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Zhong Q, Shang-Guan ZX, Liu ZY, Wu D, Huang ZN, Wang HG, Chen JY, Wu JX, Li P, Xie JW, Zheng CH, Chen QY, Huang CM. Comparison of a submucosal and subserosal approach in ICG-guided laparoscopic lymphadenectomy in gastric cancer patients: long-term outcomes of a phase 3 randomized clinical trial. Int J Surg 2025; 111:2558-2569. [PMID: 39903562 DOI: 10.1097/js9.0000000000002271] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2024] [Accepted: 12/17/2024] [Indexed: 02/06/2025]
Abstract
BACKGROUND Previous studies have demonstrated similar short-term efficacy between subserosal (SSA) and submucosal (SMA) approaches for ICG injection in gastric cancer (GC). This study aims to compare the long-term oncological outcomes of these two injection methods for lymph node (LN) tracing in ICG-guided laparoscopic gastrectomy. MATERIALS AND METHODS This study was a phase 3, open-label, randomized clinical trial (FUGES-019). A total of 266 patients with resectable gastric adenocarcinoma (cT1-4a, N0/ +, M0) were enrolled. We report predefined long-term secondary outcomes, including three-year actual overall survival (OS), three-year actual disease-free survival (DFS), and recurrence patterns. RESULTS Of the 266 participants, 259 patients were included in the per-protocol analysis: 129 in the SSA group and 130 in the SMA group. The actual OS in the SSA group (87.6%) was comparable to that in the SMA group (90.8%, P = 0.41), as were the 3-year actual DFS rates (SSA: 82.9% vs. SMA: 88.5%, log-rank P = 0.19). Per-protocol analysis confirmed the equivalence of the SSA compared with the SMA. The most common type of recurrence was multiple site metastasis (11 of 259[4.24%]), with no differences in recurrence types across cancer stages. Further stratified analysis based on pT, pN staging, tumor size, and BMI showed no significant differences between the two groups. CONCLUSION The 3-year outcomes of the FUGES-019 trial confirm the equivalence of SSA and SMA in ICG-guided laparoscopic lymphadenectomy for GC, supporting the previous short-term findings. The subserosal approach can be recommended for ICG administration based on clinical considerations.
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Affiliation(s)
- Qing Zhong
- Department of Gastric Surgery
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fuzhou, China
| | - Zhi-Xin Shang-Guan
- Department of Gastric Surgery
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fuzhou, China
| | - Zhi-Yu Liu
- Department of Gastric Surgery
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fuzhou, China
| | - Dong Wu
- Department of Gastric Surgery
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fuzhou, China
| | - Ze-Ning Huang
- Department of Gastric Surgery
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fuzhou, China
| | - Hua-Gen Wang
- Department of Gastric Surgery
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fuzhou, China
| | - Jun-Yun Chen
- Department of Gastric Surgery
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fuzhou, China
| | - Jin-Xun Wu
- Department of Pathology, Lian-jiang Country General Hospital, Fuzhou, China
| | - Ping Li
- Department of Gastric Surgery
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fuzhou, China
| | - Jian-Wei Xie
- Department of Gastric Surgery
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fuzhou, China
| | - Chao-Hui Zheng
- Department of Gastric Surgery
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fuzhou, China
| | - Qi-Yue Chen
- Department of Gastric Surgery
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fuzhou, China
| | - Chang-Ming Huang
- Department of Gastric Surgery
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fuzhou, China
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Negrut RL, Cote A, Feder B, Bodog FD, Maghiar AM. Enhanced Lymph Node Detection in Colon Cancer Using Indocyanine Green Fluorescence: A Systematic Review of Studies from 2020 Onwards. J Pers Med 2025; 15:54. [PMID: 39997331 PMCID: PMC11855940 DOI: 10.3390/jpm15020054] [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: 12/06/2024] [Revised: 01/13/2025] [Accepted: 01/27/2025] [Indexed: 02/26/2025] Open
Abstract
Background: Colon cancer is known as one of the most prevalent malignancies in the world. This well-known pathology requires accurate lymph node dissection to achieve effective staging and improved treatment outcomes. Indocyanine green fluorescence imaging has been used as a new technique for enhancing lymph node visualization during surgical intervention. The high rates of local recurrence in colon cancer patients require innovative methods to improve lymphatic mapping and lymph node dissection. This review evaluates the clinical utility and efficacy of ICG imaging in enhancing lymph node accuracy in colon cancer surgery. Materials and methods: A systematic search was conducted in October 2024 (last day of consulting the database was 16 November) across Web of Science, Scopus, and PubMed to identify studies published from 2020 onwards focusing on the use of indocyanine green in colon cancer surgeries. The search terms used were "indocyanine green", "ICG", "fluorescent imaging", "near-infrared imaging", "colon cancer", "colorectal cancer", "colon carcinoma"," colon neoplasms", "surgery", "surgical procedure", "surgical resection", surgical precision". The search followed PRISMA guidelines. The records underwent a two-phase independent screening process conducted by the authors, first based on the title and abstract, followed by full record evaluation. Articles were excluded following certain exclusion criteria: non-human studies; restricted access publications; other publication type than article (review, meta-analysis, questionnaire-based study, case report, etc.), studies focusing on other diseases or studies that focused on the surgical treatment of metastasis from colon cancer; foreign language (non-English); no data of interest for the current review; studies that focused on rectal cancer and that grouped rectal and colon cancer. Data extraction involved both quantitative and qualitative data, such as detection rates, sensitivity, specificity, and other surgical outcomes. Risk of bias was assessed using ROBINS-I, J Joanna Briggs Institute (JBI) Critical Appraisal Checklist, and the Newcastle-Ottawa Scale, depending on study type. The study was not preregistered in PROSPERO. However, to ensure methodological rigor and transparency, it was retrospectively registered in Open Science Framework (OSF). Results: From the 3300 records initially identified, 9 studies were included in this review. Detection rates varied from 55% to 100%, with the highest rate reported in robot-assisted surgeries. The studies showed an improved lymph node detection and lymphatic flow accuracy using ICG fluorescence. Discussion: ICG fluorescence demonstrated substantial benefits, improving staging accuracy and potentially reducing recurrence rates by guiding the lymphadenectomy. The variability observed in detection rates is largely attributed to differences in ICG administration, cancer stage, and surgical approaches. Conclusions: ICG-guided surgery for colon cancer represents a promising advancement, enhancing lymph node detection and staging accuracy. Large-scale randomized trials are essential to establish standardized protocols and validate the efficacy in improving surgical outcomes.
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Affiliation(s)
- Roxana Loriana Negrut
- Department of Medicine, Doctoral School of Biomedical Sciences, Faculty of Medicine and Pharmacy, University of Oradea, 410087 Oradea, Romania; (R.L.N.)
- County Clinical Emergency Hospital Bihor, 410087 Oradea, Romania;
- Department of Surgical Disciplines, Faculty of Medicine and Pharmacy, University of Oradea, 410073 Oradea, Romania
| | - Adrian Cote
- County Clinical Emergency Hospital Bihor, 410087 Oradea, Romania;
- Department of Surgical Disciplines, Faculty of Medicine and Pharmacy, University of Oradea, 410073 Oradea, Romania
| | - Bogdan Feder
- County Clinical Emergency Hospital Bihor, 410087 Oradea, Romania;
- Department of Surgical Disciplines, Faculty of Medicine and Pharmacy, University of Oradea, 410073 Oradea, Romania
| | - Florian Dorel Bodog
- Department of Medicine, Doctoral School of Biomedical Sciences, Faculty of Medicine and Pharmacy, University of Oradea, 410087 Oradea, Romania; (R.L.N.)
