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De Simone B, Abu-Zidan FM, Boni L, Castillo AMG, Cassinotti E, Corradi F, Di Maggio F, Ashraf H, Baiocchi GL, Tarasconi A, Bonafede M, Truong H, De'Angelis N, Diana M, Coimbra R, Balogh ZJ, Chouillard E, Coccolini F, Kelly MD, Di Saverio S, Di Meo G, Isik A, Leppäniemi A, Litvin A, Moore EE, Pasculli A, Sartelli M, Podda M, Testini M, Wani I, Sakakushev B, Shelat VG, Weber D, Galante JM, Ansaloni L, Agnoletti V, Regimbeau JM, Garulli G, Kirkpatrick AL, Biffl WL, Catena F. Indocyanine green fluorescence-guided surgery in the emergency setting: the WSES international consensus position paper. World J Emerg Surg 2025; 20:13. [PMID: 39948641 PMCID: PMC11823064 DOI: 10.1186/s13017-025-00575-w] [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: 11/14/2024] [Accepted: 01/04/2025] [Indexed: 02/16/2025] Open
Abstract
BACKGROUND Decision-making in emergency settings is inherently complex, requiring surgeons to rapidly evaluate various clinical, diagnostic, and environmental factors. The primary objective is to assess a patient's risk for adverse outcomes while balancing diagnoses, management strategies, and available resources. Recently, indocyanine green (ICG) fluorescence imaging has emerged as a valuable tool to enhance surgical vision, demonstrating proven benefits in elective surgeries. AIM This consensus paper provides evidence-based and expert opinion-based recommendations for the standardized use of ICG fluorescence imaging in emergency settings. METHODS Using the PICO framework, the consensus coordinator identified key research areas, topics, and questions regarding the implementation of ICG fluorescence-guided surgery in emergencies. A systematic literature review was conducted, and evidence was evaluated using the GRADE criteria. A panel of expert surgeons reviewed and refined statements and recommendations through a Delphi consensus process, culminating in final approval. RESULTS ICG fluorescence imaging, including angiography and cholangiography, improves intraoperative decision-making in emergency surgeries, potentially reducing procedure duration, complications, and hospital stays. Optimal use requires careful consideration of dosage and timing due to limited tissue penetration (5-10 mm) and variable performance in patients with significant inflammation, scarring, or obesity. ICG is contraindicated in patients with known allergies to iodine or iodine-based contrast agents. Successful implementation depends on appropriate training, availability of equipment, and careful patient selection. CONCLUSIONS Advanced technologies and intraoperative navigation techniques, such as ICG fluorescence-guided surgery, should be prioritized in emergency surgery to improve outcomes. This technology exemplifies precision surgery by enhancing minimally invasive approaches and providing superior real-time evaluation of bowel viability and biliary structures-areas traditionally reliant on the surgeon's visual assessment. Its adoption in emergency settings requires proper training, equipment availability, and standardized protocols. Further research is needed to evaluate cost-effectiveness and expand its applications in urgent surgical procedures.
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Affiliation(s)
- Belinda De Simone
- Department of Emergency and General Minimally Invasive Surgery, Infermi Hospital, AUSL Romagna, Rimini, Italy.
- Department of Theoretical and Applied Sciences, eCampus University, Novedrate, CO, Italy.
| | - Fikri M Abu-Zidan
- Department of Surgery, College of Medicine and Health Sciences, United Arab Emirates University, Al‑Ain, UAE
| | - Luigi Boni
- Department of General and Minimally Invasive Surgery, Fondazione IRCCS - Ca' Granda - Ospedale Maggiore Policlinico di Milano, Milan, Italy
| | - Ana Maria Gonzalez Castillo
- Emergency Surgery Unit, Department of General Surgery, Pompeu Fabra University, Hospital del Mar, Barcelona, Spain
| | - Elisa Cassinotti
- Department of General and Minimally Invasive Surgery, Fondazione IRCCS - Ca' Granda - Ospedale Maggiore Policlinico di Milano, Milan, Italy
| | - Francesco Corradi
- Department of Surgical, Medical andMolecularPathology and Critical Care Medicine, University of Pisa, Pisa, Italy
| | - Francesco Di Maggio
- Upper Gastro-Intestinal Surgery Unit, Department of General Surgery, Croydon University Hospital, London, UK
| | - Hajra Ashraf
- Upper Gastro-Intestinal Surgery Unit, Department of General Surgery, Croydon University Hospital, London, UK
| | - Gian Luca Baiocchi
- Unit of General Surgery, Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy
| | | | | | - Hung Truong
- Acute Care and Minimally Invasive Surgery, Scripps Memorial Hospital - La Jolla, Green, and Encinitas, La Jolla, USA
| | - Nicola De'Angelis
- Unit of Robotic and Minimally Invasive Digestive Surgery, Ferrara University Hospital, Ferrara, Italy
| | - Michele Diana
- Department of Surgery, University Hospital of Geneva, 1205, Geneva, Switzerland
- ICube Laboratory, Photonics Instrumentation for Health, 67034, Strasbourg, France
| | - Raul Coimbra
- Riverside University Health System Medical Center, Riverside, CA, USA
| | - Zsolt J Balogh
- Department of Traumatology, John Hunter Hospital and University of Newcastle, Newcastle, NSW, Australia
| | - Elie Chouillard
- General Surgery Department, American Hospital of Paris, Paris, France
| | | | | | - Salomone Di Saverio
- General Surgery Unit, Madonna del Soccorso Hospital, AST Ascoli Piceno, San Benedetto del Tronto, Italy
| | - Giovanna Di Meo
- Department of Precision and Regenerative Medicine and Ionian Area, Unit of Academic General Surgery, University of Bari "A. Moro", Bari, Italy
| | - Arda Isik
- Istanbul Medeniyet University, Istanbul, Turkey
| | - Ari Leppäniemi
- Division of Emergency Surgery, Helsinki University Hospital and University of Helsinki, Helsinki, Finland
| | - Andrey Litvin
- Department of Surgical Diseases No. 3, Gomel State Medical University, University Clinic, Gomel, Belarus
| | - Ernest E Moore
- Ernest E Moore Shock Trauma Center at Denver Health, University of Colorado, Denver, CO, USA
| | - Alessandro Pasculli
- Department of Precision and Regenerative Medicine and Ionian Area, Unit of Academic General Surgery, University of Bari "A. Moro", Bari, Italy
| | - Massimo Sartelli
- Department of General Surgery, Macerata Hospital, Macerata, Italy
| | - Mauro Podda
- Department of Surgical Science, Unit of Emergency Surgery, University of Cagliari, Cagliari, Italy
| | - Mario Testini
- Department of Precision and Regenerative Medicine and Ionian Area, Unit of Academic General Surgery, University of Bari "A. Moro", Bari, Italy
| | - Imtiaz Wani
- Department of Surgery, Government Gousia Hospital, DHS, Srinagar, India
| | - Boris Sakakushev
- General Surgery Department, Medical University, University Hospital St George, Plovdiv, Bulgaria
| | - Vishal G Shelat
- Department of General Surgery, Tan Tock Seng Hospital, Novena, Singapore
| | - Dieter Weber
- Department of General Surgery, Royal Perth Hospital & The University of Western Australia, Perth, Australia
| | - Joseph M Galante
- UC Davis Health, Hospital Clinical Care Services, University of California, Davis, USA
| | - Luca Ansaloni
- Department of General Surgery, University of Pavia, Pavia, Italy
| | - Vanni Agnoletti
- Level 1 Trauma Center, Bufalini Hospital, AUSL Romagna, Cesena, Italy
| | - Jean-Marc Regimbeau
- Service de Chirurgie Digestive du CHU d'Amiens, CHU Sud, Centre Hospitalier Universitaire Amiens-Picardie Site Sud, 80054, Amiens, France
| | - Gianluca Garulli
- Department of Emergency and General Minimally Invasive Surgery, Infermi Hospital, AUSL Romagna, Rimini, Italy
| | - Andrew L Kirkpatrick
- Departments of Surgery and Critical Care Medicine, University of Calgary, Foothills Medical Centre, Calgary, AB, Canada
| | - Walter L Biffl
- Division of Trauma/Acute Care Surgery, Scripps Clinic Medical Group, La Jolla, CA, USA
| | - Fausto Catena
- Department of General and Emergency Surgery, Bufalini Hospital-Level 1 Trauma Center, AUSL Romagna, Cesena, Italy
- Alma Mater Studiorum, University of Bologna, Bologna, Italy
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Kurdi F, Kurdi Y, Reshetov IV. Applications of Indocyanine Green in Breast Cancer for Sentinel Lymph Node Mapping: Protocol for a Scoping Review. JMIRX MED 2025; 6:e66213. [PMID: 39763187 PMCID: PMC11728196 DOI: 10.2196/66213] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/06/2024] [Revised: 10/20/2024] [Accepted: 10/21/2024] [Indexed: 01/15/2025]
Abstract
intro Breast cancer is the leading cause of morbidity and mortality worldwide. Accurate sentinel lymph node (SLN) mapping is crucial for staging and treatment planning in early-stage breast cancer. Indocyanine green (ICG) has emerged as a promising agent for fluorescence imaging in SLN mapping. However, comprehensive assessment of its clinical utility, including accuracy and adverse effects, remains limited. This scoping review aims to consolidate evidence on the use of ICG in breast cancer SLN mapping. Objective The objective of this scoping review is to evaluate the current literature on the use of ICG in SLN mapping for patients with breast cancer. This review aims to assess the accuracy, efficacy, and safety of ICG in this context and to identify gaps in the existing research. The outcomes will contribute to the development of further research as part of a PhD project. Methods Five electronic databases will be searched (PubMed, Embase, MEDLINE, Web of Science, and Scopus) using search strategies developed in consultation with an academic supervisor. The search strategy is set to human studies published in English within the last 11 years. All retrieved citations will be imported to Zotero and then uploaded to Covidence for the screening of titles, abstracts, and full text according to prespecified inclusion criteria. Patients with early-stage breast cancer (T1 and T2), selected T3 cases where the SLN biopsy is accurate, and those with clinically node-negative breast cancer will be included. The intervention criterion includes studies using ICG for SLN mapping and studies on the assessment of fluorescence imaging cameras. Citations meeting the inclusion criteria for full-text review will have their data extracted by 2 independent reviewers, with disagreements resolved by discussion. A data extraction tool will be developed to capture full details about the participants, concept, and context, and findings relevant to the scoping review will be summarized. Results The preliminary search began in December 2023. As of September 2024, papers have been screened and data are currently being extracted. Out of the 2130 references initially imported, 126 studies met the inclusion criteria after screening. The scoping review is expected to be published in January 2025. Conclusions Although ICG technology has been used for SLN mapping in patients with breast cancer, initial searches in 2022 revealed limited data on this technique's feasibility, safety, and effectiveness. At that time, preliminary search of Scopus, MEDLINE, Embase, and PubMed identified no current or forthcoming systematic reviews or scoping reviews on the topic. However, recent searches indicate a substantial increase in research and reviews, reflecting a growing interest and evidence in this area.
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Affiliation(s)
- Feryal Kurdi
- Department of Oncology, Radiotherapy and Plastic and Reconstructive Surgery, Sechenov University, Bolshaya Pirogovskaya, 6c1, Moscow, 119021, Russian Federation, 7 9013488810
| | - Yahya Kurdi
- Department of Oncology, Radiotherapy and Plastic and Reconstructive Surgery, Sechenov University, Bolshaya Pirogovskaya, 6c1, Moscow, 119021, Russian Federation, 7 9013488810
| | - Igor Vladimirovich Reshetov
- Department of Oncology, Radiotherapy and Plastic and Reconstructive Surgery, Sechenov University, Bolshaya Pirogovskaya, 6c1, Moscow, 119021, Russian Federation, 7 9013488810
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Zhao H, Koyanagi K, Ninomiya Y, Kazuno A, Yamamoto M, Shoji Y, Yatabe K, Kanamori K, Tajima K, Mori M. Modification of the lesser curvature incision line enhanced gastric conduit perfusion as determined by indocyanine green fluorescence imaging and decreased the incidence of anastomotic leakage following esophagectomy. Esophagus 2025; 22:68-76. [PMID: 39304552 PMCID: PMC11717851 DOI: 10.1007/s10388-024-01089-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/08/2024] [Accepted: 09/02/2024] [Indexed: 09/22/2024]
Abstract
AIM This study aimed to investigate the effectiveness of a modified incision line on the lesser curvature for gastric conduit formation during esophagectomy in enhancing the perfusion of gastric conduit as determined by indocyanine green fluorescence imaging and reducing the incidence of anastomotic leakage. METHODS A total of 272 patients who underwent esophagectomy at our institute between 2014 and 2022 were enrolled in this study. These patients were divided based on two different types of cutlines on the lesser curvature: conventional group (n = 141) following the traditional cutline and modified group (n = 131) adopting a modified cutline. Gastric conduit perfusion was assessed by ICG fluorescence imaging, and clinical outcomes after esophagectomy were evaluated. RESULTS The distance from the pylorus to the cutline was significantly longer in the modified group compared with the conventional group (median: 9.0 cm vs. 5.0 cm, p < 0.001). The blood flow speed in the gastric conduit wall was significantly higher in the modified group than that in the conventional group (median: 2.81 cm/s vs. 2.54 cm/s, p = 0.001). Furthermore, anastomotic leakage was significantly lower (p = 0.024) and hospital stay was significantly shorter (p < 0.001) in the modified group compared with the conventional group. Multivariate analysis identified blood flow speed in the gastric conduit wall as the only variable significantly associated with anastomotic leakage. CONCLUSIONS ICG fluorescence imaging is a feasible, reliable method for the assessment of gastric conduit perfusion. Modified lesser curvature cutline could enhance gastric conduit perfusion, promote blood circulation around the anastomotic site, and reduce the risk of anastomotic leakage after esophagectomy.
