wireless wearable fluorescence image-guided surgery system. ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY. IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY. ANNUAL INTERNATIONAL CONFERENCE 2016; 2016:5208-5211. [PMID: 28269438 DOI: 10.1109/embc.2016.7591901] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/06/2023]
Abstract
Segmentectomy using indocyanine green (ICG) has become a primary treatment option to achieve a complete resection and preserve lung function in early-stage lung cancer. However, owing to a lack of appropriate intraoperative imaging systems, it is a huge challenge for surgeons to identify the intersegmental plane during the operation, leading to poor prognosis. Thus, we developed a novel wireless wearable fluorescence image-guided surgery system (LIGHTEN) for fast and accurate identification of intersegmental planes in human patients. The system consists of a handle, light source, Google glass and laptop. Application software is written to capture clear real-time images and Google glass is adopted to display with augmented reality. Twelve in vivo studies of pulmonary segmentectomy in swine by intravenous injection of ICG were conducted to test the performance of the system. A distinct black-and-white transition zone image was observed and displayed simultaneously on the Google glass in all swine. The results demonstrated that surgeons using LIGHTEN can effortlessly and quickly discern intersegmental planes during the operation. Our system has enormous potential in helping surgeons to precisely identify intersegmental planes with mobility and high-sensitivity.
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49
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Iqbal H, Pan Q. Image guided surgery in the management of head and neck cancer. Oral Oncol 2016; 57:32-9. [DOI: 10.1016/j.oraloncology.2016.04.007] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2015] [Revised: 04/11/2016] [Accepted: 04/12/2016] [Indexed: 12/15/2022]
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50
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Porcu EP, Salis A, Gavini E, Rassu G, Maestri M, Giunchedi P. Indocyanine green delivery systems for tumour detection and treatments. Biotechnol Adv 2016; 34:768-789. [PMID: 27090752 DOI: 10.1016/j.biotechadv.2016.04.001] [Citation(s) in RCA: 118] [Impact Index Per Article: 13.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2015] [Revised: 03/31/2016] [Accepted: 04/01/2016] [Indexed: 01/16/2023]
Abstract
Indocyanine green (ICG) is a cyanine compound that displays fluorescent properties in the near infrared region. This dye is employed for numerous indications but nowadays its major application field regards tumour diagnosis and treatments. Optical imaging by near infrared fluorescence provides news opportunities for oncologic surgery. The imaging of ICG can be useful for intraoperative identification of several solid tumours and metastases, and sentinel lymph node detection. In addition, ICG can be used as an agent for the destruction of malignant tissue, by virtue of the production of reactive oxygen species and/or induction of a hyperthermia effect under irradiation. Nevertheless, ICG shows several drawbacks, which limit its clinical application. Several formulative strategies have been studied to overcome these problems. The rationale of the development of ICG containing drug delivery systems is to enhance the in vivo stability and biodistribution profile of this dye, allowing tumour accumulation and resulting in better efficacy. In this review, ICG containing nano-sized carriers are classified based on their chemical composition and structure. In addition to nanosystems, different formulations including hydrogel, microsystems and others loaded with ICG will be illustrated. In particular, this report describes the preparation, in vitro characterization and in vivo application of ICG platforms for cancer imaging and treatment. The promising results of all systems confirm their clinical utility but further studies are required prior to evaluating the formulations in human trials.
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Affiliation(s)
- Elena P Porcu
- PhD in Experimental Medicine, Department of Diagnostic, Paediatric, Clinical and Surgical Science, Pavia, Italy
| | - Andrea Salis
- University of Sassari, Department of Chemistry and Pharmacy, Sassari, Italy
| | - Elisabetta Gavini
- University of Sassari, Department of Chemistry and Pharmacy, Sassari, Italy
| | - Giovanna Rassu
- University of Sassari, Department of Chemistry and Pharmacy, Sassari, Italy
| | | | - Paolo Giunchedi
- University of Sassari, Department of Chemistry and Pharmacy, Sassari, Italy.
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