- County Clinical Emergency Hospital Bihor, 410087 Oradea, Romania;
- Department of Surgical Disciplines, Faculty of Medicine and Pharmacy, University of Oradea, 410073 Oradea, Romania
| | - Adrian Marius Maghiar
- Department of Medicine, Doctoral School of Biomedical Sciences, Faculty of Medicine and Pharmacy, University of Oradea, 410087 Oradea, Romania; (R.L.N.)
- Department of Surgical Disciplines, Faculty of Medicine and Pharmacy, University of Oradea, 410073 Oradea, Romania
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Tashiro Y, Aoki T, Yasunaga H, Ando S. Indocyanine green dyed gauze-guided minimum invasive surgery for anatomical landmarks and preventing gauze remnants: a pilot study. Langenbecks Arch Surg 2025; 410:40. [PMID: 39812866 DOI: 10.1007/s00423-024-03592-6] [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: 08/24/2024] [Accepted: 12/19/2024] [Indexed: 01/16/2025]
Abstract
PURPOSE We aimed to develop a novel fluorescent surgical gauze dyed with indocyanine green (ICG) to guide surgeons to the target anatomical destination during surgery for real-time navigation and to prevent gauze remnants after surgery. METHODS Surgical gauze was dyed with an aqueous solution of ICG (5.0 × 10- 5 mol L- 1 for Steraze, 1.5 × 10- 4 mol L- 1 for BK-Opeze) at 132 °C (inside pressure: 2.82 atm, 286 kPa) for 15 min using an autoclave, followed by washing with distilled water, drying at room temperature, and sterilizing at 132 °C for 8 min before surgery. Fluorescence (FL) intensity was examined preclinically in the resected specimens using the SPY PHI (Stryker) system. Fourteen patients who underwent laparoscopic- and robotic-assisted gastroenterological surgery at Showa University Hospital were included. RESULTS Fluorescent emission of ICG-dyed gauze was clearly observed through resected specimens with a thickness of approximately 10 mm or more. In a clinical trial, the ICG-dyed gauze was detected earlier with near-infrared (near-IR) FL imaging than under white light during seven cases of laparoscopic and robotic surgery, which could become a precise marker for surgeons to locate the dissection site despite overlaying tissues and nearby disturbances. Additionally, no seepage of ICG from the gauze was observed in all surgical fields. CONCLUSION We successfully developed ICG-dyed gauze exhibiting bright near-IR FL which can guide surgeons to the target anatomical destination and prevent gauze remnants during surgery. This invention would be a powerful support for real-time navigation surgery.
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Affiliation(s)
- Yoshihiko Tashiro
- Division of Gastroenterological and General Surgery, Department of Surgery, School of Medicine, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo, 142-8666, Japan
| | - Takeshi Aoki
- Division of Gastroenterological and General Surgery, Department of Surgery, School of Medicine, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo, 142-8666, Japan.
| | - Hidekazu Yasunaga
- Faculty of Fiber Science and Engineering, Kyoto Lnstitute of Technology, Matsugasaki, Sakyo-ku, Kyoto, 606-8585, Japan
| | - Shinji Ando
- Department of Chemical Science & Engineering, School of Materials and Chemical Technology, Institute of Science Tokyo, 2-12-1 Ookayama, Meguro-ku, Tokyo, 152-8552, Japan.
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ArmTan K, Kim YM. Indocyanine green and near-infrared fluorescence-guided surgery for gastric cancer: a narrative review. JOURNAL OF MINIMALLY INVASIVE SURGERY 2024; 27:185-197. [PMID: 39675751 DOI: 10.7602/jmis.2024.27.4.185] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/27/2024] [Revised: 12/03/2024] [Accepted: 12/04/2024] [Indexed: 12/17/2024]
Abstract
In recent years, indocyanine green (ICG) and near-infrared (NIR) fluorescence-guided surgery has become a versatile and well-researched tool for gastric cancer treatment. Our narrative review aims to explore the applications, benefits, and challenges that are associated with this technique. Initially used to detect sentinel lymph nodes in early gastric cancer, its scope has broadened to include several clinical applications. Its most notable advantages are the ability to guide standard lymphadenectomy, intraoperatively localize tumors and define tumor margins. Despite these advantages, there are still ongoing discussions regarding its accuracy, lack of standardized administration, and oncologic safety in sentinel node navigation surgery. The limited tumor specificity of ICG has been especially put into question, hindering its ability to accurately differentiate between malignant and healthy tissue. With ongoing innovations and its integration into newer endoscopic and robotic systems, ICG-NIR fluorescence imaging shows promise in becoming a standard tool in the surgical treatment of gastric cancer.
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Affiliation(s)
- Kristoff ArmTan
- Division of Gastrointestinal Surgery, Department of Surgery, Severance Hospital, Seoul, Korea
- Department of Surgery, Chong Hua Hospital, Cebu, Philippines
| | - Yoo Min Kim
- Division of Gastrointestinal Surgery, Department of Surgery, Severance Hospital, Seoul, Korea
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Takeshita K, Takahashi N, Takano Y, Toya N, Yano F, Eto K. Utility of near-infrared fluorescent clip for the robot-assisted gastrectomy: Report of 2 cases (case series). Int J Surg Case Rep 2024; 125:110576. [PMID: 39549582 PMCID: PMC11615108 DOI: 10.1016/j.ijscr.2024.110576] [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: 10/04/2024] [Revised: 11/07/2024] [Accepted: 11/08/2024] [Indexed: 11/18/2024] Open
Abstract
INTRODUCTION AND IMPORTANCE The importance of preoperative tumor site marking has increased over the years, as the method of intraoperative primary lesion identification and determination of resection margins is one factor determining whether oncological safety and function-preserving gastrectomy are possible during surgery. We hypothesize that preoperative placement of the near-infrared fluorescent (NIRF) clip, ZEOCLIP FS, near the oral incision line of the gastric tumor will allow for Firefly recognition of the NIRF clip on da Vinci during surgery and easy determination of the tumor location and incision line. Hence, we report on two cases in which the procedure was performed. CASE PRESENTATION Case 1: A 62-year-old woman was diagnosed with early gastric cancer of 35 mm in size located in the greater curvature of the gastric angle and underwent robot-assisted distal gastrectomy. NIRF clips were placed around the negative biopsy-confirmed area on the tumor's oral side by endoscopy on the day before surgery. The clips were identified intraoperatively in Firefly mode, and we performed gastrectomy without using an intraoperative endoscope. Case 2: A 60-year-old man was diagnosed with early gastric cancer 40 mm in size on the anterior wall of the gastric angle and underwent robot-assisted distal gastrectomy. Similarly, NIRF clips were placed around the site of negative biopsy confirmation the day before surgery. NIRF clips were identified, and we performed gastrectomy. CLINICAL DISCUSSION The time taken to mark the gastric resection line after activating the Firefly imaging system was 120 and 154 s, respectively, and intraoperative endoscopy was not required. The advantage of our two-step method is that a surgeon can mark the clips the day before the surgery, even if they are not endoscopists. Increasing the recognition rate of fluorescent clips and preventing their remains are future issues. CONCLUSION Based on the results of the above two cases, ZEOCLIP FS is influential in determining the tumor's location and the resection line.
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Affiliation(s)
- Kenji Takeshita
- Department of Surgery, The Jikei University Kashiwa Hospital, Japan
| | - Naoto Takahashi
- Department of Surgery, The Jikei University Kashiwa Hospital, Japan.
| | - Yuta Takano
- Department of Surgery, The Jikei University Kashiwa Hospital, Japan.
| | - Naoki Toya
- Department of Surgery, The Jikei University Kashiwa Hospital, Japan
| | - Fumiaki Yano
- Department of Surgery, The Jikei University, Tokyo, Japan
| | - Ken Eto
- Department of Surgery, The Jikei University, Tokyo, Japan.