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Affiliation(s)
- Hongbo Zhao
- Department of Gastroenterological Surgery, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa, 259-1193, Japan
- Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital and Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen, China
| | - Kazuo Koyanagi
- Department of Gastroenterological Surgery, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa, 259-1193, Japan.
| | - Yamato Ninomiya
- Department of Gastroenterological Surgery, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa, 259-1193, Japan
| | - Akihito Kazuno
- Department of Gastroenterological Surgery, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa, 259-1193, Japan
| | - Miho Yamamoto
- Department of Gastroenterological Surgery, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa, 259-1193, Japan
| | - Yoshiaki Shoji
- Department of Gastroenterological Surgery, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa, 259-1193, Japan
| | - Kentaro Yatabe
- Department of Gastroenterological Surgery, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa, 259-1193, Japan
| | - Kohei Kanamori
- Department of Gastroenterological Surgery, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa, 259-1193, Japan
| | - Kohei Tajima
- Department of Gastroenterological Surgery, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa, 259-1193, Japan
| | - Masaki Mori
- Department of Gastroenterological Surgery, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa, 259-1193, Japan
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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] [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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Wang GR, Zhong NN, Cao LM, Liu XH, Li ZZ, Xiao Y, Zhou K, Yu YF, Liu B, Bu LL. Lymph nodes in oral squamous cell carcinoma: a comprehensive anatomical perspective. Clin Exp Metastasis 2024; 41:877-890. [PMID: 39377834 DOI: 10.1007/s10585-024-10317-y] [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: 06/21/2024] [Accepted: 09/25/2024] [Indexed: 10/09/2024]
Abstract
Oral squamous cell carcinoma (OSCC) often exhibits a propensity for metastasis to lymph nodes (LNs), significantly influencing prognosis. Neck dissection (ND) is an important part in the treatment of OSCC. Variations in the preference for and pathways of lymph node metastasis (LNM) in different regions of the oral cavity have been observed. Currently, there is a lack of sufficient emphasis on the anatomical perspectives of LNM and ND. This review elucidates the lymphatic system of the maxillofacial regions from an anatomical standpoint, details the distribution of the sentinel LNs across different subsites, and summarizes the various classifications of the cervical LNs. Additionally, we elaborate on the methods used to study the lymphatic system, particularly imaging techniques. Furthermore, we investigate the pathways of cervical LNM and evaluate the efficacy of ND from an anatomical viewpoint. The overall objective of this review is to provide essential anatomical knowledge for managing LNs in OSCC, in the hope of providing patients with effective treatment modalities to enhance their quality of life.
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Affiliation(s)
- Guang-Rui Wang
- State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan, 430079, China
| | - Nian-Nian Zhong
- State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan, 430079, China
| | - Lei-Ming Cao
- State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan, 430079, China
| | - Xuan-Hao Liu
- State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan, 430079, China
| | - Zi-Zhan Li
- State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan, 430079, China
| | - Yao Xiao
- State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan, 430079, China
| | - Kan Zhou
- State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan, 430079, China
| | - Yi-Fu Yu
- State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan, 430079, China
| | - Bing Liu
- State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan, 430079, China.
- Department of Oral & Maxillofacial - Head Neck Oncology, School & Hospital of Stomatology, Wuhan University, Wuhan, 430079, China.
| | - Lin-Lin Bu
- State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan, 430079, China.
- Department of Oral & Maxillofacial - Head Neck Oncology, School & Hospital of Stomatology, Wuhan University, Wuhan, 430079, China.
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Petusseau AF, Ochoa M, Reed M, Doyley MM, Hasan T, Bruza P, Pogue BW. Pressure-enhanced sensing of tissue oxygenation via endogenous porphyrin: Implications for dynamic visualization of cancer in surgery. Proc Natl Acad Sci U S A 2024; 121:e2405628121. [PMID: 39141355 PMCID: PMC11348300 DOI: 10.1073/pnas.2405628121] [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: 03/18/2024] [Accepted: 06/21/2024] [Indexed: 08/15/2024] Open
Abstract
Fluorescence guidance is routinely used in surgery to enhance perfusion contrast in multiple types of diseases. Pressure-enhanced sensing of tissue oxygenation (PRESTO) via fluorescence is a technique extensively analyzed here, that uses an FDA-approved human precursor molecule, 5-aminolevulinic acid (ALA), to stimulate a unique delayed fluorescence signal that is representative of tissue hypoxia. The ALA precontrast agent is metabolized in most tissues into a red fluorescent molecule, protoporphyrin IX (PpIX), which has both prompt fluorescence, indicative of the concentration, and a delayed fluorescence, that is amplified in low tissue oxygen situations. Applied pressure from palpation induces transient capillary stasis and a resulting transient PRESTO contrast, dominant when there is near hypoxia. This study examined the kinetics and behavior of this effect in both normal and tumor tissues, with a prolonged high PRESTO contrast (contrast to background of 7.3) across 5 tumor models, due to sluggish capillaries and inhibited vasodynamics. This tissue function imaging approach is a fundamentally unique tool for real-time palpation-induced tissue response in vivo, relevant for chronic hypoxia, such as vascular diseases or oncologic surgery.
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Affiliation(s)
| | - Marien Ochoa
- Department of Medical Physics, University of Wisconsin-Madison, Madison, WI53705
| | - Matthew Reed
- Department of Medical Physics, University of Wisconsin-Madison, Madison, WI53705
| | - Marvin M. Doyley
- Department of Electrical and Computer Engineering, University of Rochester, Rochester, NY14627
| | - Tayyaba Hasan
- Wellman Center for Photomedicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA02114
| | - Petr Bruza
- Thayer School of Engineering, Dartmouth College, Hanover, NH03755
| | - Brian W. Pogue
- Thayer School of Engineering, Dartmouth College, Hanover, NH03755
- Department of Medical Physics, University of Wisconsin-Madison, Madison, WI53705
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Takahashi M, Fujishiro J, Nomura S, Harada M, Hinoki A, Arake M, Ozeki E, Hara I, Satoh A, Tainaka T, Uchida HO, Morimoto Y. DDS-type near-infrared light absorber enables deeper lesion treatment in laser photothermal therapy while avoiding damage to surrounding organs. Front Bioeng Biotechnol 2024; 12:1444107. [PMID: 39211012 PMCID: PMC11357940 DOI: 10.3389/fbioe.2024.1444107] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2024] [Accepted: 07/30/2024] [Indexed: 09/04/2024] Open
Abstract
The efficacy of drug delivery system (DDS)-type near-infrared (NIR) absorbing agents in enhancing laser photothermal therapy is widely acknowledged. Despite the acknowledged efficacy, the therapeutic advantages of photothermal therapy using DDS-type NIR-absorbing agents over simple photothermal therapy without such agents have not been fully elucidated. This study was designed to investigate two primary objectives: firstly, the ability of DDS-type NIR-absorbing agents to induce cell death at greater depths within tumors, and secondly, their capacity to minimize collateral damage to adjacent healthy organs. To investigate these objectives, we employed a combination of indocyanine green lactosome-a DDS-type NIR-absorbing agent-and a precision-controlled laser hyperthermia system. An orthotopic neuroblastoma tumor model was used to closely simulate clinical conditions. The findings revealed that photothermal therapy using the DDS-type NIR-absorbing agent not only facilitates deeper penetration of cell death within tumors but also significantly mitigates thermal damage to surrounding healthy tissues, when compared to simple phototherapy without the agent. Furthermore, the combined treatment significantly prolonged the survival periods of the animals involved. This study is the first to analyze these therapeutic efficacies using quantitative data from an orthotopic tumor animal model and substantiated the potential of DDS-type NIR-absorbing agents to deepen the therapeutic impact of photothermal therapy while safeguarding vital organs, thereby enhancing overall treatment outcomes.
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Affiliation(s)
- Masataka Takahashi
- Department of Pediatric Surgery, The University of Tokyo, Tokyo, Japan
- Department of Cell Engineering, National Center for Child Health and Development, Tokyo, Japan
| | - Jun Fujishiro
- Department of Pediatric Surgery, The University of Tokyo, Tokyo, Japan
| | - Shinsuke Nomura
- Department of Surgery, National Defense Medical College, Tokorozawa, Japan
| | - Manabu Harada
- Department of Surgery, National Defense Medical College, Tokorozawa, Japan
| | - Akinari Hinoki
- Department of Pediatric Surgery, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan
| | - Masashi Arake
- Department of Physiology, National Defense Medical College, Tokorozawa, Japan
| | - Eiichi Ozeki
- Technology Research Laboratory, Shimadzu Corporation, Kyoto, Japan
| | - Isao Hara
- Technology Research Laboratory, Shimadzu Corporation, Kyoto, Japan
| | - Ayano Satoh
- Department of Applied Chemistry and Biotechnology, Faculty of Engineering, Okayama University, Okayama, Japan
| | - Takahisa Tainaka
- Department of Pediatric Surgery, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan
| | - Hiro-o Uchida
- Department of Pediatric Surgery, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan
| | - Yuji Morimoto
- Department of Physiology, National Defense Medical College, Tokorozawa, Japan
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Wang S, Zhang R, Li X, Chen Y, Zhu L, Yang B, Wang J, Du YH, Liu J, Ye TT, Wang S. "Rigid-Flexible" Dual-Ferrocene Chimeric Nanonetwork for Simultaneous Tumor-Targeted Tracing and Photothermal/Photodynamic Therapy. ACS APPLIED MATERIALS & INTERFACES 2024; 16:36142-36156. [PMID: 38968001 DOI: 10.1021/acsami.4c06437] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 07/07/2024]
Abstract
There is an urgent need to develop phototherapeutic agents with imaging capabilities to assess the treatment process and efficacy in real-time during cancer phototherapy for precision cancer therapy. The safe near-infrared (NIR) fluorescent dyes have garnered significant attention and are desirable for theranostics agents. However, until now, achieving excellent photostability and fluorescence (FL) imaging capability in aggregation-caused quenching (ACQ) dyes remains a big challenge. Here, for the only FDA-approved NIR dye, indocyanine green (ICG), we developed a dual-ferrocene (Fc) chimeric nanonetwork ICG@HFFC based on the rigid-flexible strategy through one-step self-assembly, which uses rigid Fc-modified hyaluronic acid (HA) copolymer (HA-Fc) and flexible octadecylamine (ODA) bonded Fc (Fc-C18) as the delivery system. HA-Fc reserved the ability of HA to target the CD44 receptor of the tumor cell surface, and the dual-Fc region provided a rigid space for securely binding ICG through metal-ligand interaction and π-π conjugation, ensuring excellent photostability. Additionally, the alkyl chain provided flexible confinement for the remaining ICG through hydrophobic forces, preserving its FL. Thereby, a balance is achieved between outstanding photostability and FL imaging capability. In vitro studies showed improved photobleaching resistance, enhanced FL stability, and increased singlet oxygen (1O2) production efficiency in ICG@HFFC. Further in vivo results display that ICG@HFFC had good tumor tracing ability and significant tumor inhibition which also exhibited good biocompatibility.. Therefore, ICG@HFFC provides an encouraging strategy to realize simultaneous enhanced tumor tracing and photothermal/photodynamic therapy (PTT/PDT) and offers a novel approach to address the limitations of ACQ dyes.
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Affiliation(s)
- Sixue Wang
- School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, P. R. China
| | - Rui Zhang
- School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, P. R. China
| | - Xianqiang Li
- School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, P. R. China
| | - Yan Chen
- School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, P. R. China
| | - Lili Zhu
- School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, P. R. China
| | - Boyang Yang
- School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, P. R. China
| | - Jiale Wang
- School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, P. R. China
| | - Yu Hao Du
- School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, P. R. China
| | - Jun Liu
- Wuya College of Innovation, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, P. R. China
| | - Tian Tian Ye
- School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, P. R. China
| | - Shujun Wang
- School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, P. R. China
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9
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Yuda M, Takahashi N, Takano Y, Takeshita K, Fujisaki M, Toya N, Yano F, Eto K. Appropriate concentration setting for the intraoperative administration of indocyanine green for fluorescence imaging to identify the sentinel lymph node in early gastric cancer: a clinical pilot study. Surg Today 2024; 54:801-806. [PMID: 38110619 DOI: 10.1007/s00595-023-02775-w] [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] [Received: 06/28/2023] [Accepted: 10/14/2023] [Indexed: 12/20/2023]
Abstract
PURPOSE Some prospective trials have demonstrated the feasibility of sentinel node (SN) biopsy in gastric cancer (GC) surgery. This study aimed to identify the appropriate concentration settings for the intraoperative injection of indocyanine green (ICG) for SN biopsy. METHODS Before the clinical studies, porcine model experiments explored the optimal concentration of ICG injected intraoperatively. Next, nine GC patients were enrolled in the clinical research. ICG (0.5 ml) was injected intraoperatively into four quadrants of the submucosa around the tumor at various concentrations (0.5, 0.25, and 0.1 mg/ml). The lymphatic basin dissection method was applied to the ICG-positive lymphatic areas. The number and location of the lymphatic basins and positive nodes were recorded intraoperatively. RESULTS In the porcine model, the visibility gradually became clear at an ICG concentration higher than 0.1 mg/ml. In the clinical study, the average number of detected lymphatic basins was 3.3, 1.7, and 1.7, respectively. The mean number of detected SNs was 14.7, 6.7, and 4.0, respectively. CONCLUSION To improve the reproducibility of SN biopsy, it is essential to prepare the correct concentration setting of ICG. Under current conditions in which ICG is injected intraoperatively, a 0.1 mg/ml concentration setting of ICG may be necessary and sufficient for SN identification.
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Affiliation(s)
- Masami Yuda
- Department of Surgery, The Jikei University Kashiwa Hospital, 163-1 Kashiwashita, Kashiwa-Shi, Chiba, 277-8567, Japan
| | - Naoto Takahashi
- Department of Surgery, The Jikei University Kashiwa Hospital, 163-1 Kashiwashita, Kashiwa-Shi, Chiba, 277-8567, Japan.
| | - Yuta Takano
- Department of Surgery, The Jikei University Kashiwa Hospital, 163-1 Kashiwashita, Kashiwa-Shi, Chiba, 277-8567, Japan
| | - Kenji Takeshita
- Department of Surgery, The Jikei University Kashiwa Hospital, 163-1 Kashiwashita, Kashiwa-Shi, Chiba, 277-8567, Japan
| | - Muneharu Fujisaki
- Department of Gastroenterological Surgery, The Jikei University School of Medicine, Tokyo, Japan
| | - Naoki Toya
- Department of Surgery, The Jikei University Kashiwa Hospital, 163-1 Kashiwashita, Kashiwa-Shi, Chiba, 277-8567, Japan
| | - Fumiaki Yano
- Department of Gastroenterological Surgery, The Jikei University School of Medicine, Tokyo, Japan
| | - Ken Eto
- Department of Gastroenterological Surgery, The Jikei University School of Medicine, Tokyo, Japan
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10
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Jia G, Wang J, Wang H, Hu X, Long F, Yuan C, Liang C, Wang F. New insights into red blood cells in tumor precision diagnosis and treatment. NANOSCALE 2024; 16:11863-11878. [PMID: 38841898 DOI: 10.1039/d4nr01454e] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/07/2024]
Abstract
Red blood cells (RBCs), which function as material transporters in organisms, are rich in materials that are exchanged with metabolically active tumor cells. Recent studies have demonstrated that tumor cells can regulate biological changes in RBCs, including influencing differentiation, maturation, and morphology. RBCs play an important role in tumor development and immune regulation. Notably, the novel scientific finding that RBCs absorb fragments of tumor-carrying DNA overturns the conventional wisdom that RBCs do not contain nucleic acids. RBC membranes are excellent biomimetic materials with significant advantages in terms of their biocompatibility, non-immunogenicity, non-specific adsorption resistance, and biodegradability. Therefore, RBCs provide a new research perspective for the development of tumor liquid biopsies, molecular imaging, drug delivery, and other tumor precision diagnosis and treatment technologies.