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Sun L, Meng C, Zhang Z, Luo Y, Yang Z, Yao H. Opportunities and challenges of indocyanine green in gastrointestinal cancers for intraoperative and nano-medicine application. Cancer Nanotechnol 2024; 15:12. [DOI: 10.1186/s12645-024-00251-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2023] [Accepted: 01/24/2024] [Indexed: 01/12/2025] Open
Abstract
AbstractThe morbidity and mortality of gastrointestinal tumours remain high worldwide. Surgical resection is currently the most critical radical therapeutic schedule, while postoperative complications and sentinel lymph node (SLN) identification are closely related to the outcome. Indocyanine green (ICG)-mediated fluorescence imaging is increasingly being used in gastrointestinal surgery. It has been embraced by various surgical disciplines as a potential method to improve lymph node detection and enhance surgical field visualization. ICG can passively concentrate in SLN because of enhanced permeation and retention effects. After excitation by near-infrared light devices, SLN can display higher intensity fluorescence, helping visualization for better lymph node dissection. In addition, visual assessment of intestinal blood flow through ICG may reduce the incidence of anastomotic leakage. Although it has good clinical application, ICG-imaging still faces some problems, such as a higher false-negative rate, poorly targeted biodistribution, and lower fluorescence contrast, due to the lack of active tumour targeting. Thus, different ICG-coupled nanoparticles with inherent characteristics or functional modification-enhanced SLN identification features for gastrointestinal cancers bring benefit through active tumour targeting, superior tumour-background ratio, and high resolution. Nano-ICG combined with potential substances, including enhanced imaging contrast and/or combination therapy (chemotherapy, targeted therapy, immunotherapy, etc.), have been packaged and accumulated in the tumour area through active targeting for multimodal imaging and treatment. In this review, we outline the intraoperative application and possible future nanodirections of ICG in gastrointestinal cancer. The prospects and challenges of nano-ICG diagnostic and therapeutic methods in clinical applications are also discussed.
Graphical Abstract
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Karmarkar R, Benjafield A, Aroori S. The Role of Colour Segmented Fluorescence (CSF) Mode and Same-day Administration of Low-dose Indocyanine Green in Liver Surgery: Our Initial Experience : Indocyanine Green Fluorescence Guided Resection of Liver Tumours. J Fluoresc 2024; 34:2133-2138. [PMID: 37713013 DOI: 10.1007/s10895-023-03434-6] [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: 07/27/2023] [Accepted: 09/05/2023] [Indexed: 09/16/2023]
Abstract
Indocyanine green (ICG) fluorescence image guidance (I-FIGS) is increasingly used in liver surgery. Several regimens have been described regarding the optimum timing and dose of administration. This study presents our early experience with utilising monochromatic Colour Segmented Fluorescence (CSF)-mode and same-day administration of low-dose-ICG in the resection of liver tumours. Between November 2020 and March 2022, I-FIGS was used in 15 patients with suspected liver tumours. ICG was administered intravenously at 0.02 to 0.05 mg/kg dose 2-3 h before surgery. ICG camera was switched to CSF-grey-scale mode to visualise the tumour and to avoid the interference of the green background liver. Using the SPY-CSF mode, the image was scaled to near-infra-red (NIR) fluorescence intensity to accurately identify the tumours and resection margins. Fifteen patients (eight males) with a median age of 71 years (range: 36-86) underwent I-FIGS. Of these, 67% underwent laparoscopic liver surgery, 78% had non-anatomical resections, and 33% underwent redo liver surgery. The mean tumour size was 40.6 mm (SD+/-41 mm). The median number of tumours was two (1-7). All colorectal liver metastases (CRLM) had a signet ring appearance. Hepatocellular carcinomas (HCC) showed partial fluorescence. Tumours were well/moderately differentiated, with CRLM in 86% and HCC in two patients. The R0 resection rate was 72%. In our experience, low-dose-ICG administered at least 2-3 h before surgery can identify liver tumours and their margins in CSF-grey-scale mode. Further research is needed to evaluate its role in reducing R1 resection rates and surgical outcomes.
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Affiliation(s)
- Rahi Karmarkar
- Peninsula HPB Unit, University Hospitals Plymouth NHS Trust & University of Plymouth, Plymouth, UK
- Doctoral College, Faculty of Health, University of Plymouth, Plymouth, UK
| | - Anastasia Benjafield
- Peninsula HPB Unit, University Hospitals Plymouth NHS Trust & University of Plymouth, Plymouth, UK
| | - Somaiah Aroori
- Peninsula HPB Unit, University Hospitals Plymouth NHS Trust & University of Plymouth, Plymouth, UK.
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Kumagai K, Yoshida M, Ishida H, Ishizuka N, Ohashi M, Makuuchi R, Hayami M, Ida S, Yoshimizu S, Horiuchi Y, Ishiyama A, Yoshio T, Hirasawa T, Fujisaki J, Nunobe S. Diagnostic Performance of Near-Infrared Fluorescent Marking Clips in Laparoscopic Gastrectomy. J Surg Res 2024; 300:157-164. [PMID: 38815514 DOI: 10.1016/j.jss.2024.05.003] [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: 09/12/2023] [Revised: 04/24/2024] [Accepted: 05/06/2024] [Indexed: 06/01/2024]
Abstract
INTRODUCTION Accurate tumor localization and resection margin acquisition are essential in gastric cancer surgery. Preoperative placement of marking clips in laparoscopic gastrectomy as well as intraoperative gastroscopy can be used for gastric cancer surgery. However, these procedures are not available at all institutions. We conducted a prospective clinical trial to investigate the diagnostic performance of near-infrared fluorescent clips (ZEOCLIP FS) in laparoscopic gastrectomy. MATERIALS AND METHODS Patients with gastric cancer or neuroendocrine tumor in whom laparoscopic distal, pylorus-preserving, or proximal gastrectomy was planned were enrolled (n = 20) in this study. Fluorescent clips were placed proximal and/or distal to the tumor via gastroscopy on the day before surgery. During surgery, the clips were detected using a fluorescent laparoscope, and suturing was performed where fluorescence was detected. The clip locations were then confirmed via gastroscopy, and the stomach was transected. The primary endpoint was the detection rate of the marking clips using fluorescence, and the secondary endpoints were complications and distance between the clips and stitches. RESULTS Among the 20 patients enrolled, distal and pylorus-preserving gastrectomies were performed in 18 and 2 patients, respectively. All clips were detected in 15 patients, indicating a detection rate of 75.0% (90% confidence interval: 54.4%-89.6%). Furthermore, no complications related to the clips were observed. The median distance between the clips and stitches was 5 (range, 0-10) mm. CONCLUSIONS We report the feasibility and safety of preoperative placement and intraoperative detection of near-infrared fluorescent marking clips in laparoscopic gastrectomy.
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Affiliation(s)
- Koshi Kumagai
- Department of Gastroenterological Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Masashi Yoshida
- Department of Surgery, International University of Health and Welfare Hospital, Tochigi, Japan
| | - Hiroki Ishida
- Department of Gastroenterological Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Naoki Ishizuka
- Clinical Trial Planning and Management, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Manabu Ohashi
- Department of Gastroenterological Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Rie Makuuchi
- Department of Gastroenterological Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Masaru Hayami
- Department of Gastroenterological Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Satoshi Ida
- Department of Gastroenterological Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Shoichi Yoshimizu
- Department of Gastroenterology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Yusuke Horiuchi
- Department of Gastroenterology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Akiyoshi Ishiyama
- Department of Gastroenterology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Toshiyuki Yoshio
- Department of Gastroenterology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Toshiaki Hirasawa
- Department of Gastroenterology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Junko Fujisaki
- Department of Gastroenterology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Souya Nunobe
- Department of Gastroenterological Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan.
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Brookes MJ, Chan CD, Crowley TP, Ragbir M, Ghosh KM, Beckingsale T, Rankin KS. Intraoperative near-infrared fluorescence guided surgery using indocyanine green (ICG) may aid the surgical removal of benign bone and soft tissue tumours. Surg Oncol 2024; 55:102091. [PMID: 38833894 DOI: 10.1016/j.suronc.2024.102091] [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: 01/18/2024] [Revised: 04/08/2024] [Accepted: 05/27/2024] [Indexed: 06/06/2024]
Abstract
BACKGROUND Benign bone and soft tissue tumours encompass a broad, heterogenous range of tumours with varying clinical characteristics. These are often managed surgically with either curettage or marginal excision, but unfortunately have high rates of local recurrence. Indocyanine green (ICG) is a fluorescent dye which can be used to identify solid malignancies intraoperatively but its use is not yet established in benign bone and soft tissue tumours. This study aims to assess whether these tumours fluoresce when administered with ICG pre-operatively and whether this helps surgeons to identify tumour intra-operatively. PATIENTS AND METHODS Patients with locally aggressive benign bone and soft tissue tumours were administered with 25-75 mg of ICG preoperatively at the induction of anaesthesia. Fluorescence was imaged intraoperatively using the Stryker SPY-PHI camera. RESULTS Of the 12 patients included, 11 tumours fluoresced. The surgeons felt the fluorescence guided the procedure in 7 out of the 11 cases which fluoresced. It was felt to be particularly useful in the curettage of bone tumours, in which curettage could be repeated until the absence of fluorescence on imaging. After 12 months, no patients had local recurrence of the tumour. There were no adverse events recorded in this study and surgeons found the technology acceptable. CONCLUSIONS The use of ICG for fluorescence guided surgery is a promising technology to improve outcomes of surgery for benign bone and soft tissue tumours. Further, longer term, study with a control arm is needed to identify whether it results in a reduction in the local recurrence rate.
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Affiliation(s)
- Marcus J Brookes
- North of England Bone and Soft Tissue Tumour Service, Royal Victoria Infirmary, Queen Victoria Road, Newcastle Upon Tyne NE1 4LP, UK; Translational and Clinical Research Institute, Newcastle University, Newcastle Upon Tyne NE1 7RU, UK.
| | - Corey D Chan
- North of England Bone and Soft Tissue Tumour Service, Royal Victoria Infirmary, Queen Victoria Road, Newcastle Upon Tyne NE1 4LP, UK; Translational and Clinical Research Institute, Newcastle University, Newcastle Upon Tyne NE1 7RU, UK
| | - Timothy P Crowley
- North of England Bone and Soft Tissue Tumour Service, Royal Victoria Infirmary, Queen Victoria Road, Newcastle Upon Tyne NE1 4LP, UK
| | - Maniram Ragbir
- North of England Bone and Soft Tissue Tumour Service, Royal Victoria Infirmary, Queen Victoria Road, Newcastle Upon Tyne NE1 4LP, UK
| | - Kanishka M Ghosh
- North of England Bone and Soft Tissue Tumour Service, Royal Victoria Infirmary, Queen Victoria Road, Newcastle Upon Tyne NE1 4LP, UK
| | - Thomas Beckingsale
- North of England Bone and Soft Tissue Tumour Service, Royal Victoria Infirmary, Queen Victoria Road, Newcastle Upon Tyne NE1 4LP, UK
| | - Kenneth S Rankin
- North of England Bone and Soft Tissue Tumour Service, Royal Victoria Infirmary, Queen Victoria Road, Newcastle Upon Tyne NE1 4LP, UK; Translational and Clinical Research Institute, Newcastle University, Newcastle Upon Tyne NE1 7RU, UK
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10
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Morales-Conde S, Navarro-Morales L, Moreno-Suero F, Balla A, Licardie E. Fluorescence and tracers in surgery: the coming future. Cir Esp 2024; 102 Suppl 1:S45-S60. [PMID: 38851317 DOI: 10.1016/j.cireng.2024.05.011] [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: 05/07/2024] [Accepted: 05/23/2024] [Indexed: 06/10/2024]
Abstract
The revolution that we are seeing in the world of surgery will determine the way we understand surgical approaches in coming years. Since the implementation of minimally invasive surgery, innovations have constantly been developed to allow the laparoscopic approach to go further and be applied to more and more procedures. In recent years, we have been in the middle of another revolutionary era, with robotic surgery, the application of artificial intelligence and image-guided surgery. The latter includes 3D reconstructions for surgical planning, virtual reality, holograms or tracer-guided surgery, where ICG-guided fluorescence has provided a different perspective on surgery. ICG has been used to identify anatomical structures, assess tissue perfusion, and identify tumors or tumor lymphatic drainage. But the most important thing is that this technology has come hand in hand with the potential to develop other types of tracers that will facilitate the identification of tumor cells and ureters, as well as different light beams to identify anatomical structures. These will lead to other types of systems to assess tissue perfusion without the use of tracers, such as hyperspectral imaging. Combined with the upcoming introduction of ICG quantification, these developments represent a real revolution in the surgical world. With the imminent implementation of these technological advances, a review of their clinical application in general surgery is timely, and this review serves that aim.
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Affiliation(s)
- Salvador Morales-Conde
- Servicio de Cirugía General y Digestiva, Hospital Universitario Virgen Macarena, Facultad de Medicina, Universidad de Sevilla, Sevilla, Spain; Servicio de Cirugía General y Digestiva, Hospital Quironsalud Sagrado Corazón, Sevilla, Spain.
| | - Laura Navarro-Morales
- Servicio de Cirugía General y Digestiva, Hospital Quironsalud Sagrado Corazón, Sevilla, Spain.
| | - Francisco Moreno-Suero
- Servicio de Cirugía General y Digestiva, Hospital Quironsalud Sagrado Corazón, Sevilla, Spain.
| | - Andrea Balla
- Servicio de Cirugía General y Digestiva, Hospital Universitario Virgen Macarena, Facultad de Medicina, Universidad de Sevilla, Sevilla, Spain; Servicio de Cirugía General y Digestiva, Hospital Quironsalud Sagrado Corazón, Sevilla, Spain.
| | - Eugenio Licardie
- Servicio de Cirugía General y Digestiva, Hospital Universitario Virgen Macarena, Facultad de Medicina, Universidad de Sevilla, Sevilla, Spain; Servicio de Cirugía General y Digestiva, Hospital Quironsalud Sagrado Corazón, Sevilla, Spain.