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Affiliation(s)
- Gaihua Jia
- Department of Laboratory Medicine, Zhongnan Hospital of Wuhan University, Wuhan 430071, China.
| | - Jun Wang
- Department of Laboratory Medicine, Wuhan Children's Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430016, China.
| | - Hu Wang
- Center for Single-Cell Omics and Tumor Liquid Biopsy, Zhongnan Hospital of Wuhan University, Wuhan 430071, China.
| | - Xin Hu
- Department of Laboratory Medicine, Zhongnan Hospital of Wuhan University, Wuhan 430071, China.
| | - Fei Long
- Department of Laboratory Medicine, Zhongnan Hospital of Wuhan University, Wuhan 430071, China.
| | - Chunhui Yuan
- Department of Laboratory Medicine, Wuhan Children's Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430016, China.
- Center for Single-Cell Omics and Tumor Liquid Biopsy, Zhongnan Hospital of Wuhan University, Wuhan 430071, China.
| | - Chen Liang
- Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University, Wuhan 430071, China.
| | - Fubing Wang
- Department of Laboratory Medicine, Zhongnan Hospital of Wuhan University, Wuhan 430071, China.
- Center for Single-Cell Omics and Tumor Liquid Biopsy, Zhongnan Hospital of Wuhan University, Wuhan 430071, China.
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11
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Pang Y, Xue R, Lu W, Chen Z. Intracavity frequency doubling acousto-optic Q-switched high repetition rate high-energy Nd:YLF laser. APPLIED OPTICS 2024; 63:1572-1576. [PMID: 38437370 DOI: 10.1364/ao.516321] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/18/2023] [Accepted: 01/26/2024] [Indexed: 03/06/2024]
Abstract
The ongoing advancement of Ti:sapphire femtosecond laser technology has drawn increasing attention to high repetition rate, high-energy green lasers as ideal pump sources for Ti:sapphire regenerative amplifiers. This study employed a neodymium-doped yttrium lithium fluoride (Nd:YLF) as the gain medium, supplemented with side-pumped laser diodes, acousto-optic Q-switching, and intracavity frequency doubling technologies. The results demonstrated a repetition rate ranging from 1-10 kHz, a pulse width of less than 100 ns, and a single pulse energy exceeding 50 mJ at 527 nm green light output. Furthermore, an operating stability (RMS) of ≤0.15% was maintained for 14 h at a repetition rate of 1 kHz and an output power of 40 W.
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12
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Pogue BW, Zhu TC, Ntziachristos V, Wilson BC, Paulsen KD, Gioux S, Nordstrom R, Pfefer TJ, Tromberg BJ, Wabnitz H, Yodh A, Chen Y, Litorja M. AAPM Task Group Report 311: Guidance for performance evaluation of fluorescence-guided surgery systems. Med Phys 2024; 51:740-771. [PMID: 38054538 DOI: 10.1002/mp.16849] [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] [Received: 01/06/2023] [Revised: 11/02/2023] [Accepted: 11/06/2023] [Indexed: 12/07/2023] Open
Abstract
The last decade has seen a large growth in fluorescence-guided surgery (FGS) imaging and interventions. With the increasing number of clinical specialties implementing FGS, the range of systems with radically different physical designs, image processing approaches, and performance requirements is expanding. This variety of systems makes it nearly impossible to specify uniform performance goals, yet at the same time, utilization of different devices in new clinical procedures and trials indicates some need for common knowledge bases and a quality assessment paradigm to ensure that effective translation and use occurs. It is feasible to identify key fundamental image quality characteristics and corresponding objective test methods that should be determined such that there are consistent conventions across a variety of FGS devices. This report outlines test methods, tissue simulating phantoms and suggested guidelines, as well as personnel needs and professional knowledge bases that can be established. This report frames the issues with guidance and feedback from related societies and agencies having vested interest in the outcome, coming from an independent scientific group formed from academics and international federal agencies for the establishment of these professional guidelines.
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Affiliation(s)
- Brian W Pogue
- Department of Medical Physics, University of Wisconsin-Madison, Madison, Wisconsin, USA
- Thayer School of Engineering, Dartmouth College, Hanover, New Hampshire, USA
| | - Timothy C Zhu
- Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Vasilis Ntziachristos
- Institute for Biological and Medical Imaging, Technical University of Munich, Helmholtz Zentrum Munich, Munich, Germany
| | - Brian C Wilson
- Department of Medical Biophysics, University of Toronto, University Health Network, Toronto, Ontario, Canada
| | - Keith D Paulsen
- Thayer School of Engineering, Dartmouth College, Hanover, New Hampshire, USA
| | - Sylvain Gioux
- Department of Biomedical Engineering, University of Strasbourg, Strasbourg, France
| | - Robert Nordstrom
- Cancer Imaging Program, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA
| | - T Joshua Pfefer
- Center for Devices and Radiological Health, US Food and Drug Administration, Silver Spring, Maryland, USA
| | - Bruce J Tromberg
- National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, Maryland, USA
| | | | - Arjun Yodh
- Department of Physics, University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Yu Chen
- Department of Biomedical Engineering, University of Massachusetts Amherst, Amherst, Massachusetts, USA
| | - Maritoni Litorja
- Sensor Science Division, National Institute of Standards and Technology, Gaithersburg, Maryland, USA
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13
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Akrida I, Michalopoulos NV, Lagadinou M, Papadoliopoulou M, Maroulis I, Mulita F. An Updated Review on the Emerging Role of Indocyanine Green (ICG) as a Sentinel Lymph Node Tracer in Breast Cancer. Cancers (Basel) 2023; 15:5755. [PMID: 38136301 PMCID: PMC10742210 DOI: 10.3390/cancers15245755] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2023] [Revised: 12/04/2023] [Accepted: 12/06/2023] [Indexed: 12/24/2023] Open
Abstract
Sentinel lymph node biopsy (SLNB) has become the standard of care for clinically node-negative breast cancer and has recently been shown by clinical trials to be also feasible for clinically node-positive patients treated with primary systemic therapy. The dual technique using both radioisotope (RI) and blue dye (BD) as tracers for the identification of sentinel lymph nodes is considered the gold standard. However, allergic reactions to blue dye as well as logistics issues related to the use of radioactive agents, have led to research on new sentinel lymph node (SLN) tracers and to the development and introduction of novel techniques in the clinical practice. Indocyanine green (ICG) is a water-soluble dye with fluorescent properties in the near-infrared (NIR) spectrum. ICG has been shown to be safe and effective as a tracer during SLNB for breast cancer and accumulating evidence suggests that ICG is superior to BD and at least comparable to RI alone and to RI combined with BD. Thus, ICG was recently proposed as a reliable SLN tracer in some breast cancer clinical practice guidelines. Nevertheless, there is lack of consensus regarding the optimal role of ICG for SLN mapping. Specifically, it is yet to be determined whether ICG should be used in addition to BD and/or RI, or if ICG could potentially replace these long-established traditional SLN tracers. This article is an updated overview of somerecent studies that compared ICG with BD and/or RI regarding their accuracy and effectiveness during SLNB for breast cancer.
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Affiliation(s)
- Ioanna Akrida
- Department of Surgery, General University Hospital of Patras, 26504 Rio, Greece; (I.A.); (I.M.)
| | - Nikolaos V. Michalopoulos
- 4th Department of Surgery, Attikon University Hospital, Medical School, National and Kapodistrian University of Athens, 1 Rimini Street, Chaidari, 12462 Athens, Greece; (N.V.M.); (M.P.)
| | - Maria Lagadinou
- Department of Internal Medicine, General University Hospital of Patras, 26504 Rio, Greece;
| | - Maria Papadoliopoulou
- 4th Department of Surgery, Attikon University Hospital, Medical School, National and Kapodistrian University of Athens, 1 Rimini Street, Chaidari, 12462 Athens, Greece; (N.V.M.); (M.P.)
| | - Ioannis Maroulis
- Department of Surgery, General University Hospital of Patras, 26504 Rio, Greece; (I.A.); (I.M.)
| | - Francesk Mulita
- Department of Surgery, General University Hospital of Patras, 26504 Rio, Greece; (I.A.); (I.M.)
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14
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Hingsammer L, Schönegg D, Gander T, Lanzer M. Radioactive nanosized colloids and indocyanine green identify the same sentinel lymph nodes in oral squamous cell carcinoma. J Cancer Res Clin Oncol 2023; 149:17223-17229. [PMID: 37801136 PMCID: PMC10657288 DOI: 10.1007/s00432-023-05427-1] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2023] [Accepted: 09/13/2023] [Indexed: 10/07/2023]
Abstract
PURPOSE Near-infrared fluorescence imaging using indocyanine green (ICG) combined with radioactive markers has the potential to improve sentinel lymph-node (SLN) mapping in oral squamous cell carcinoma (OSCC). This study aimed to evaluate the ability of 99mTc and ICG in identifying the sentinel lymph nodes in patients with early stage OSCC. METHODS Data were collected prospectively, and a retrospective analysis of 15 patients with early stage OSCC and a cN0 neck was performed. All patients received peritumoral injection of 99mTc the day before surgery and ICG was administered intraoperatively. Intentionally, the application of the two different tracers were done by two different physicians with varying degrees of experience. The number of identified lymph nodes positive for 99mTc and ICG, the overlap or possible discrepancies of both methods, and the time until fluorescence signals of ICG were detected were noted. RESULTS In all patients, a 100% agreement in sentinel lymph-node identification was achieved, regardless of both the exact location of the peritumoral injection and the experience of the injecting surgeon. Time until ICG accumulation in the sentinel lymph node was consistently found to be between 1 and 3 min. CONCLUSION ICG constitutes a viable and useful addition to 99mTc for intraoperative sentinel lymph-node detection in this study.
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Affiliation(s)
- Lukas Hingsammer
- Medical University of Vienna, Spitalgasse 23, 1090, Vienna, Austria.
- Department of Cranio-Maxillo-Facial and Oral Surgery, University Hospital of Zurich, Rämistrasse 100, 8091, Zurich, Switzerland.
| | - Daphne Schönegg
- Department of Cranio-Maxillo-Facial and Oral Surgery, University Hospital of Zurich, Rämistrasse 100, 8091, Zurich, Switzerland
| | - Thomas Gander
- Department of Cranio-Maxillo-Facial and Oral Surgery, University Hospital of Zurich, Rämistrasse 100, 8091, Zurich, Switzerland
| | - Martin Lanzer
- Department of Cranio-Maxillo-Facial and Oral Surgery, University Hospital of Zurich, Rämistrasse 100, 8091, Zurich, Switzerland
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15
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Izzo S, Molle M, Gesuete FP, De Intinis C, Izzo P, Izzo L, Nicoletti GF. Comparison of Different Techniques for the Assessment of Sentinel Lymph Node Biopsy in Melanoma: A Systematic Review. PLASTIC AND RECONSTRUCTIVE SURGERY-GLOBAL OPEN 2023; 11:e5447. [PMID: 38145154 PMCID: PMC10745233 DOI: 10.1097/gox.0000000000005447] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2023] [Accepted: 10/03/2023] [Indexed: 12/26/2023]
Abstract
Background The gold standard for sentinel lymph node staging in melanoma is the use of the combined technique of radioisotope plus blue dye. New techniques and alternative methods have been proposed, with the promise of achieving comparable efficacy. We then carried out a literature search. Methods We conducted a literature search using the "sentinel lymph node biopsy" and "melanoma" keywords, then selected the case-control studies (the quality of which was assessed using the STROBE criteria). Results Twelve studies of 13,017 were selected, concerning the identification rate of indocyanine green fluorescence and indocyanine green-99mtc-nanocolloid techniques. We have found a comparable identification rate between the various techniques, even if given the small population present for some techniques, the results did not reach statistical significance. Conclusions The use of new techniques in sentinel lymph node detection promises results comparable to the gold standard techniques, but further studies are needed to validate these methods in the context of melanoma surgery.
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Affiliation(s)
- Sara Izzo
- From the Università Degli Studi Della Campania “L. Vanvitelli,” Naples, Italy
| | - Marcello Molle
- From the Università Degli Studi Della Campania “L. Vanvitelli,” Naples, Italy
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16
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Millard M, Bernhard Y, Canilho N, Grandemange S, Parant S, Mourer M, Lassalle HP, Pasc A. Enhanced stability and photothermal efficiency of Indocyanine Green J-aggregates by nanoformulation with Calix[4]arene for photothermal therapy of cancers. Colloids Surf B Biointerfaces 2023; 230:113516. [PMID: 37660516 DOI: 10.1016/j.colsurfb.2023.113516] [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] [Received: 12/07/2022] [Revised: 07/17/2023] [Accepted: 08/13/2023] [Indexed: 09/05/2023]
Abstract
Photothermal therapy (PTT) is a method of growing attention, owing to its controllable process, high efficiency and minimal side effect. Indocyanine Green (ICG) is as Food and Drug Administration (FDA) approved agent that stands on the frontline of further developments of PTT toward clinics. However, the applicability of ICG-mediated PTT is limited by the rapid in vivo clearance and photo-degradation of ICG. To improve those parameters, nanosized ICG-loaded nanoparticles (ICG-J/CX) were fabricated in this study by co-assembly of anionic ICG J-aggregates (ICG-J) with cationic tetraguanidinium calix[4]arene (CX). This very simple approach produces ICG-J/CX with a well-defined nanometer range size and a close to neutral charge. The nanoparticles demonstrate high photothermal conversion efficiency (PCE) and dramatically improved photostability, as compared with ICG. The in vitro cellular uptake and cytotoxicity studies further demonstrated that the ICG-J/CX nanoparticles enhance uptake and photothermal efficiency in comparison with ICG or non-formulated ICG-J, overall demonstrating that ICG-J/CX mediated photothermal therapy have significant potential for attaining cancer treatment.