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11
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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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Zhang QJ, Cao ZC, Zhu Q, Sun Y, Li RD, Tong JL, Zheng Q. Application value of indocyanine green fluorescence imaging in guiding sentinel lymph node biopsy diagnosis of gastric cancer: Meta-analysis. World J Gastrointest Surg 2024; 16:1883-1893. [PMID: 38983339 PMCID: PMC11230008 DOI: 10.4240/wjgs.v16.i6.1883] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/05/2024] [Revised: 05/12/2024] [Accepted: 05/24/2024] [Indexed: 06/27/2024] Open
Abstract
BACKGROUND Gastric cancer is a common malignant tumor of the digestive system worldwide, and its early diagnosis is crucial to improve the survival rate of patients. Indocyanine green fluorescence imaging (ICG-FI), as a new imaging technology, has shown potential application prospects in oncology surgery. The meta-analysis to study the application value of ICG-FI in the diagnosis of gastric cancer sentinel lymph node biopsy is helpful to comprehensively evaluate the clinical effect of this technology and provide more reliable guidance for clinical practice. AIM To assess the diagnostic efficacy of optical imaging in conjunction with indocyanine green (ICG)-guided sentinel lymph node (SLN) biopsy for gastric cancer. METHODS Electronic databases such as PubMed, Embase, Medline, Web of Science, and the Cochrane Library were searched for prospective diagnostic tests of optical imaging combined with ICG-guided SLN biopsy. Stata 12.0 software was used for analysis by combining the "bivariable mixed effect model" with the "midas" command. The true positive value, false positive value, false negative value, true negative value, and other information from the included literature were extracted. A literature quality assessment map was drawn to describe the overall quality of the included literature. A forest plot was used for heterogeneity analysis, and P < 0.01 was considered to indicate statistical significance. A funnel plot was used to assess publication bias, and P < 0.1 was considered to indicate statistical significance. The summary receiver operating characteristic (SROC) curve was used to calculate the area under the curve (AUC) to determine the diagnostic accuracy. If there was interstudy heterogeneity (I 2 > 50%), meta-regression analysis and subgroup analysis were performed. RESULTS Optical imaging involves two methods: Near-infrared (NIR) imaging and fluorescence imaging. A combination of optical imaging and ICG-guided SLN biopsy was useful for diagnosis. The positive likelihood ratio was 30.39 (95%CI: 0.92-1.00), the sensitivity was 0.95 (95%CI: 0.82-0.99), and the specificity was 1.00 (95%CI: 0.92-1.00). The negative likelihood ratio was 0.05 (95%CI: 0.01-0.20), the diagnostic odds ratio was 225.54 (95%CI: 88.81-572.77), and the SROC AUC was 1.00 (95%CI: The crucial values were sensitivity = 0.95 (95%CI: 0.82-0.99) and specificity = 1.00 (95%CI: 0.92-1.00). The Deeks method revealed that the "diagnostic odds ratio" funnel plot of SLN biopsy for gastric cancer was significantly asymmetrical (P = 0.01), suggesting significant publication bias. Further meta-subgroup analysis revealed that, compared with fluorescence imaging, NIR imaging had greater sensitivity (0.98 vs 0.73). Compared with optical imaging immediately after ICG injection, optical imaging after 20 minutes obtained greater sensitivity (0.98 vs 0.70). Compared with that of patients with an average SLN detection number < 4, the sensitivity of patients with a SLN detection number ≥ 4 was greater (0.96 vs 0.68). Compared with hematoxylin-eosin (HE) staining, immunohistochemical (+ HE) staining showed greater sensitivity (0.99 vs 0.84). Compared with subserous injection of ICG, submucosal injection achieved greater sensitivity (0.98 vs 0.40). Compared with 5 g/L ICG, 0.5 and 0.05 g/L ICG had greater sensitivity (0.98 vs 0.83), and cT1 stage had greater sensitivity (0.96 vs 0.72) than cT2 to cT3 clinical stage. Compared with that of patients ≤ 26, the sensitivity of patients > 26 was greater (0.96 vs 0.65). Compared with the literature published before 2010, the sensitivity of the literature published after 2010 was greater (0.97 vs 0.81), and the differences were statistically significant (all P < 0.05). CONCLUSION For the diagnosis of stomach cancer, optical imaging in conjunction with ICG-guided SLN biopsy is a therapeutically viable approach, especially for early gastric cancer. The concentration of ICG used in the SLN biopsy of gastric cancer may be too high. Moreover, NIR imaging is better than fluorescence imaging and may obtain higher sensitivity.
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Affiliation(s)
- Qi-Jia Zhang
- Department of Oncology, The Second Hospital of Nanjing, Affiliated to Nanjing University of Chinese Medicine, Nanjing 210003, Jiangsu Province, China
| | - Zhi-Cheng Cao
- Department of Oncology, The Second Hospital of Nanjing, Affiliated to Nanjing University of Chinese Medicine, Nanjing 210003, Jiangsu Province, China
| | - Qin Zhu
- Department of Oncology, The Second Hospital of Nanjing, Affiliated to Nanjing University of Chinese Medicine, Nanjing 210003, Jiangsu Province, China
| | - Yu Sun
- Department of Oncology, The Second Hospital of Nanjing, Affiliated to Nanjing University of Chinese Medicine, Nanjing 210003, Jiangsu Province, China
| | - Rong-Da Li
- Department of Gastrointestinal Surgery, Qilu Hospital of Shandong University, Jinan 250063, Shandong Province, China
| | - Jin-Long Tong
- Department of Oncology, The Second Hospital of Nanjing, Affiliated to Nanjing University of Chinese Medicine, Nanjing 210003, Jiangsu Province, China
| | - Qin Zheng
- Department of Oncology, The Second Hospital of Nanjing, Affiliated to Nanjing University of Chinese Medicine, Nanjing 210003, Jiangsu Province, China
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Chen X, Li J, Roy S, Ullah Z, Gu J, Huang H, Yu C, Wang X, Wang H, Zhang Y, Guo B. Development of Polymethine Dyes for NIR-II Fluorescence Imaging and Therapy. Adv Healthc Mater 2024; 13:e2304506. [PMID: 38441392 DOI: 10.1002/adhm.202304506] [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: 12/18/2023] [Revised: 02/29/2024] [Indexed: 03/16/2024]
Abstract
Fluorescence imaging in the second near-infrared window (NIR-II) is burgeoning because of its higher imaging fidelity in monitoring physiological and pathological processes than clinical visible/the second near-infrared window fluorescence imaging. Notably, the imaging fidelity is heavily dependent on fluorescence agents. So far, indocyanine green, one of the polymethine dyes, with good biocompatibility and renal clearance is the only dye approved by the Food and Drug Administration, but it shows relatively low NIR-II brightness. Importantly, tremendous efforts are devoted to synthesizing polymethine dyes for imaging preclinically and clinically. They have shown feasibility in the customization of structure and properties to fulfill various needs in imaging and therapy. Herein, a timely update on NIR-II polymethine dyes, with a special focus on molecular design strategies for fluorescent, photoacoustic, and multimodal imaging, is offered. Furthermore, the progress of polymethine dyes in sensing pathological biomarkers and even reporting drug release is illustrated. Moreover, the NIR-II fluorescence imaging-guided therapies with polymethine dyes are summarized regarding chemo-, photothermal, photodynamic, and multimodal approaches. In addition, artificial intelligence is pointed out for its potential to expedite dye development. This comprehensive review will inspire interest among a wide audience and offer a handbook for people with an interest in NIR-II polymethine dyes.
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Affiliation(s)
- Xin Chen
- School of Science, Shenzhen Key Laboratory of Flexible Printed Electronics Technology, Shenzhen Key Laboratory of Advanced Functional Carbon Materials Research and Comprehensive Application, Harbin Institute of Technology, Shenzhen, 518055, China
| | - Jieyan Li
- School of Science, Shenzhen Key Laboratory of Flexible Printed Electronics Technology, Shenzhen Key Laboratory of Advanced Functional Carbon Materials Research and Comprehensive Application, Harbin Institute of Technology, Shenzhen, 518055, China
| | - Shubham Roy
- School of Science, Shenzhen Key Laboratory of Flexible Printed Electronics Technology, Shenzhen Key Laboratory of Advanced Functional Carbon Materials Research and Comprehensive Application, Harbin Institute of Technology, Shenzhen, 518055, China
| | - Zia Ullah
- School of Science, Shenzhen Key Laboratory of Flexible Printed Electronics Technology, Shenzhen Key Laboratory of Advanced Functional Carbon Materials Research and Comprehensive Application, Harbin Institute of Technology, Shenzhen, 518055, China
| | - Jingsi Gu
- Education Center and Experiments and Innovations, Harbin Institute of Technology, Shenzhen, 518055, China
| | - Haiyan Huang
- School of Science, Shenzhen Key Laboratory of Flexible Printed Electronics Technology, Shenzhen Key Laboratory of Advanced Functional Carbon Materials Research and Comprehensive Application, Harbin Institute of Technology, Shenzhen, 518055, China
| | - Chen Yu
- School of Science, Shenzhen Key Laboratory of Flexible Printed Electronics Technology, Shenzhen Key Laboratory of Advanced Functional Carbon Materials Research and Comprehensive Application, Harbin Institute of Technology, Shenzhen, 518055, China
- College of Chemistry and Environmental Engineering, Shenzhen University, Shenzhen, 518060, China
| | - Xuejin Wang
- School of Science, Shenzhen Key Laboratory of Flexible Printed Electronics Technology, Shenzhen Key Laboratory of Advanced Functional Carbon Materials Research and Comprehensive Application, Harbin Institute of Technology, Shenzhen, 518055, China
| | - Han Wang
- School of Science, Shenzhen Key Laboratory of Flexible Printed Electronics Technology, Shenzhen Key Laboratory of Advanced Functional Carbon Materials Research and Comprehensive Application, Harbin Institute of Technology, Shenzhen, 518055, China
| | - Yinghe Zhang
- School of Science, Shenzhen Key Laboratory of Flexible Printed Electronics Technology, Shenzhen Key Laboratory of Advanced Functional Carbon Materials Research and Comprehensive Application, Harbin Institute of Technology, Shenzhen, 518055, China
| | - Bing Guo
- School of Science, Shenzhen Key Laboratory of Flexible Printed Electronics Technology, Shenzhen Key Laboratory of Advanced Functional Carbon Materials Research and Comprehensive Application, Harbin Institute of Technology, Shenzhen, 518055, China
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Kamimura T. Blood Flow in the Meniscus Can Be Visualized Arthroscopically Using an Intravenous Indocyanine Green Solution Diluted 10× in a Pig Model. Arthrosc Sports Med Rehabil 2024; 6:100932. [PMID: 39006800 PMCID: PMC11240037 DOI: 10.1016/j.asmr.2024.100932] [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: 11/23/2023] [Accepted: 03/17/2024] [Indexed: 07/16/2024] Open
Abstract
Purpose To determine the optimal indocyanine green (ICG) dose required for assessing vascularity in the meniscus using ICG fluorescence-guided knee arthroscopy in a pig model. Methods A 3-month-old Japanese esculent female pig was used in this study. Intravenous injections of ICG (25 mg) were administered with 2.0 mL of 5×, 10×, 100×, and 1,000× diluted solutions. An additional experiment was conducted to assess the microvasculature within the meniscus considering the results of the optimal dilution setting. A radial tear was purposely induced in the middle-to-posterior section of the medial meniscus to observe vascularity in the cross-sectioned meniscus; the optimal ICG dilution was administered. Results No fluorescence was detected in the meniscus with solutions diluted by 1,000× and 100×. Fluorescence was visualized at the anterior portion of the synovium and the anterior cruciate ligament using ICG diluted by 10×. Diluting ICG by 5×, contrast enhancement was too intense for observation. Therefore, the 10× diluted solution was considered the optimal setting for knee arthroscopy and observation of the radial tear. No fluorescence was observed in the cross section of the medial meniscus. Arterial hemorrhage was observed by stimulating the fluorescence-dyed synovium adjacent to the tear site. Through the additional waiting time after stimulating the tear site, the hemorrhage inside the meniscus became more intense. Conclusions The optimal dilution and dose setting of ICG for knee arthroscopy was 10× in a 2.0-mL intravenous injection. The meniscus showed no active blood flow, even in the red-red zone. This finding might support the notion that blood flow cannot be initiated, without synovial stimulation, even in vascular areas. Clinical Relevance This study could determine an ICG solution suitable for ICG fluorescence-guided knee arthroscopy. This finding could be valuable in future research focusing on case-specific meniscal vascularization under arthroscopy, particularly applying these findings to human meniscal treatment.
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Affiliation(s)
- Tamiko Kamimura
- Department of Orthopaedic Surgery, Tokorozawa Chuo Hospital, Tokorozawa, Japan
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15
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Varanese M, Arcieri S, Lauro A, Panetta C, Eberspacher C, Palma R, Mascagni D, Pontone S. Indocyanine Green Tattooing During Colonoscopy as a Guide to Laparoscopic Colorectal Cancer Surgery: A Literature Review. Surg Innov 2024; 31:103-110. [PMID: 37923725 DOI: 10.1177/15533506231209127] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2023]
Abstract
BACKGROUND Endoscopic tattooing of colorectal lesions has been performed employing several markers. The indocyanine green (ICG) that uses near infrared fluorescence technology, has been recently adopted in laparoscopic colorectal cancer surgery. This study aims to systematically review the international literature to validate the ICG in laparoscopic colorectal surgery, in order to include the ICG in the therapeutic protocol. METHODS Following AMSTAR 2 criteria, we performed a systematic review to evaluate the use of green indocyanine as a marker for preoperative endoscopic tattooing and for lymph nodes mapping. The study selection was conducted using the PubMed database from January 1989 to July 2022. RESULTS We identified 25 eligible studies. 13 based on fluorescent tumor localization in laparoscopic colorectal surgery using ICG while 12 of them reported the lymphatic road mapping and sentinel node identification by ICG using a near-infrared camera system. One study analyzed both topics. CONCLUSIONS In laparoscopic colorectal cancer surgery indocyanine green can be used to localize fluorescent tumors and mapping fluorescence lymph node. The use of ICG appears to be a valid and safe technique that helps the surgeon to achieve a better oncological radicality. However, the protocols need to be clarified by further studies.
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Affiliation(s)
- Marzia Varanese
- Department of Surgery, Sapienza University of Rome, Rome, Italy
| | - Stefano Arcieri
- Department of Surgery, Sapienza University of Rome, Rome, Italy
| | - Augusto Lauro
- Department of Surgery, Sapienza University of Rome, Rome, Italy
| | | | | | - Rossella Palma
- Department of Surgery, Sapienza University of Rome, Rome, Italy
| | | | - Stefano Pontone
- Department of Surgery, Sapienza University of Rome, Rome, Italy
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16
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Nguyen CL, Dayaratna N, Graham S, Azimi F, Mak C, Pulitano C, Warrier S. Evolution of Indocyanine Green Fluorescence in Breast and Axilla Surgery: An Australasian Experience. Life (Basel) 2024; 14:135. [PMID: 38255750 PMCID: PMC10821188 DOI: 10.3390/life14010135] [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: 11/20/2023] [Revised: 01/05/2024] [Accepted: 01/16/2024] [Indexed: 01/24/2024] Open
Abstract
The evolution of indocyanine green (ICG) fluorescence in breast and axilla surgery from an Australasian perspective is discussed in this narrative review with a focus on breast cancer and reconstruction surgery. The authors have nearly a decade of experience with ICG in a high-volume institution, which has resulted in publications and ongoing future research evaluating its use for predicting mastectomy skin flap perfusion for reconstruction, lymphatic mapping for sentinel lymph node (SLN) biopsy, and axillary reverse mapping (ARM) for prevention of lymphoedema. In the authors' experience, routine use of ICG angiography during breast reconstruction postmastectomy was demonstrated to be cost-effective for the reduction of ischemic complications in the Australian setting. A novel tracer combination, ICG-technetium-99m offered a safe and effective substitute to the "gold standard" dual tracer for SLN biopsy, although greater costs were associated with ICG. An ongoing trial will evaluate ARM node identification using ICG fluorescence during axillary lymph node dissection and potential predictive factors of ARM node involvement. These data add to the growing literature on ICG and allow future research to build on this to improve understanding of the potential benefits of fluorescence-guided surgery in breast cancer and reconstruction surgery.