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Affiliation(s)
- Marie Millard
- Université de Lorraine, CNRS, L2CM UMR 7053, F-54506 Vandoeuvre-lès-Nancy, France; Université de Lorraine, CNRS UMR 7039, CRAN, F-54000 Nancy, France
| | - Yann Bernhard
- Université de Lorraine, CNRS, L2CM UMR 7053, F-54506 Vandoeuvre-lès-Nancy, France
| | - Nadia Canilho
- Université de Lorraine, CNRS, L2CM UMR 7053, F-54506 Vandoeuvre-lès-Nancy, France
| | | | - Stéphane Parant
- Université de Lorraine, CNRS, L2CM UMR 7053, F-54506 Vandoeuvre-lès-Nancy, France
| | - Maxime Mourer
- Université de Lorraine, CNRS, L2CM UMR 7053, F-54506 Vandoeuvre-lès-Nancy, France
| | - Henri-Pierre Lassalle
- Université de Lorraine, CNRS UMR 7039, CRAN, F-54000 Nancy, France; Institut de Cancérologie de Lorraine, Unité de Recherche Translationnelle F-54000 Nancy, France.
| | - Andreea Pasc
- Université de Lorraine, CNRS, L2CM UMR 7053, F-54506 Vandoeuvre-lès-Nancy, France.
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Najafabad BK, Attaran N, Mahmoudi M, Sazgarnia A. Effect of photothermal and photodynamic therapy with cobalt ferrite superparamagnetic nanoparticles loaded with ICG and PpIX on cancer stem cells in MDA-MB-231 and A375 cell lines. Photodiagnosis Photodyn Ther 2023; 43:103648. [PMID: 37315828 DOI: 10.1016/j.pdpdt.2023.103648] [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] [Received: 03/14/2023] [Revised: 05/10/2023] [Accepted: 06/01/2023] [Indexed: 06/16/2023]
Abstract
BACKGROUND Cancer cells are resistant to treatments such as chemotherapy and radiotherapy due to their characteristics such as self-renewal, high proliferation and other resistance mechanisms. To overcome this resistance, we combined a light-based treatment with nanoparticles to get advantage of both PDT and PTT in order to increase efficiency and beater outcome. METHODS AND MATERIAL After synthesis and characterization of CoFe2O4@citric@PEG@ICG@ PpIX NPs, their dark cytotoxicity concentration was determined with MTT assay. Then light-base treatments were performed by two different light source for MDA-MB-231 and A375 cell lines. After treatment, the results were evaluated 48 h and 24 h after treatment by MTT assay and flow cytometry. Among CSCs defined markers, CD44, CD24 and CD133 are the most widely-used markers in CSC research and are also therapeutic targets in cancers. So we used proper antibodies to detect CSCs. Then indexes like ED50, synergism defined to evaluated the treatment. RESULTS ROS production and temperature increase have a direct relationship with exposure time. In both cell lines, the death rate in combinational treatment (PDT/PTT) is higher than single treatment and the amount of cells with CD44+CD24- and CD133+CD44+ markers has decreased. According to the synergism index, conjugated NPs show a high efficiency in use in light-based treatments. This index was higher in cell line MDA-MB-231 than A375. And the ED50 is proof of the high sensitivity of A375 cell line compared to MDA-MB-231 in PDT and PTT. CONCLUSION Conjugated NPs along with combined photothermal and photodynamic therapies may play an important role in eradication CSCs.
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Affiliation(s)
- Bahareh Khalili Najafabad
- Medical Physics Research Center, Mashhad University of Medical Sciences, Mashhad, Iran; Department of Medical Physics, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Neda Attaran
- Department of Medical Nanotechnology, Applied Biophotonics Research Center, Science and Research Branch, Islamic Azad University, Tehran, Iran
| | - Mahmoud Mahmoudi
- Immunology Research Center, Faculty of Medicine, Bu-Ali Research Institute, Mashhad University of Medical Sciences, Mashhad, Iran.
| | - Ameneh Sazgarnia
- Medical Physics Research Center, Mashhad University of Medical Sciences, Mashhad, Iran; Department of Medical Physics, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
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Vreeburg MTA, Azargoshasb S, van Willigen D, Molenaar T, van Oosterom MN, Buckle T, Slof LJ, Klop M, Karakullukcu B, Donswijk M, van der Poel HG, van Leeuwen FWB, Brouwer OR, Rietbergen DDD. Comparison of two hybrid sentinel node tracers: indocyanine green (ICG)- 99mTc-nanocolloid vs. ICG- 99mTc-nanoscan from a nuclear medicine and surgical perspective. Eur J Nucl Med Mol Imaging 2023; 50:2282-2291. [PMID: 36929210 PMCID: PMC10250462 DOI: 10.1007/s00259-023-06157-9] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2022] [Accepted: 02/15/2023] [Indexed: 03/18/2023]
Abstract
BACKGROUND Lymph node (LN) metastasis is a relevant predictor for survival in patients with a.o. penile cancer (PeCa), malignant melanoma. The sentinel node (SN) procedure comprises targeted resection of the first tumour-draining SNs. Here, the hybrid tracer indocyanine green (ICG)-99mTc-nanocolloid has been used for several years to combine optical and nuclear detection. Recently, the resource of the nanocolloid precursor stopped production and the precursor was replaced by a different but chemically comparable colloid, nanoscan. Our aim was to study the performance of ICG-99mTc-nanoscan compared to ICG-99mTc-nanocolloid from a nuclear and surgical perspective. METHODS Twenty-four patients with either PeCa or head-and-neck (H&N) melanoma and scheduled for a SN procedure were included. The initial group (n = 11) received ICG-99mTc-nanocolloid until no longer available; the second group (n = 13) received ICG-99mTc-nanoscan. Tracer uptake was assessed on lymphoscintigraphy and single-photon emission (SPECT). Intraoperatively, SNs were identified using gamma tracing and fluorescence imaging. Ex vivo (back-table) measurements were conducted to quantify the fluorescence emissions. Chemical analysis was performed to compare the ICG assembly on both precursors. RESULTS The mean tracer uptake in the SNs was similar for ICG-99mTc-nanocolloid (2.2 ± 4.3%ID) and ICG-99mTc-nanoscan (1.8 ± 2.6%ID; p = 0.68). 3 SNs (interquartile range (IQR) 3-4) were detected on lymphoscintigraphy in PeCa patients receiving ICG-99mTc-nanoscan compared to 2 SNs (IQR 2-3) in PeCa patients receiving ICG-99mTc-nanocolloid (p = 0.045), no differences were observed in H&N patients. Back-table measurements of resected SNs revealed a lower total fluorescence intensity in the ICG-99mTc-nanoscan group (24*109 arbitrary units (A.U) IQR 1.6*109-14*109 in the ICG-99mTc-nanocolloid group versus 4.6*109 A.U. IQR 2.4*109-42*109 in the ICG-99mTc-nanoscan group, p = 0.0054). This was consistent with a larger degree of "stacked" ICG observed in the nanoscan formulation. No tracer-related adverse events were reported. CONCLUSIONS Based on this retrospective analysis, we can conclude that ICG-99mTc-nanoscan has similar capacity for SN identification as ICG-99mTc-nanocolloid and can safely be implemented in SN procedures.
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Affiliation(s)
- Manon T A Vreeburg
- Department of Urology, The Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands
- Interventional Molecular Imaging Laboratory, Department of Radiology, Leiden University Medical Hospital, Leiden, The Netherlands
| | - Samaneh Azargoshasb
- Department of Urology, The Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands
- Interventional Molecular Imaging Laboratory, Department of Radiology, Leiden University Medical Hospital, Leiden, The Netherlands
| | - Danny van Willigen
- Interventional Molecular Imaging Laboratory, Department of Radiology, Leiden University Medical Hospital, Leiden, The Netherlands
| | - Tom Molenaar
- Interventional Molecular Imaging Laboratory, Department of Radiology, Leiden University Medical Hospital, Leiden, The Netherlands
- Radiochemistry Facility, Department of Radiology, Leiden University Medical Hospital, Leiden, The Netherlands
| | - Matthias N van Oosterom
- Department of Urology, The Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands
- Interventional Molecular Imaging Laboratory, Department of Radiology, Leiden University Medical Hospital, Leiden, The Netherlands
| | - Tessa Buckle
- Department of Urology, The Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands
- Interventional Molecular Imaging Laboratory, Department of Radiology, Leiden University Medical Hospital, Leiden, The Netherlands
| | - Leon J Slof
- Department of Urology, The Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands
- Interventional Molecular Imaging Laboratory, Department of Radiology, Leiden University Medical Hospital, Leiden, The Netherlands
- Instrumentele zaken ontwikkeling, facilitair bedrijf, Leiden University Medical Centre, Leiden, The Netherlands
| | - Martin Klop
- Department of Head and Neck Surgery, The Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands
| | - Baris Karakullukcu
- Department of Head and Neck Surgery, The Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands
| | - Maarten Donswijk
- Department of Nuclear Medicine, 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
- Interventional Molecular Imaging Laboratory, Department of Radiology, Leiden University Medical Hospital, Leiden, The Netherlands
| | - Fijs W B van Leeuwen
- Department of Urology, The Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands
- Interventional Molecular Imaging Laboratory, Department of Radiology, Leiden University Medical Hospital, Leiden, The Netherlands
| | - Oscar R Brouwer
- Department of Urology, The Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands
- Interventional Molecular Imaging Laboratory, Department of Radiology, Leiden University Medical Hospital, Leiden, The Netherlands
| | - Daphne D D Rietbergen
- Interventional Molecular Imaging Laboratory, Department of Radiology, Leiden University Medical Hospital, Leiden, The Netherlands.
- Department of Radiology, Section Nuclear Medicine, Leiden University Medical Hospital, Leiden, The Netherlands.
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Reed MS, Ochoa M, Tichauer KM, Weichmann A, Doyley MM, Pogue BW. Mapping estimates of vascular permeability with a clinical indocyanine green fluorescence imaging system in experimental pancreatic adenocarcinoma tumors. JOURNAL OF BIOMEDICAL OPTICS 2023; 28:076001. [PMID: 37457627 PMCID: PMC10344470 DOI: 10.1117/1.jbo.28.7.076001] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 03/20/2023] [Revised: 06/18/2023] [Accepted: 06/22/2023] [Indexed: 07/18/2023]
Abstract
Significance Pancreatic cancer tumors are known to be avascular, but their neovascular capillaries are still chaotic leaky vessels. Capillary permeability could have significant value for therapy assessment, and its quantification might be possible with macroscopic imaging of indocyanine green (ICG) kinetics in tissue. Aim The capacity of using standard fluorescence surgical systems for ICG kinetic imaging as a probe for capillary leakage was evaluated using a clinical surgical fluorescence imaging system, as interpreted through vascular permeability modeling. Approach Xenograft pancreatic adenocarcinoma models were imaged in mice during bolus injection of ICG to capture the kinetics of uptake. Image analysis included ratiometric data, normalization, and match to theoretical modeling. Kinetic data were converted into the extraction fraction of the capillary leakage. Results Pancreatic tumors were usually less fluorescent than the surrounding healthy tissues, but still the rate of tumor perfusion could be assessed to quantify capillary extraction. Model simulations showed that flow kinetics stabilized after about 1 min beyond the initial bolus injection and that the relative extraction fraction model estimates matched the experimental data of normalized uptake within the tissue. The kinetics in the time period of 1 to 2 min post-injection provided optimal differential data between AsPC1 and BxPC3 tumors, although high individual variation exists between tumors. Conclusions ICG kinetic imaging during the initial leakage phase was diagnostic for quantitative vascular permeability within pancreatic tumors. Methods for autogain correction and normalized model-based interpretation allowed for quantification of extraction fraction and difference identification between tumor types in early timepoints.
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Affiliation(s)
- Matthew S. Reed
- University of Wisconsin-Madison, Department of Medical Physics, Madison, Wisconsin, United States
| | - Marien Ochoa
- University of Wisconsin-Madison, Department of Medical Physics, Madison, Wisconsin, United States
| | - Kenneth M. Tichauer
- Illinois Institute of Technology, Department of Biomedical Engineering, Chicago, Illinois, United States
| | - Ashley Weichmann
- University of Wisconsin-Madison, Department of Medical Physics, Madison, Wisconsin, United States
| | - Marvin M. Doyley
- University of Rochester, Department of Electrical and Computer Engineering, Rochester, New York, United States
| | - Brian W. Pogue
- University of Wisconsin-Madison, Department of Medical Physics, Madison, Wisconsin, United States
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Nanoparticles for Lymph Node-Directed Delivery. Pharmaceutics 2023; 15:pharmaceutics15020565. [PMID: 36839887 PMCID: PMC9960358 DOI: 10.3390/pharmaceutics15020565] [Citation(s) in RCA: 17] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2023] [Revised: 02/03/2023] [Accepted: 02/07/2023] [Indexed: 02/10/2023] Open
Abstract
Lymph nodes are organs that control immune cells and provide a major pathway for primary tumors to metastasize. A nanoparticles-based strategy has several advantages that make it suitable for achieving effective lymphatic delivery. First, the size of nanoparticles can be tailored to meet a size range appropriate for lymphatic migration. In addition, functionalized nanoparticles can target cells of interest for delivery of drugs or imaging probes. Existing lymph node contrast agents map all lymph nodes regardless of metastasis status; however, by using nanoparticles, it is possible to selectively target lymphatic metastases. Moreover, using functionalized nanoparticles, it is possible to specifically deliver anticancer drugs to metastatic lymph nodes. In this review, we introduce the use of nanoparticles for lymphatic mapping, in particular highlighting design considerations for detecting metastatic lymph nodes. Furthermore, we assess trends in lymph node-targeting nanoparticles in clinical practice and suggest future directions for lymph node-targeting nanoparticles.
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21
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Pavlov VN, Urmantsev MF, Bakeev MR. Opportunities of ICG-fluorescent imaging of lymph nodes during radical cystectomy in patients with bladder cancer: A review. JOURNAL OF MODERN ONCOLOGY 2023. [DOI: 10.26442/18151434.2022.4.201874] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
Today, the "golden standard" for the treatment of aggressive forms of bladder cancer is radical cystectomy. An important stage is the pelvic lymphadenectomy. This procedure is crucial for staging the tumor process, determining the subsequent treatment tactics and improving the results of surgery. Currently, the concept of a signaling lymph node (LN) is actively developing, which allows reducing the necessary level of dissection of the pelvic LN. Reducing the number of resected LN increases the level of surgical safety of the patient. The leading method of intraoperative visualization of signal LN is the fluorescence of indocyanine green in the near infrared range of the spectrum. The prospects of this diagnostic method for radical cystectomy in patients with bladder cancer determine the vector of future scientific research in this area.
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22
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Miyamoto S, Nakayama M, Kano K, Tsutsumi S, Momiyama K, Matsuki T, Yamashita T. Novel color fluorescence imaging for sentinel lymph node detection in oral and oropharyngeal cancer. Asia Pac J Clin Oncol 2023; 19:250-256. [PMID: 35871767 DOI: 10.1111/ajco.13815] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2021] [Revised: 02/06/2022] [Accepted: 06/18/2022] [Indexed: 01/20/2023]
Abstract
AIM Fluorescence imaging (FI) using indocyanine green (ICG) is a noteworthy alternative technique for sentinel lymph node (SLN) detection without radiation exposure in oral cavity and oropharynx cancer. However, conventional FI is monochrome, so the visibility is limited. This study assessed whether color FI using the HyperEye Medical System (HEMS) is feasible as an alternative for SLN detection. METHODS Patients with previously untreated cT1-2N0 oral or oropharyngeal cancer who were to undergo primary tumor resection and elective neck dissection (END) in our hospital were enrolled from November 2012 to March 2016. The patients underwent SLN detection for biopsy via the HEMS following the injection of ICG solution around the primary lesion before neck dissection. The visibility and the diagnostic accuracy of the imaging were evaluated. RESULTS SLNs were visualized in all eight cases; however, transcutaneous fluorescence detection was not observed in all cases. Utilizing color mode imaging simplified harvest by clearly discriminating SLNs from surrounding structures, while the monochrome mode proved to be more sensitive for detection. Two cases showed occult metastases on both sentinel and regional nodes. The identification and false negative rates were 100% and 0%, respectively. There were no complications incurred due to this method. CONCLUSION Our results suggest that color FI with the HEMS allows for the accurate and safe harvest of SLNs with a preparatory skin incision. Although there is room for improvement of sensitivity, this easy-to-handle procedure might provide the potential to expand the role of the ICG method for SLN detection in head and neck cancer.
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Affiliation(s)
- Shunsuke Miyamoto
- Department of Otorhinolaryngology-Head and Neck Surgery, Kitasato University School of Medicine, Sagamihara, Japan
| | - Meijin Nakayama
- Department of Otorhinolaryngology-Head and Neck Surgery, Kitasato University School of Medicine, Sagamihara, Japan.,Department of Otorhinolaryngology-Head and Neck Surgery, Yokohama City University, Yokohama, Japan
| | - Koichi Kano
- Department of Otorhinolaryngology-Head and Neck Surgery, Kitasato University School of Medicine, Sagamihara, Japan
| | - Shohei Tsutsumi
- Department of Otorhinolaryngology-Head and Neck Surgery, Kitasato University School of Medicine, Sagamihara, Japan
| | - Kaho Momiyama
- Department of Otorhinolaryngology-Head and Neck Surgery, Kitasato University School of Medicine, Sagamihara, Japan
| | - Takashi Matsuki
- Department of Otorhinolaryngology-Head and Neck Surgery, Kitasato University School of Medicine, Sagamihara, Japan
| | - Taku Yamashita
- Department of Otorhinolaryngology-Head and Neck Surgery, Kitasato University School of Medicine, Sagamihara, Japan
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Aghayan S, Yazdanfar A, Seyedjafari E, Noroozian M, Ioana Bordea R, Chiniforush N. Evaluation of indocyanine-mediated photodynamic therapy cytotoxicity in human osteoblast-like cells: an in vitro study. Folia Med (Plovdiv) 2022; 64:932-937. [PMID: 36876572 DOI: 10.3897/folmed.64.e67475] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2021] [Accepted: 09/20/2021] [Indexed: 01/01/2023] Open
Abstract
INTRODUCTION Antimicrobial photodynamic therapy (aPDT) is an adjunctive non-invasive procedure for the management of periodontal tissue infection and deep periodontal pocket decontamination. However, the effects of this procedure on periodontal cells like osteoblasts that play a role in periodontal tissue repair and regeneration is not yet clear.
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Xiong H, Xu Y, Kim B, Rha H, Zhang B, Li M, Yang GF, Kim JS. Photo-controllable biochemistry: Exploiting the photocages in phototherapeutic window. Chem 2022. [DOI: 10.1016/j.chempr.2022.11.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/05/2022]
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25
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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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Bigcas JLM, DeBiase CA, Ho T. Indocyanine Green Angiography as the Principal Design and Perfusion Assessment Tool for the Supraclavicular Artery Island Flap in Head and Neck Reconstruction. Cureus 2022; 14:e29007. [PMID: 36237816 PMCID: PMC9551620 DOI: 10.7759/cureus.29007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/10/2022] [Indexed: 12/05/2022] Open
Abstract
A consecutive case series of supraclavicular artery island flaps was designed using indocyanine green angiography (IcG-A) in head and neck reconstruction to demonstrate its utilization in supraclavicular artery island flap (SCAIF) head and neck reconstruction. IcG-A was used consecutively between April 2014 and July 2015 to evaluate its use in flap design, inset, and intraoperative decision-making in five patients undergoing head and neck reconstruction. Six SCAIFs were harvested in five patients where IcG-A was used as the primary tool for flap design by visually mapping the supraclavicular artery under fluorescence. Each flap was harvested around the mapped course of the artery. Confirmatory Doppler was present in each flap raised with this technique. In all five patients, IcG-A was used to assess flap perfusion after inset. This case series demonstrates IcG-A as another tool for SCAIF design in head and neck reconstruction. The technology provides direct visualization of the pedicle before harvest. It can also be used as an intraoperative tool to visualize the blood supply once the flap is rotated to assess flap perfusion and detect areas that may be compromised, thereby improving flap survival.
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27
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Shinoda K, Suganami A, Moriya Y, Yamashita M, Tanaka T, Suzuki AS, Suito H, Akutsu Y, Saito K, Shinozaki Y, Isojima K, Nakamura N, Miyauchi Y, Shirasawa H, Matsubara H, Okamoto Y, Nakayama T, Tamura Y. Indocyanine green conjugated phototheranostic nanoparticle for photodiagnosis and photodynamic reaciton. Photodiagnosis Photodyn Ther 2022; 39:103041. [PMID: 35914696 DOI: 10.1016/j.pdpdt.2022.103041] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2022] [Revised: 07/20/2022] [Accepted: 07/28/2022] [Indexed: 11/28/2022]
Abstract
BACKGROUND Phototheranostics represents a highly promising paradigm for cancer therapy, although selecting an appropriate optical imager and sensitizer for clinical use remains challenging. METHODS Liposomally formulated phospholipid-conjugated indocyanine green, denoted as LP-iDOPE, was developed as phototheranostic nanoparticle and its cancer imaging-mediated photodynamic reaction, defined as the immune response induced by photodynamic and photothermal effects, was evaluated with a near-infrared (NIR)-light emitting diode (LED) light irradiator. RESULTS Using in vivo NIR fluorescence imaging, we demonstrated that LP-iDOPE was selectively delivered to tumor sites with high accumulation and a long half-life. Following low-intensity NIR-LED light irradiation on the tumor region of LP-iDOPE accumulated, effector CD8+ T cells were activated at the secondary lymphoid organs, migrated, and subsequently released cytokines including interferon-γ and tumor necrosis factor-α, resulting in effective tumor regression. CONCLUSIONS Our anti-cancer strategy based on tumor-specific LP-iDOPE accumulation and low-intensity NIR-LED light irradiation to the tumor regions, i.e., photodynamic reaction, represents a promising approach to noninvasive cancer therapy.
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Affiliation(s)
- Kenta Shinoda
- Department of Immunology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan
| | - Akiko Suganami
- Department of Bioinformatics, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan; Molecular Chirality Research Center, Chiba University, Chiba 263-8522, Japan
| | - Yasumitsu Moriya
- Department of General Thoracic Surgery, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan
| | - Masamichi Yamashita
- Department of Veterinary Clinical Medicine, School of Veterinary Medicine, Tottori University, Tottori 680-8553, Japan
| | - Tsutomu Tanaka
- Department of Veterinary Clinical Medicine, School of Veterinary Medicine, Tottori University, Tottori 680-8553, Japan
| | - Akane S Suzuki
- Department of Immunology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan
| | - Hiroshi Suito
- Department of Frontier Surgery, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan
| | - Yasunori Akutsu
- Department of Frontier Surgery, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan
| | - Kengo Saito
- Department of Molecular Virology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan
| | | | | | | | | | - Hiroshi Shirasawa
- Department of Molecular Virology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan
| | - Hisahiro Matsubara
- Department of Frontier Surgery, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan
| | - Yoshiharu Okamoto
- Department of Veterinary Clinical Medicine, School of Veterinary Medicine, Tottori University, Tottori 680-8553, Japan
| | - Toshinori Nakayama
- Department of Immunology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan
| | - Yutaka Tamura
- Department of Bioinformatics, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan; Molecular Chirality Research Center, Chiba University, Chiba 263-8522, Japan.
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Guo J, Sim SKR, Teo NZ, Ngu JCY. Pitfalls of indocyanine green perfusional assessment in colorectal anastomosis. ANZ J Surg 2022; 92:1602-1605. [PMID: 35950667 DOI: 10.1111/ans.17910] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2022] [Accepted: 07/03/2022] [Indexed: 11/29/2022]
Affiliation(s)
- Jiwei Guo
- Department of General Surgery, Changi General Hospital, Singapore
| | | | - Nan-Zun Teo
- Department of General Surgery, Changi General Hospital, Singapore
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Schädel-Ebner S, Hirsch O, Gladytz T, Gutkelch D, Licha K, Berger J, Grosenick D. 3D-printed tissue-simulating phantoms for near-infrared fluorescence imaging of rheumatoid diseases. JOURNAL OF BIOMEDICAL OPTICS 2022; 27:074702. [PMID: 35711096 PMCID: PMC9201974 DOI: 10.1117/1.jbo.27.7.074702] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 08/26/2021] [Accepted: 05/26/2022] [Indexed: 06/15/2023]
Abstract
SIGNIFICANCE Fluorescence imaging of rheumatoid diseases with indocyanine green (ICG) is an emerging technique with unique potential for diagnosis and therapy. Device characterization, monitoring of the performance, and further developments of the technique require tissue-equivalent fluorescent phantoms of high stability with appropriate anatomical shapes. AIM Our investigations aim at the development of a three-dimensional (3D) printing technique to fabricate hand and finger models with appropriate optical properties in the near-infrared spectral range. These phantoms should have fluorescence properties similar to ICG, and excellent photostability and durability over years. APPROACH We modified a 3D printing methacrylate photopolymer by adding the fluorescent dye Lumogen IR 765 to the raw material. Reduced scattering and absorption coefficients were adjusted to values representative of the human hand by incorporating titanium dioxide powder and black ink. The properties of printed phantoms of various compositions were characterized using UV/Vis and fluorescence spectroscopy, and time-resolved measurements. Photostability and bleaching were investigated with a hand imager. For comparison, several phantoms with ICG as fluorescent dye were printed and characterized as well. RESULTS The spectral properties of Lumogen IR 765 are very similar to those of ICG. By optimizing the concentrations of Lumogen, titanium dioxide, and ink, anatomically shaped hand and vessel models with properties equivalent to in vivo investigations with a fluorescence hand imager could be printed. Phantoms with Lumogen IR 765 had an excellent photostability over up to 4 years. In contrast, phantoms printed with ICG showed significant bleaching and degradation of fluorescence over time. CONCLUSIONS 3D printing of phantoms with Lumogen IR 765 is a promising method for fabricating anatomically shaped fluorescent tissue models of excellent stability with spectral properties similar to ICG. The phantoms are well-suited to monitor the performance of hand imagers. Concepts can easily be transferred to other fluorescence imaging applications of ICG.
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Affiliation(s)
| | - Ole Hirsch
- Hochschule für angewandte Wissenschaft und Kunst Hildesheim/Holzminden/Göttingen (HAWK), Fakultät Ingenieurwissenschaften und Gesundheit, Göttingen, Germany
| | - Thomas Gladytz
- Physikalisch-Technische Bundesanstalt (PTB), Berlin, Germany
- Max-Delbrück-Centrum für Molekulare Medizin in der Helmholtz-Gemeinschaft (MDC), Berlin, Germany
| | - Dirk Gutkelch
- Physikalisch-Technische Bundesanstalt (PTB), Berlin, Germany
| | - Kai Licha
- FEW Chemicals GmbH, Bitterfeld-Wolfen, Germany
| | | | - Dirk Grosenick
- Physikalisch-Technische Bundesanstalt (PTB), Berlin, Germany
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Budner O, Cwalinski T, Skokowski J, Marano L, Resca L, Cwalina N, Kalinowski L, Hoveling R, Roviello F, Polom K. Methylene Blue Near-Infrared Fluorescence Imaging in Breast Cancer Sentinel Node Biopsy. Cancers (Basel) 2022; 14:1817. [PMID: 35406588 PMCID: PMC8997777 DOI: 10.3390/cancers14071817] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2022] [Accepted: 03/31/2022] [Indexed: 01/25/2023] Open
Abstract
INTRODUCTION Fluorescence-based navigation for breast cancer sentinel node biopsy is a novel method that uses indocyanine green as a fluorophore. However, methylene blue (MB) also has some fluorescent properties. This study is the first in a clinical series presenting the possible use of MB as a fluorescent dye for the identification of sentinel nodes in breast sentinel node biopsy. MATERIAL AND METHODS Forty-nine patients with breast cancer who underwent sentinel node biopsy procedures were enrolled in the study. All patients underwent standard simultaneous injection of nanocolloid and MB. We visualized and assessed the sentinel nodes and the lymphatic channels transcutaneously, with and without fluorescence, and calculated the signal-to-background ratio (SBR). We also analyzed the corresponding fluorescence intensity of various dilutions of MB. RESULTS In twenty-three patients (46.9%), the location of the sentinel node, or the end of the lymphatic path, was visible transcutaneously. The median SBR for transcutaneous sentinel node location was 1.69 (range 1.66-4.35). Lymphatic channels were visible under fluorescence in 14 patients (28.6%) prior to visualization by the naked eye, with an average SBR of 2.01 (range 1.14-5.6). The sentinel node was visible under fluorescence in 25 patients (51%). The median SBR for sentinel node visualization with MB fluorescence was 2.54 (range 1.34-6.86). Sentinel nodes were visualized faster under fluorescence during sentinel node preparation. Factors associated with the rate of visualization included diabetes (p = 0.001), neoadjuvant chemotherapy (p = 0.003), and multifocality (p = 0.004). The best fluorescence was obtained using 40 μM (0.0128 mg/mL) MB, but we also observed a clinically relevant dilution range between 20 μM (0.0064 mg/mL) and 100 μM (0.032 mg/mL). CONCLUSIONS For the first time, we propose the clinical usage of MB as a fluorophore for fluorescence-guided sentinel node biopsy in breast cancer patients. The quenching effect of the dye may be the reason for its poor detection rate. Our analysis of different concentrations of MB suggests a need for a detailed clinical analysis to highlight the practical usefulness of the dye.