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Affiliation(s)
- Chu Luan Nguyen
- Department of Breast Surgery, Chris O’Brien Lifehouse, Camperdown, NSW 2050, Australia; (S.G.); (F.A.); (C.M.); (S.W.)
- Department of Surgery, Royal Prince Alfred Hospital, Camperdown, NSW 2050, Australia;
- Department of Surgery, The University of Sydney, Camperdown, NSW 2050, Australia;
| | - Nirmal Dayaratna
- Department of Surgery, The University of Sydney, Camperdown, NSW 2050, Australia;
| | - Susannah Graham
- Department of Breast Surgery, Chris O’Brien Lifehouse, Camperdown, NSW 2050, Australia; (S.G.); (F.A.); (C.M.); (S.W.)
- Department of Surgery, Royal Prince Alfred Hospital, Camperdown, NSW 2050, Australia;
- Department of Surgery, The University of Sydney, Camperdown, NSW 2050, Australia;
| | - Farhad Azimi
- Department of Breast Surgery, Chris O’Brien Lifehouse, Camperdown, NSW 2050, Australia; (S.G.); (F.A.); (C.M.); (S.W.)
- Department of Surgery, The University of Sydney, Camperdown, NSW 2050, Australia;
| | - Cindy Mak
- Department of Breast Surgery, Chris O’Brien Lifehouse, Camperdown, NSW 2050, Australia; (S.G.); (F.A.); (C.M.); (S.W.)
| | - Carlo Pulitano
- Department of Surgery, Royal Prince Alfred Hospital, Camperdown, NSW 2050, Australia;
- Department of Surgery, The University of Sydney, Camperdown, NSW 2050, Australia;
| | - Sanjay Warrier
- Department of Breast Surgery, Chris O’Brien Lifehouse, Camperdown, NSW 2050, Australia; (S.G.); (F.A.); (C.M.); (S.W.)
- Department of Surgery, The University of Sydney, Camperdown, NSW 2050, Australia;
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Sikkenk DJ, Sterkenburg AJ, Burghgraef TA, Akol H, Schwartz MP, Arensman R, Verheijen PM, Nagengast WB, Consten ECJ. Robot-assisted fluorescent sentinel lymph node identification in early-stage colon cancer. Surg Endosc 2023; 37:8394-8403. [PMID: 37721591 PMCID: PMC10615938 DOI: 10.1007/s00464-023-10394-2] [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: 06/05/2023] [Accepted: 08/13/2023] [Indexed: 09/19/2023]
Abstract
BACKGROUND Patients with cT1-2 colon cancer (CC) have a 10-20% risk of lymph node metastases. Sentinel lymph node identification (SLNi) could improve staging and reduce morbidity in future organ-preserving CC surgery. This pilot study aimed to assess safety and feasibility of robot-assisted fluorescence-guided SLNi using submucosally injected indocyanine green (ICG) in patients with cT1-2N0M0 CC. METHODS Ten consecutive patients with cT1-2N0M0 CC were included in this prospective feasibility study. Intraoperative submucosal, peritumoral injection of ICG was performed during a colonoscopy. Subsequently, the near-infrared fluorescence 'Firefly' mode of the da Vinci Xi robotic surgical system was used for SLNi. SLNs were marked with a suture, after which a segmental colectomy was performed. The SLN was postoperatively ultrastaged using serial slicing and immunohistochemistry, in addition to the standard pathological examination of the specimen. Colonoscopy time, detection time (time from ICG injection to first SLNi), and total SLNi time were measured (time from the start of colonoscopy to start of segmental resection). Intraoperative, postoperative, and pathological outcomes were registered. RESULTS In all patients, at least one SLN was identified (mean 2.3 SLNs, SLN diameter range 1-13 mm). No tracer-related adverse events were noted. Median colonoscopy time was 12 min, detection time was 6 min, and total SLNi time was 30.5 min. Two patients had lymph node metastases present in the SLN, and there were no patients with false negative SLNs. No patient was upstaged due to ultrastaging of the SLN after an initial negative standard pathological examination. Half of the patients unexpectedly had pT3 tumours. CONCLUSIONS Robot-assisted fluorescence-guided SLNi using submucosally injected ICG in ten patients with cT1-2N0M0 CC was safe and feasible. SLNi was performed in an acceptable timespan and SLNs down to 1 mm were detected. All lymph node metastases would have been detected if SLN biopsy had been performed.
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Affiliation(s)
- Daan J Sikkenk
- Department of Surgery, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands
- Department of Surgery, Meander Medical Center, Maatweg 3, 3813 TZ, Amersfoort, The Netherlands
| | - Andrea J Sterkenburg
- Department of Gastroenterology and Hepatology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands
| | - Thijs A Burghgraef
- Department of Surgery, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands
- Department of Surgery, Meander Medical Center, Maatweg 3, 3813 TZ, Amersfoort, The Netherlands
| | - Halil Akol
- Department of Gastroenterology, Meander Medical Center, Maatweg 3, 3813 TZ, Amersfoort, The Netherlands
| | - Matthijs P Schwartz
- Department of Gastroenterology, Meander Medical Center, Maatweg 3, 3813 TZ, Amersfoort, The Netherlands
| | - René Arensman
- Department of Pathology, Meander Medical Center, Maatweg 3, 3813 TZ, Amersfoort, The Netherlands
| | - Paul M Verheijen
- Department of Surgery, Meander Medical Center, Maatweg 3, 3813 TZ, Amersfoort, The Netherlands
| | - Wouter B Nagengast
- Department of Gastroenterology and Hepatology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands
| | - Esther C J Consten
- Department of Surgery, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands.
- Department of Surgery, Meander Medical Center, Maatweg 3, 3813 TZ, Amersfoort, The Netherlands.
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Baldari L, Boni L, Cassinotti E. Lymph node mapping with ICG near-infrared fluorescence imaging: technique and results. MINIM INVASIV THER 2023; 32:213-221. [PMID: 37261486 DOI: 10.1080/13645706.2023.2217916] [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: 01/16/2023] [Accepted: 05/18/2023] [Indexed: 06/02/2023]
Abstract
PURPOSE Lymphadenectomy represents a fundamental step during gastrointestinal cancer resection, as the removal of an adequate number of lymph nodes is crucial to define the stage of the disease and prognosis. Lymphadenectomy during gastric and colorectal resection and adrenalectomy for cancer are technically demanding and can be associated with risk of bleeding. To date, lymphadenectomy is often performed without any visual aid. Indocyanine green fluorescence for lymph node mapping can provide better intraoperative visualization. The purpose of this review is to report the current evidence on this topic. MATERIALS AND METHODS A systematic research of the electronic databases Medline, Embase and Google Scholar was conducted from the inception to December 2022. RESULTS This review summarizes the current evidence of techniques and results of fluorescence guided lymphatic mapping during gastrointestinal and adrenal surgery. CONCLUSION According to this review, ICG guided lymphadenectomy for gastrointestinal tumours and adrenocortical carcinoma is feasible and safe. In gastrointestinal tumours it allows higher number of harvested lymph nodes.