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Affiliation(s)
- Oliver Budner
- Frauenheilkunde und Geburtshilfe, HELIOS Kliniken Schwerin, Wissmarsche Street 393-397, 19-055 Schwerin, Germany;
| | - Tomasz Cwalinski
- Department of Surgical Oncology, Faculty of Medicine, Medical University of Gdansk, Marii Sklodowskiej-Curie Street 3a, 80-217 Gdansk, Poland; (T.C.); (J.S.)
| | - Jarosław Skokowski
- Department of Surgical Oncology, Faculty of Medicine, Medical University of Gdansk, Marii Sklodowskiej-Curie Street 3a, 80-217 Gdansk, Poland; (T.C.); (J.S.)
- Department of Medical Laboratory Diagnostics–Biobank Fahrenheit BBMRI.pl, Medical University of Gdansk, Debinki Street 7, 80-211 Gdańsk, Poland;
- Biobanking and Biomolecular Resources Research Infrastructure Poland (BBMRI.pl), 80-210 Gdańsk, Poland
| | - Luigi Marano
- Department of Medicine, Surgery and Neurosciences, Unit of General Surgery and Surgical Oncology, University of Siena, Viale Bracci 16, 53-100 Siena, Italy; (L.M.); (L.R.); (F.R.)
| | - Luca Resca
- Department of Medicine, Surgery and Neurosciences, Unit of General Surgery and Surgical Oncology, University of Siena, Viale Bracci 16, 53-100 Siena, Italy; (L.M.); (L.R.); (F.R.)
| | - Natalia Cwalina
- Department of Pediatrics Ascension, St. John Children’s Hospital, Detroit, MI 48236, USA;
| | - Leszek Kalinowski
- Department of Medical Laboratory Diagnostics–Biobank Fahrenheit BBMRI.pl, Medical University of Gdansk, Debinki Street 7, 80-211 Gdańsk, Poland;
- Biobanking and Biomolecular Resources Research Infrastructure Poland (BBMRI.pl), 80-210 Gdańsk, Poland
- BioTechMed/Department of Mechanics of Materials and Structures, Gdansk University of Technology, Gabriela Narutowicza Street 11/12, 80-233 Gdansk, Poland
| | - Richelle Hoveling
- Quest Medical Imagining, Industrieweg 41, 1775 PW Middenmeer, The Netherlands;
| | - Franco Roviello
- Department of Medicine, Surgery and Neurosciences, Unit of General Surgery and Surgical Oncology, University of Siena, Viale Bracci 16, 53-100 Siena, Italy; (L.M.); (L.R.); (F.R.)
| | - Karol Polom
- Department of Surgical Oncology, Faculty of Medicine, Medical University of Gdansk, Marii Sklodowskiej-Curie Street 3a, 80-217 Gdansk, Poland; (T.C.); (J.S.)
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Pang HY, Liang XW, Chen XL, Zhou Q, Zhao LY, Liu K, Zhang WH, Yang K, Chen XZ, Hu JK. Assessment of indocyanine green fluorescence lymphography on lymphadenectomy during minimally invasive gastric cancer surgery: a systematic review and meta-analysis. Surg Endosc 2022; 36:1726-1738. [PMID: 35079880 DOI: 10.1007/s00464-021-08830-2] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2021] [Accepted: 10/19/2021] [Indexed: 02/05/2023]
Abstract
BACKGROUND In recent years, indocyanine green fluorescence lymphography has been introduced for lymphatic mapping in gastric cancer surgery. The aim of this study was to investigate the efficacy of ICGFL in lymph node dissection during minimally invasive surgery for gastric cancer. METHODS A systematic review of electronic databases including PubMed, Embase, Web of Science, the Cochrane Library, and China National Knowledge Infrastructure was performed from the inception to January 2021 for all studies comparing ICGFL with non-ICGFL in GC patients undergoing minimal access gastrectomy. The primary outcome was the total number of harvested lymph nodes. The secondary endpoints were the number of metastatic LNs, operative time, estimated blood loss, and postoperative complications. The registration number of this protocol is PROSPERO CRD42020203443. RESULTS A total of 13 studies including 1882 participants were included. In this meta-analysis, the use of ICGFL was associated with a higher number of harvested LNs (40.33 vs. 33.40; MD = 6.93; 95%CI: 4.28 to 9.58; P < 0.0001; I2 = 86%). No significant difference was found between the ICGFL and control groups in terms of metastatic LNs (2.63 vs. 2.42; MD = 0.21; 95%CI: -0.46 to 0.87; P = 0.54; I2 = 0%). In addition, the use of ICGFL could be safely performed without increasing the operative time (P = 0.49), estimated blood loss (P = 0.26) and postoperative complications (P = 0.54). CONCLUSION The use of ICGFL may be a useful tool facilitating complete lymph node dissection during minimally invasive GC resection. However, more high-quality RCTs with large sample size are needed to validate this issue.
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Affiliation(s)
- Hua-Yang Pang
- Department of Gastrointestinal Surgery and Laboratory of Gastric Cancer, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University and Collaborative Innovation Center for Biotherapy, No. 37 Guo Xue Xiang Street, Chengdu, 610041, Sichuan Province, China
| | - Xian-Wen Liang
- Department of Gastrointestinal Surgery and Laboratory of Gastric Cancer, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University and Collaborative Innovation Center for Biotherapy, No. 37 Guo Xue Xiang Street, Chengdu, 610041, Sichuan Province, China
| | - Xiao-Long Chen
- Department of Gastrointestinal Surgery and Laboratory of Gastric Cancer, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University and Collaborative Innovation Center for Biotherapy, No. 37 Guo Xue Xiang Street, Chengdu, 610041, Sichuan Province, China
| | - Quan Zhou
- West China School of Medicine, Sichuan University, Chengdu, China
| | - Lin-Yong Zhao
- Department of Gastrointestinal Surgery and Laboratory of Gastric Cancer, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University and Collaborative Innovation Center for Biotherapy, No. 37 Guo Xue Xiang Street, Chengdu, 610041, Sichuan Province, China
| | - Kai Liu
- Department of Gastrointestinal Surgery and Laboratory of Gastric Cancer, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University and Collaborative Innovation Center for Biotherapy, No. 37 Guo Xue Xiang Street, Chengdu, 610041, Sichuan Province, China
| | - Wei-Han Zhang
- Department of Gastrointestinal Surgery and Laboratory of Gastric Cancer, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University and Collaborative Innovation Center for Biotherapy, No. 37 Guo Xue Xiang Street, Chengdu, 610041, Sichuan Province, China
| | - Kun Yang
- Department of Gastrointestinal Surgery and Laboratory of Gastric Cancer, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University and Collaborative Innovation Center for Biotherapy, No. 37 Guo Xue Xiang Street, Chengdu, 610041, Sichuan Province, China
| | - Xin-Zu Chen
- Department of Gastrointestinal Surgery and Laboratory of Gastric Cancer, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University and Collaborative Innovation Center for Biotherapy, No. 37 Guo Xue Xiang Street, Chengdu, 610041, Sichuan Province, China
| | - Jian-Kun Hu
- Department of Gastrointestinal Surgery and Laboratory of Gastric Cancer, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University and Collaborative Innovation Center for Biotherapy, No. 37 Guo Xue Xiang Street, Chengdu, 610041, Sichuan Province, China.
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Multispectral Imaging Using Fluorescent Properties of Indocyanine Green and Methylene Blue in Colorectal Surgery-Initial Experience. J Clin Med 2022; 11:jcm11020368. [PMID: 35054062 PMCID: PMC8778329 DOI: 10.3390/jcm11020368] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2021] [Revised: 12/14/2021] [Accepted: 01/05/2022] [Indexed: 02/06/2023] Open
Abstract
Introduction: Image-guided surgery is becoming a new tool in colorectal surgery. Intraoperative visualisation of different structures using fluorophores helps during various steps of operations. In our report, we used two fluorophores—indocyanine green (ICG), and methylene blue (MB)—during different steps of colorectal surgery, using one camera system for two separate near-infrared wavelengths. Material and methods: Twelve patients who underwent complex open or laparoscopic colorectal surgeries were enrolled. Intravenous injections of MB and ICG at different time points were administered. Visualisation of intraoperative ureter position and fluorescent angiography for optimal anastomosis was performed. A retrospective analysis of patients treated in our departments during 2020 was performed, and data about ureter injury and anastomotic site complications were collected. Results: Intraoperative localisation of ureters with MB under fluorescent light was possible in 11 patients. The mean signal-to-background ratio was 1.58 ± 0.71. Fluorescent angiography before performing anastomosis using ICG was successful in all 12 patients, and none required a change in position of the planned colon resection for anastomosis. The median signal-to-background ratios was 1.25 (IQR: 1.22–1.89). Across both centres, iatrogenic injury of the ureter was found in 0.4% of cases, and complications associated with anastomosis was found in 5.5% of cases. Conclusions: Our study showed a substantial opportunity for using two different fluorophores in colorectal surgery, whereby the visualisation of one will not change the possible quantification analysis of the other. Using two separate dyes during one procedure may help in optimisation of the fluorescent properties of both dyes when using them for different applications. Visualisation of different structures by different fluorophores seems to be the future of image-guided surgery, and shows progress in optical technologies used in image-guided surgery.
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Kang B, Lee JH, Lee J, Jung JH, Kim WW, Chu G, Chae Y, Lee SJ, Lee IH, Yang JD, Lee JS, Park HY. Comparative Study Between Radioisotope Uptake and Fluorescence Intensity of Indocyanine Green for Sentinel Lymph Node Biopsy in Breast Cancer. J Breast Cancer 2022; 25:244-252. [PMID: 35775703 PMCID: PMC9250879 DOI: 10.4048/jbc.2022.25.e27] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2021] [Revised: 03/20/2022] [Accepted: 05/22/2022] [Indexed: 11/30/2022] Open
Abstract
Recently, several breast surgeons have reported a new method for sentinel lymph node biopsy (SLNB) by using indocyanine green (ICG) with infrared camera. This study aimed to determine whether the lymph nodes (LNs) with ICG uptake are true SLNs and to assess the reliability of using only ICG for SLNB. Data were prospectively collected between April and September 2021. All palpable LNs were fat-trimmed and ordered from high to low signal of the gamma detector. The degree of radioisotope uptake and brightness of ICG staining of the axillary LNs detected with a fluorescent camera were compared and associated factors were analyzed. Discordance was defined as sentinel LNs (SLNs) showing a single uptake of radioisotope or fluorescence of ICG only, or when the orders of uptake and intensity degree were different between the 2 materials. A total of 79 SLNBs were performed on 78 patients with breast cancer. The breast cancer was classified as cTis-2N0-1. The discordance rate was 14/79 (17.7%) overall and 45/270 (16.7%) of the total retrieved axillary LNs. The first SLNs showed the lowest discordance rate of 6.3%, whereas the second and third SLNs showed higher discordance rates of 27.6% and 60.0%, respectively. There were no associated clinicopathologic factors that affected the discordance between uptake of radioisotope and fluorescence intensity of ICG. The use of ICG alone for SLNB may be insufficient because of the high discordance rates between radioisotopes and ICG uptake. However, the first SLN could be cautiously regarded as a true SLN.
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Affiliation(s)
- Byeongju Kang
- Department of Surgery, Kyungpook National University Chilgok Hospital, School of Medicine, Kyungpook National University, Daegu, Korea
| | - Jong Ho Lee
- Department of Plastic and Reconstructive Surgery, Kyungpook National University Chilgok Hospital, School of Medicine, Kyungpook National University, Daegu, Korea
| | - Jeeyeon Lee
- Department of Surgery, Kyungpook National University Chilgok Hospital, School of Medicine, Kyungpook National University, Daegu, Korea
| | - Jin Hyang Jung
- Department of Surgery, Kyungpook National University Chilgok Hospital, School of Medicine, Kyungpook National University, Daegu, Korea
| | - Wan Wook Kim
- Department of Surgery, Kyungpook National University Chilgok Hospital, School of Medicine, Kyungpook National University, Daegu, Korea
| | - Gyoyeong Chu
- Department of Surgery, Kyungpook National University Chilgok Hospital, School of Medicine, Kyungpook National University, Daegu, Korea
| | - Yeesoo Chae
- Department of Oncology/Hematology, Kyungpook National University Chilgok Hospital, School of Medicine, Kyungpook National University, Daegu, Korea
| | - Soo Jung Lee
- Department of Oncology/Hematology, Kyungpook National University Chilgok Hospital, School of Medicine, Kyungpook National University, Daegu, Korea
| | - In Hee Lee
- Department of Oncology/Hematology, Kyungpook National University Chilgok Hospital, School of Medicine, Kyungpook National University, Daegu, Korea
| | - Jung Dug Yang
- Department of Plastic and Reconstructive Surgery, Kyungpook National University Chilgok Hospital, School of Medicine, Kyungpook National University, Daegu, Korea
| | - Joon Seok Lee
- Department of Plastic and Reconstructive Surgery, Kyungpook National University Chilgok Hospital, School of Medicine, Kyungpook National University, Daegu, Korea
| | - Ho Yong Park
- Department of Surgery, Kyungpook National University Chilgok Hospital, School of Medicine, Kyungpook National University, Daegu, Korea
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Baio R, Intilla O, Di Mauro U, Pane U, Molisso G, Sanseverino R. OUP accepted manuscript. J Surg Case Rep 2022; 2022:rjab614. [PMID: 35355579 PMCID: PMC8963163 DOI: 10.1093/jscr/rjab614] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2021] [Accepted: 12/14/2021] [Indexed: 11/30/2022] Open
Abstract
Near-infrared fluorescence imaging with indocyanine green has emerging applications in urologic surgery. This technology is strongly used in robotic surgery for several ablative and reconstructive procedures. On the contrary, it is not used at all in the urological laparoscopic surgery. To date, bilateral pelvic lymph node dissection represents the most accurate and reliable staging procedure for the detection of lymph node invasion in prostate cancer and bladder cancer. However, it is not devoid of complications. In this field, indocyanine green fluorescence-guided sentinel lymph node identification is an emerging technique, as accurate staging of urologic cancer could be enhanced by an intraoperative lymphatic mapping. Our goal was to show a high spatial resolution, real-time intraoperative imaging technique to recognize the main lymphatic drainage networks, avoiding at same time lymphatic vessel damage. Furthermore, the use of such an imaging system represents an absolute novelty in the field of urological laparoscopy.
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Affiliation(s)
- Raffaele Baio
- Correspondence address. Department of Medicine and Surgery “Scuola Medica Salernitana,” University of Salerno, Salvador Allende Street 43, 84081 Baronissi, Salerno, Italy. E-mail:
| | - Olivier Intilla
- Department of Urology, Umberto I Hospital, Nocera Inferiore, Salerno, Italy
| | - Umberto Di Mauro
- Department of Urology, Umberto I Hospital, Nocera Inferiore, Salerno, Italy
| | - Umberto Pane
- Department of Urology, Umberto I Hospital, Nocera Inferiore, Salerno, Italy
| | - Giovanni Molisso
- Department of Urology, Umberto I Hospital, Nocera Inferiore, Salerno, Italy
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A Pilot Study Evaluating Sentinel Lymph Node Biopsy Using Dual Dye Technique with ICG and Methylene Blue for Early Breast Carcinoma (EBC). Indian J Surg 2021. [DOI: 10.1007/s12262-021-03124-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022] Open
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Clinical Study of Sentinel Lymph Node Detection Using Photodynamic Eye for Abdominal Radical Trachelectomy. Curr Oncol 2021; 28:4709-4720. [PMID: 34898550 PMCID: PMC8628807 DOI: 10.3390/curroncol28060397] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2021] [Revised: 11/01/2021] [Accepted: 11/13/2021] [Indexed: 12/24/2022] Open
Abstract
This study aimed to assess the accuracy of predicting pelvic lymph node status using sentinel lymph node (SLN) biopsy with indocyanine green (ICG) and to examine the outcomes of SLN biopsy-guided abdominal radical trachelectomy (ART). Patients with stage IA2-IB2 cervical cancer from January 2009 to January 2021 were included. ICG was injected before ART and SLNs were identified, excised, and assessed intraoperatively using fast-frozen sections. Systemic pelvic lymphadenectomy was subsequently performed. The SLN detection rate, sensitivity, and false-negative rate were determined. Thirty patients desiring fertility preservation were enrolled, of whom 26 successfully completed ART and four underwent radical hysterectomies because of metastatic primary SLNs. Bilateral SLNs were identified in all patients. The sensitivity, false-negative rate, and negative predictive value were 100%, 7.7%, and 92.3%, respectively. Three (12%) patients were lost to follow-up: two relapsed and one died of tumor progression. Of the nine patients who tried to conceive after surgery, four achieved pregnancy and three delivered healthy live infants. In women with early-stage cervical cancer who desired to conserve fertility, SLN mapping with ICG had a very high detection rate, sensitivity, and low false-negative rate. SLN biopsy-guided ART is a feasible and accurate method for assessing pelvic node status.
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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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Etemadi A, Imani N, Seyed Jafari E, Chiniforush N. In Vitro Effect of Photodynamic Therapy with Indocyanine Green Followed by 660 nm Photobiomodulation Therapy on Fibroblast Viability. Photochem Photobiol 2021; 98:498-503. [PMID: 34553775 DOI: 10.1111/php.13524] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2021] [Accepted: 09/20/2021] [Indexed: 11/29/2022]
Abstract
This in␣vitro study sought to assess the effect of repetitive PBMT on the viability of fibroblasts following aPDT with indocyanine green (ICG). In this in␣vitro experimental study, human gingival fibroblasts (HGFs) were obtained and incubated in a culture medium. After reaching 10 000 cells cm-2 , the cells were divided into five groups of control, aPDT with ICG and 808 nm (energy density of 24 J cm-2 ), PBMT immediately after aPDT, PBMT with 660 nm (energy density of 7.2 J cm-2 ) immediately and 24 h after aPDT and PBMT immediately and 24 and 48 h after aPDT in 48-well plates. Cell viability was evaluated using the methyl thiazolyl tetrazolium (MTT) assay after 1, 4 and 7 days of incubation. Statistical analyses were performed using one-way ANOVA. Cell viability significantly decreased in group 2 (P < 0.002). We observed no significant increase in cell viability at any time point in group 3 (P > 0.05). Cell viability significantly increased in groups 4 and 5 after the first day of incubation (P < 0.000). Emission of 660 nm as PBMT for two and three times along with passage of time would increase the viability of HGFs following aPDT with ICG.
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Affiliation(s)
- Ardavan Etemadi
- Department of Periodontics, Faculty of Dentistry, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
| | - Negar Imani
- Faculty of Dentistry, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
| | | | - Nasim Chiniforush
- Laser Research Center of Dentistry, Dentistry Research Institute, Tehran University of Medical Sciences, Tehran, Iran
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Cosco ED, Lim I, Sletten EM. Photophysical Properties of Indocyanine Green in the Shortwave Infrared Region. CHEMPHOTOCHEM 2021; 5:727-734. [PMID: 34504949 PMCID: PMC8423351 DOI: 10.1002/cptc.202100045] [Citation(s) in RCA: 34] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2021] [Indexed: 02/04/2023]
Abstract
With the growing development of new contrast agents for optical imaging using near-infrared and shortwave infrared (SWIR) wavelengths, it is essential to have consistent bench-marks for emitters in these regions. Indocyanine green (ICG), a ubiquitous and FDA-approved organic dye and optical imaging agent, is commonly employed as a standard for photophysical properties and biological performance for imaging experiments at these wavelengths. Yet, its reported photophysical properties across organic and aqueous solvents vary greatly in the literature, which hinders its ability to be used as a consistent benchmark. Herein, we measure photophysical properties in organic and aqueous solvents using InGaAs detection (~950-1,700 nm), providing particular relevance for SWIR imaging.
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Affiliation(s)
- Emily D Cosco
- Dr. E. D. Cosco, I. Lim, Prof. E. M. Sletten Department of Chemistry and Biochemistry, California NanoSystems Institute, University of California, Los Angeles, 607 Charles E. Young Dr. East, Los Angeles, CA 90095 (USA)
| | - Irene Lim
- Dr. E. D. Cosco, I. Lim, Prof. E. M. Sletten Department of Chemistry and Biochemistry, California NanoSystems Institute, University of California, Los Angeles, 607 Charles E. Young Dr. East, Los Angeles, CA 90095 (USA)
| | - Ellen M Sletten
- Dr. E. D. Cosco, I. Lim, Prof. E. M. Sletten Department of Chemistry and Biochemistry, California NanoSystems Institute, University of California, Los Angeles, 607 Charles E. Young Dr. East, Los Angeles, CA 90095 (USA)
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Olmeda D, Cerezo-Wallis D, Castellano-Sanz E, García-Silva S, Peinado H, Soengas MS. Physiological models for in vivo imaging and targeting the lymphatic system: Nanoparticles and extracellular vesicles. Adv Drug Deliv Rev 2021; 175:113833. [PMID: 34147531 DOI: 10.1016/j.addr.2021.113833] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2021] [Revised: 05/24/2021] [Accepted: 06/11/2021] [Indexed: 02/06/2023]
Abstract
Imaging of the lymphatic vasculature has gained great attention in various fields, not only because lymphatic vessels act as a key draining system in the body, but also for their implication in autoimmune diseases, organ transplant, inflammation and cancer. Thus, neolymphangiogenesis, or the generation of new lymphatics, is typically an early event in the development of multiple tumor types, particularly in aggressive ones such as malignant melanoma. Still, the understanding of how lymphatic endothelial cells get activated at distal (pre)metastatic niches and their impact on therapy is still unclear. Addressing these questions is of particular interest in the case of immune modulators, because endothelial cells may favor or halt inflammatory processes depending on the cellular context. Therefore, there is great interest in visualizing the lymphatic vasculature in vivo. Here, we review imaging tools and mouse models used to analyze the lymphatic vasculature during tumor progression. We also discuss therapeutic approaches based on nanomedicines to target the lymphatic system and the potential use of extracellular vesicles to track and target sentinel lymph nodes. Finally, we summarize main pre-clinical models developed to visualize the lymphatic vasculature in vivo, discussing their applications with a particular focus in metastatic melanoma.
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Affiliation(s)
- David Olmeda
- Melanoma Laboratory, Molecular Oncology Programme, Spanish National Cancer Research Center (CNIO), Madrid, Spain
| | - Daniela Cerezo-Wallis
- Melanoma Laboratory, Molecular Oncology Programme, Spanish National Cancer Research Center (CNIO), Madrid, Spain; Area of Cell & Developmental Biology, Centro Nacional de Investigaciones Cardiovasculares Carlos III, Madrid, 28029, Spain
| | - Elena Castellano-Sanz
- Microenvironment and Metastasis Laboratory, Molecular Oncology Programme, Spanish National Cancer Research Center (CNIO), Madrid, Spain
| | - Susana García-Silva
- Microenvironment and Metastasis Laboratory, Molecular Oncology Programme, Spanish National Cancer Research Center (CNIO), Madrid, Spain
| | - Héctor Peinado
- Microenvironment and Metastasis Laboratory, Molecular Oncology Programme, Spanish National Cancer Research Center (CNIO), Madrid, Spain.
| | - María S Soengas
- Melanoma Laboratory, Molecular Oncology Programme, Spanish National Cancer Research Center (CNIO), Madrid, Spain.
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Zhang Z, Liu C, Akakuru O, Xu W, Wu A, Zhang Y. ICG and Sunitinib-loaded NH2-MOFs for Folate-mediated Hepatocellular Carcinoma Dual-modal Therapy. Chem Res Chin Univ 2021. [DOI: 10.1007/s40242-021-1206-3] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
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Moore C, Borum RM, Mantri Y, Xu M, Fajtová P, O'Donoghue AJ, Jokerst JV. Activatable Carbocyanine Dimers for Photoacoustic and Fluorescent Detection of Protease Activity. ACS Sens 2021; 6:2356-2365. [PMID: 34038103 PMCID: PMC8375416 DOI: 10.1021/acssensors.1c00518] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Activatable contrast agents are of ongoing research interest because they offer low background and high specificity to the imaging target. Engineered sensitivity to protease activity is particularly desirable because proteases are critical biomarkers in cancer, infectious disease, inflammatory disorders, and so forth. Herein, we developed and characterized a set of peptide-linked cyanine conjugates for dual-modal detection of protease activity via photoacoustic (PA) and fluorescence imaging. The peptide-dye conjugates were designed to undergo contact quenching via intramolecular dimerization and contained n dyes (n = 2, 3, or 4) with n - 1 cleavable peptide substrates. The absorption peaks of the conjugates were blue-shifted 50 nm relative to the free dye and had quenched fluorescence. This effect was sensitive to solvent polarity and could be reversed by solvent switching from water to dimethyl sulfoxide. Employing trypsin as a model protease, we observed a 2.5-fold recovery of the peak absorbance, 330-4600-fold fluorescent enhancement, and picomolar detection limits following proteolysis. The dimer probe was further characterized for PA activation. Proteolysis released single dye-peptide fragments that produced a 5-fold PA enhancement through the increased absorption at 680 nm with nanomolar sensitivity to trypsin. The peptide substrate could also be tuned for protease selectivity; as a proof-of-concept, we detected the main protease (Mpro) associated with the viral replication in SARS-CoV-2 infection. Last, the activated probe was imaged subcutaneously in mice and signal was linearly correlated to the cleaved probe. Overall, these results demonstrate a tunable scaffold for the PA molecular imaging of protease activity with potential value in areas such as disease monitoring, tumor imaging, intraoperative imaging, in vitro diagnostics, and point-of-care sensing.
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Affiliation(s)
- Colman Moore
- Department of Nanoengineering, University of California, San Diego, La Jolla, California 92093, United States
| | - Raina M Borum
- Department of Nanoengineering, University of California, San Diego, La Jolla, California 92093, United States
| | - Yash Mantri
- Department of Bioengineering, University of California, San Diego, La Jolla, California 92093, United States
| | - Ming Xu
- Department of Nanoengineering, University of California, San Diego, La Jolla, California 92093, United States
| | - Pavla Fajtová
- Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, California 92093, United States
| | - Anthony J O'Donoghue
- Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, California 92093, United States
| | - Jesse V Jokerst
- Department of Nanoengineering, University of California, San Diego, La Jolla, California 92093, United States
- Materials Science and Engineering Program, University of California, San Diego, La Jolla, California 92093, United States
- Department of Radiology, University of California, San Diego, La Jolla, California 92093, United States
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Baeten IGT, Hoogendam JP, Jeremiasse B, Braat AJAT, Veldhuis WB, Jonges GN, Jürgenliemk-Schulz IM, van Gils CH, Zweemer RP, Gerestein CG. Indocyanine green versus technetium-99m with blue dye for sentinel lymph node detection in early-stage cervical cancer: A systematic review and meta-analysis. CANCER REPORTS (HOBOKEN, N.J.) 2021; 5:e1401. [PMID: 33973745 PMCID: PMC8789613 DOI: 10.1002/cnr2.1401] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/15/2021] [Revised: 03/03/2021] [Accepted: 03/26/2021] [Indexed: 11/30/2022]
Abstract
Background The fluorescent dye indocyanine green (ICG) has emerged as a promising tracer for intraoperative detection of sentinel lymph nodes (SLNs) in early‐stage cervical cancer. Although researchers suggest the SLN detection of ICG is equal to the more conventional combined approach of a radiotracer and blue dye, no consensus has been reached. Aims We aimed to assess the differences in overall and bilateral SLN detection rates with ICG versus the combined approach, the radiotracer technetium‐99m (99mTc) with blue dye. Methods and Results We searched MEDLINE, Embase, and the Cochrane Library from inception to January 1, 2020 and included studies reporting on a comparison of SLN detection with ICG versus 99mTc with blue dye in early‐stage cervical cancer. The overall and bilateral detection rates were pooled with random‐effects meta‐analyses. From 118 studies retrieved seven studies (one cross‐sectional; six retrospective cohorts) were included, encompassing 589 patients. No significant differences were found in the pooled overall SLN detection rate of ICG versus 99mTc with blue dye. Meta‐analyses of all studies showed ICG to result in a higher bilateral SLN detection rate than 99mTc with blue dye; 90.3% (95%CI, 79.8‐100.0%) with ICG versus 73.5% (95%CI, 66.4‐80.6%) with 99mTc with blue dye. This resulted in a significant and clinically relevant risk difference of 16.6% (95%CI, 5.3‐28.0%). With sensitivity analysis, the risk difference of the bilateral detection rate maintained in favor of ICG but was no longer significant (13.2%, 95%CI −0.8‐27.3%). Conclusion ICG appears to provide higher bilateral SLN detection rates compared to 99mTc with blue dye in patients with early‐stage cervical cancer. However, in adherence with the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) guidelines, the quality of evidence is too low to provide strong recommendations and directly omit the combined approach of 99mTc with blue dye.
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Affiliation(s)
- Ilse G T Baeten
- Department of Gynecologic Oncology, Division of Imaging and Oncology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands
| | - Jacob P Hoogendam
- Department of Gynecologic Oncology, Division of Imaging and Oncology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands
| | - Bernadette Jeremiasse
- Department of Surgery, Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands
| | - Arthur J A T Braat
- Department of Radiology and Nuclear Medicine, Division of Imaging and Oncology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands
| | - Wouter B Veldhuis
- Department of Radiology and Nuclear Medicine, Division of Imaging and Oncology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands
| | - Geertruida N Jonges
- Department of Pathology, Division of Laboratory, Pharmacy and Biomedical Genetics, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands
| | - Ina M Jürgenliemk-Schulz
- Department of Radiotherapy, Division of Imaging and Oncology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands
| | - Carla H van Gils
- Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands
| | - Ronald P Zweemer
- Department of Gynecologic Oncology, Division of Imaging and Oncology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands
| | - Cornelis G Gerestein
- Department of Gynecologic Oncology, Division of Imaging and Oncology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands
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Koyanagi K, Ozawa S, Ninomiya Y, Yatabe K, Higuchi T, Yamamoto M, Kanamori K, Tajima K. Indocyanine green fluorescence imaging for evaluating blood flow in the reconstructed conduit after esophageal cancer surgery. Surg Today 2021; 52:369-376. [PMID: 33977382 DOI: 10.1007/s00595-021-02296-4] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2021] [Accepted: 02/27/2021] [Indexed: 11/26/2022]
Abstract
We investigated the effectiveness of indocyanine green (ICG) fluorescence blood flow imaging of the gastric conduit to evaluate anastomotic leakage after esophagectomy. We identified 19 articles using the PRISMA standard for systematic reviews. The more recent studies reported attempts at objective quantification of ICG fluorescence imaging, rather than qualitative assessment. Anastomotic leakage after esophagectomy occurred in 0-33% of the patients who underwent ICG fluorescence imaging. According to the six studies that compared the incidence of anastomotic leakage in the ICG group and the control group, it ranged from 0 to 18.3% in the ICG group and from 0 to 25.2% in the control group, respectively. Overall, the incidence of anastomotic leakage in the ICG group (8.4%) was lower than that in the control group (18.5%). Although the incidence of anastomotic leakage was as high as 43.1% in patients who did not undergo any intraoperative intervention for poor blood flow, it was only 24% in patients who underwent intraoperative intervention. This systematic review revealed that ICG fluorescence imaging may be a crucial adjunctive tool for reducing anastomotic leakage after esophagectomy, suggesting that it should be performed during esophageal reconstruction.
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Affiliation(s)
- Kazuo Koyanagi
- Department of Gastroenterological Surgery, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa, 259-1193, Japan.
| | - Soji Ozawa
- Department of Gastroenterological Surgery, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa, 259-1193, Japan
| | - Yamato Ninomiya
- Department of Gastroenterological Surgery, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa, 259-1193, Japan
| | - Kentaro Yatabe
- Department of Gastroenterological Surgery, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa, 259-1193, Japan
| | - Tadashi Higuchi
- Department of Gastroenterological Surgery, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa, 259-1193, Japan
| | - Miho Yamamoto
- Department of Gastroenterological Surgery, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa, 259-1193, Japan
| | - Kohei Kanamori
- Department of Gastroenterological Surgery, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa, 259-1193, Japan
| | - Kohei Tajima
- Department of Gastroenterological Surgery, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa, 259-1193, Japan
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In Vivo Visualization of the Pericardium Meridian with Fluorescent Dyes. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2021; 2021:5581227. [PMID: 33854554 PMCID: PMC8021474 DOI: 10.1155/2021/5581227] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/15/2021] [Revised: 03/11/2021] [Accepted: 03/18/2021] [Indexed: 12/04/2022]
Abstract
The anatomical basis of acupuncture meridians continues to be enigmatic. Although much attention has been placed on potential correlations with inter/intramuscular fascia or lower electrical impedance, animal studies performed in the past 40 years have shown that tracer dyes—specifically Tc-99m pertechnetate—injected at strategic skin points generate linear migrations closely aligning with acupuncture meridians. To evaluate whether this phenomenon is also observable in humans, we injected two fluorescent dyes—fluorescein sodium and indocyanine green (ICG)—into the dermal layer both at acupuncture points (PC5, PC6, and PC7) and a nonacupoint control. Fifteen healthy volunteers were enrolled in this study. Of the 19 trials of fluorescein injected at PC6, 15 (79%) were associated with slow diffusion of the dye proximally along a path matching closely with the pericardium meridian. Furthermore, the dye emerged and coalesced proximally at exactly acupoint PC3. Injections of ICG at the acupoints PC5, PC6, or PC7 showed a similar trajectory close to the injection site but diverged when migrating proximally, failing converge on acupoint PC3. Injections of either dye at an adjacent PC6-control did not generate any notable linear pathway. Both ultrasound imaging and vein-locating device did not reveal any corresponding vessels (arterial or venous) at the visualized tracer pathway but did demonstrate correlations with intermuscular fascia.
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Association between indocyanine green fluorescence blood flow speed in the gastric conduit wall and superior mesenteric artery calcification: predictive significance for anastomotic leakage after esophagectomy. Esophagus 2021; 18:248-257. [PMID: 33165752 DOI: 10.1007/s10388-020-00797-8] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/28/2020] [Accepted: 10/30/2020] [Indexed: 02/06/2023]
Abstract
BACKGROUND Near-infrared fluorescence using indocyanine green (ICG) has been applied as a real-time navigation tool to observe blood flow in gastric conduit wall after esophagectomy. Atherosclerosis might impair the blood flow of the systemic organs. The aim of the study was to investigate the significances of ICG blood flow speed in the gastric conduit wall and atherosclerotic calcification for the prediction of anastomotic leakage after esophagectomy. METHODS The 109 esophageal cancer patients were prospectively enrolled. ICG fluorescence blood flow speed in the gastric conduit wall and abdominal aortic calcification index (ACI), celiac artery (CA) calcification, and superior mesenteric artery (SMA) calcification were determined. Then, the correlation between ICG fluorescence blood flow speed and anastomotic leakage as well as ACI, CA, and SMA calcification were evaluated. RESULTS Anastomotic leakage occurred in 15 patients. ACI ranged from 0 to 65. CA calcification and SMA calcification were present in 25 and 12 patients. Multivariate analysis demonstrated that ICG fluorescence blood flow speed in the gastric conduit wall of 2.07 cm/s or less (P < 0.001) and SMA calcification (P = 0.026) were the significant independent predictors of anastomotic leakage. Only SMA calcification was significantly associated with ICG fluorescence blood flow speed in the gastric conduit wall (P = 0.026). CONCLUSIONS This study demonstrated that ICG fluorescence blood flow speed in the gastric conduit wall can predict anastomotic leakage after esophagectomy and microvascular perfusion of capillary vessels of the gastric conduit might be impaired by systemic atherosclerosis.
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Pogue BW, Rosenthal EL. Review of successful pathways for regulatory approvals in open-field fluorescence-guided surgery. JOURNAL OF BIOMEDICAL OPTICS 2021; 26:JBO-210023VR. [PMID: 33715318 PMCID: PMC7955139 DOI: 10.1117/1.jbo.26.3.030901] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 01/21/2021] [Accepted: 02/23/2021] [Indexed: 06/12/2023]
Abstract
SIGNIFICANCE The modern use of fluorescence in surgery came iteratively through new devices and pre-existing imaging agents, with indications that were paved via regulatory approvals and device clearances. These events led to a growing set of surgery subspecialty uses. AIM This article outlines the key milestones that initiated commercially marketed systems and agents by highlighting temporal sequences and strategic decisions between them, with the goal of helping to inform future successes. APPROACH A review of successful regulatory approvals and the sequences between them was completed for companies that achieved US Food and Drug Administration (FDA) premarket approval or new drug approvals (NDAs) or device clearances in the fields of fluorescent imaging agents, open surgery imaging devices, and their approved medical indications. RESULTS Angiography agents, indocyanine green and fluorescein, were approved for human use as absorbing dyes, and this use in retinal imaging was the precursor to lateral translation into tissue perfusion imaging in the last two decades with a growing number of devices. Many FDA cleared devices for open fluorescence-guided surgery used the predicate created by the SPY SP2000 system. This first system was 510(k) cleared for angiography imaging with a unique split predicate from x-ray imaging of vasculature and retinal fluorescence angiography. Since that time, the lateral spread of open surgery devices being cleared for new indications has been occurring with a growth of adoption in surgical subspecialties. Growth into new surgical subspecialties has been achieved by leveraging different NDAs and clearances between indications, such that medical uses have broadened over time. CONCLUSIONS Key decisions made by developers to advance specific device clearances and NDAs have been based upon existing optical fluorescent agents. The historical lessons and regulatory trends in newer indications and contrast agents can help the field evolve via successful investment in new systems and applications.
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Affiliation(s)
- Brian W. Pogue
- Thayer School of Engineering at Dartmouth, Center for Imaging Medicine, Hanover, New Hampshire, United States
- Norris Cotton Cancer Center, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire, United States
| | - Eben L. Rosenthal
- Stanford University School of Medicine, Palo Alto, California, United States
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Usability of fluorescence angiography with indocyanine green in the surgical management of penetrating abdominal trauma: A case series. INTERNATIONAL JOURNAL OF SURGERY OPEN 2021. [DOI: 10.1016/j.ijso.2021.02.001] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
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Quinlan ASF, Wainberg SH, Phillips E, Oblak ML. The use of near infrared fluorescence imaging with indocyanine green for vascular visualization in caudal auricular flaps in two cats. Vet Surg 2021; 50:677-686. [PMID: 33491783 DOI: 10.1111/vsu.13577] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2020] [Revised: 11/15/2020] [Accepted: 12/13/2020] [Indexed: 12/18/2022]
Abstract
OBJECTIVES To describe the use of near infrared fluorescence (NIRF) imaging with indocyanine green (ICG) for vascular visualization in two caudal auricular axial pattern flaps (APF). ANIMALS Two client-owned cats with upper eyelid masses. STUDY DESIGN Clinical case report. METHODS Wide surgical excision with enucleation was performed by using a caudal auricular APF for closure. Flap margins and perforating artery location were approximated with anatomical landmarks. The caudal auricular artery origin was then visualized percutaneously by using an exoscope with NIRF camera and light source after a single 2.5-mg dose of IV ICG. Margins were adjusted as required. The flaps were routinely elevated with continued intraoperative visualization of the artery and rotated to complete closure. RESULTS After IV ICG administration, fluorescence was initially visualized after 15 to 18 seconds and remained visible for up to 26 minutes. The achieved visualization led to flap margin adjustments in cat 1. Both cats recovered with minimal flap congestion, excellent hair regrowth, and no long-term complications (>186 days). Cat 1 experienced 100% flap survival. Cat 2 experienced 10% partial thickness flap necrosis, but revision was not required, and the flap was healed at recheck 85 days postoperatively. CONCLUSION The use of ICG for APF vessel visualization prior to and during flap elevation resulted in transcutaneous visualization of the perforating vessel and improved awareness of vessel location intraoperatively. These two cats experienced excellent flap survival without major complications. This report highlights the potential benefits of ICG NIRF in APF for animals undergoing reconstructive surgery.
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Affiliation(s)
- Adam S F Quinlan
- Department of Clinical Studies, Ontario Veterinary College, University of Guelph, Guelph, Ontario, Canada
| | - Shannon H Wainberg
- Department of Clinical Studies, Ontario Veterinary College, University of Guelph, Guelph, Ontario, Canada.,Companion Animal Hospital, Ontario Veterinary College Health Services Centre, Guelph, Ontario, Canada
| | - Erin Phillips
- Companion Animal Hospital, Ontario Veterinary College Health Services Centre, Guelph, Ontario, Canada
| | - Michelle L Oblak
- Department of Clinical Studies, Ontario Veterinary College, University of Guelph, Guelph, Ontario, Canada.,Companion Animal Hospital, Ontario Veterinary College Health Services Centre, Guelph, Ontario, Canada
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Kågedal Å, Margolin G, Held C, da Silva PFN, Piersiala K, Munck-Wikland E, Jacobsson H, Häyry V, Cardell LO. A Novel Sentinel Lymph Node Approach in Oral Squamous Cell Carcinoma. Curr Pharm Des 2021; 26:3834-3839. [PMID: 32053068 DOI: 10.2174/1381612826666200213100750] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2020] [Accepted: 02/08/2020] [Indexed: 12/15/2022]
Abstract
BACKGROUND Occult metastases are common in patients with oral squamous cell carcinoma (OSCC) which is why elective neck dissection, adjuvant radiotherapy or watchful waiting have been treatment options after surgical removal of the primary tumour. Sentinel lymph node biopsy (SLNB) has lately emerged as a novel possibility in treatment planning. OBJECTIVES To establish a reliable and clinically useful protocol for SLNB in staging/elective neck dissection in oral cancer. METHODS Fourteen consecutive patients with T1-T2 N0 oral cancer were enrolled when scheduled for elective neck dissection. RESULTS This study outlines various techniques for improving SLNB in head and neck cancer. After evaluation, a combination of techniques was found to constitute a reliable, clinically adaptable work concept. The suggested procedure starts with the pre-surgical injection of radioactive technetium 99Tcm carried on tilmanocept (Lymphoseek ®) at the tumour site. The radioactivity in the lymph node is then visualized preoperatively with Single Photon Emission Computed Tomography (SPECT/CT). Intraoperatively, indocyanine green (ICG) is injected and a sentinel node is visualized with near-infrared light. To support the sentinel node detection, the surgeon uses a hand-held gamma detection probe. This approach results in a reproducible and reliable detection of sentinel nodes. CONCLUSION This paper presents a novel protocol for the identification of the sentinel node in the head and neck region. The protocol additionally enables the use of flow cytometry analysis of resected lymph nodes.
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Affiliation(s)
- Åsa Kågedal
- Division of ENT Diseases, Department of Clinical Sciences, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden
| | - Gregori Margolin
- Division of ENT Diseases, Department of Clinical Sciences, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden
| | - Cornelia Held
- Department of Medical Radiation Physics and Nuclear Medicine, Karolinska University Hospital, Stockholm, Sweden
| | - Pedro F N da Silva
- Department of Pathology and Cytology, Karolinska University Hospital, Stockholm, Sweden
| | - Krzysztof Piersiala
- Division of ENT Diseases, Department of Clinical Sciences, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden
| | - Eva Munck-Wikland
- Division of ENT Diseases, Department of Clinical Sciences, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden
| | - Hans Jacobsson
- Department of Medical Radiation Physics and Nuclear Medicine, Karolinska University Hospital, Stockholm, Sweden
| | - Valtteri Häyry
- Division of ENT Diseases, Department of Clinical Sciences, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden
| | - Lars O Cardell
- Division of ENT Diseases, Department of Clinical Sciences, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden
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