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Affiliation(s)
- Ludovica Baldari
- Department of General and Minimally Invasive Surgery, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Luigi Boni
- Department of General and Minimally Invasive Surgery, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Elisa Cassinotti
- Department of General and Minimally Invasive Surgery, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
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Nguyen CL, Zhou M, Easwaralingam N, Seah JL, Azimi F, Mak C, Pulitano C, Warrier S. Novel Dual Tracer Indocyanine Green and Radioisotope Versus Gold Standard Sentinel Lymph Node Biopsy in Breast Cancer: The GREENORBLUE Trial. Ann Surg Oncol 2023; 30:6520-6527. [PMID: 37402976 PMCID: PMC10507001 DOI: 10.1245/s10434-023-13824-6] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2023] [Accepted: 06/14/2023] [Indexed: 07/06/2023]
Abstract
BACKGROUND The methods for sentinel lymph node (SLN) biopsy in breast cancer have been variable in type and number of tracers. Some units have abandoned the use of blue dye (BD) due to adverse reactions. Fluorescence-guided biopsy with indocyanine green (ICG) is a relatively novel technique. This study compared the clinical efficacy and costs between novel dual tracer ICG and radioisotope (ICG-RI) with "gold standard" BD and radioisotope (BD-RI). METHODS Single-surgeon study of 150 prospective patients with early breast cancer undergoing SLN biopsy (2021-2022) using ICG-RI compared with a retrospective cohort of 150 consecutive previous patients using BD-RI. Number of SLNs identified, rate of failed mapping, identification of metastatic SLNs, and adverse reactions were compared between techniques. Cost-minimisation analysis performed by using Medicare item numbers and micro-costing analysis. RESULTS Total number of SLNs identified with ICG-RI and BD-RI was 351 and 315, respectively. Mean number of SLNs identified with ICG-RI and BD-RI was 2.3 (standard deviation [SD] 1.4) and 2.1 (SD 1.1), respectively (p = 0.156). There were no cases of failed mapping with either dual technique. Metastatic SLNs were identified in 38 (25.3%) ICG-RI patients compared with 30 (20%) BD-RI patients (p = 0.641). There were no adverse reactions to ICG, whereas four cases of skin tattooing and anaphylaxis were associated with BD (p = 0.131). ICG-RI cost an additional AU$197.38 per case in addition to the initial cost for the imaging system. CLINICAL TRIAL REGISTRATION ACTRN12621001033831. CONCLUSIONS Novel tracer combination, ICG-RI, provided an effective and safe alternative to "gold standard" dual tracer. The caveat was the significantly greater costs associated with ICG.
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Affiliation(s)
- Chu Luan Nguyen
- Department of Breast Surgery, Chris O'Brien Lifehouse, Camperdown, NSW, Australia.
- Department of Surgery, Royal Prince Alfred Hospital, Camperdown, NSW, Australia.
- Department of Surgery, The University of Sydney, Camperdown, NSW, Australia.
| | - Michael Zhou
- Department of Surgery, The University of Sydney, Camperdown, NSW, Australia
| | - Neshanth Easwaralingam
- Department of Breast Surgery, Chris O'Brien Lifehouse, Camperdown, NSW, Australia
- Department of Surgery, The University of Sydney, Camperdown, NSW, Australia
| | - Jue Li Seah
- Department of Breast Surgery, Chris O'Brien Lifehouse, Camperdown, NSW, Australia
- Department of Surgery, Royal Prince Alfred Hospital, Camperdown, NSW, Australia
- Department of Surgery, The University of Sydney, Camperdown, NSW, Australia
| | - Farhad Azimi
- Department of Breast Surgery, Chris O'Brien Lifehouse, Camperdown, NSW, Australia
- Department of Surgery, The University of Sydney, Camperdown, NSW, Australia
| | - Cindy Mak
- Department of Breast Surgery, Chris O'Brien Lifehouse, Camperdown, NSW, Australia
- Department of Surgery, The University of Sydney, Camperdown, NSW, Australia
| | - Carlo Pulitano
- Department of Surgery, Royal Prince Alfred Hospital, Camperdown, NSW, Australia
- Department of Surgery, The University of Sydney, Camperdown, NSW, Australia
| | - Sanjay Warrier
- Department of Breast Surgery, Chris O'Brien Lifehouse, Camperdown, NSW, Australia
- Department of Surgery, Royal Prince Alfred Hospital, Camperdown, NSW, Australia
- Department of Surgery, The University of Sydney, Camperdown, NSW, Australia
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20
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Watanabe J, Ohya H, Sakai J, Suwa Y, Goto K, Nakagawa K, Ozawa M, Ishibe A, Suwa H, Kunisaki C, Endo I. Long-term outcomes of indocyanine green fluorescence imaging-guided laparoscopic lateral pelvic lymph node dissection for clinical stage II/III middle-lower rectal cancer: a propensity score-matched cohort study. Tech Coloproctol 2023; 27:759-767. [PMID: 36773172 DOI: 10.1007/s10151-023-02761-x] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/28/2022] [Accepted: 01/25/2023] [Indexed: 02/12/2023]
Abstract
BACKGROUND We previously reported that indocyanine green fluorescence imaging (ICG-FI)-guided laparoscopic lateral pelvic lymph node dissection (LPLND) was able to increase the total number of harvested lateral pelvic lymph nodes without impairing functional preservation. However, the long-term outcomes of ICG-FI-guided laparoscopic LPLND have not been evaluated. The aim of the present study was to compare the long-term outcomes of ICG-FI-guided laparoscopic LPLND to conventional laparoscopic LPLND without ICG-FI. METHODS This was a retrospective, multi-institutional study with propensity score matching. The study population included consecutive patients with middle-low rectal cancer (clinical stage II to III) who underwent laparoscopic LPLND between January 2013 and February 2018. The main evaluation items in this study were the 3-year overall survival, relapse-free survival (RFS), local recurrence rate, and lateral local recurrence (LLR) rate. RESULTS A total of 172 patients with middle-lower rectal cancer who had undergone laparoscopic LPLND were included in this study. After propensity score matching, 58 patients were matched in each of the ICG-FI and non-ICG-FI groups. There were no substantial differences in the baseline characteristics between the two groups. The ICG-FI group and non-ICG-FI group included 40 and 38 women and had a median age of 65 (IQR 60-72) and 66 (IQR 60-73) years, respectively. The median follow-up for all patients was 63.7 (IQR 51.3-76.8) months. The estimated respective 3-year overall survival, RFS, and local recurrence rates were 93.1%, 70.7%, and 5.2% in the ICG-FI group and 85.9%, 71.7%, and 12.8% in the non-ICG-FI group (p = 0.201, 0.653, 0.391). The 3-year cumulative LLR rate was 0% in the ICG-FI group and 9.3% in the non-ICG-FI group (p = 0.048). CONCLUSIONS This study revealed that laparoscopic LPLND combined with ICG-FI was able to decrease the LLR rate. It appears that ICG-FI could contribute to improving the quality of laparoscopic LPLND and strengthening local control of the lateral pelvis. TRIALS REGISTRATION This study was registered with the Japanese Clinical Trials Registry as UMIN000041372 ( http://www.umin.ac.jp/ctr/index.htm ).
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Affiliation(s)
- J Watanabe
- Department of Surgery, Gastroenterological Center, Yokohama City University Medical Center, 4-57, Urafune-Cho, Minami-Ku, Yokohama, 232-0024, Japan.
- Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
| | - H Ohya
- Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Japan
| | - J Sakai
- Department of Surgery, Yokosuka Kyosai Hospital, Yokosuka, Japan
| | - Y Suwa
- Department of Surgery, Gastroenterological Center, Yokohama City University Medical Center, 4-57, Urafune-Cho, Minami-Ku, Yokohama, 232-0024, Japan
| | - K Goto
- Department of Surgery, Gastroenterological Center, Yokohama City University Medical Center, 4-57, Urafune-Cho, Minami-Ku, Yokohama, 232-0024, Japan
| | - K Nakagawa
- Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Japan
| | - M Ozawa
- Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Japan
| | - A Ishibe
- Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Japan
| | - H Suwa
- Department of Surgery, Yokosuka Kyosai Hospital, Yokosuka, Japan
| | - C Kunisaki
- Department of Surgery, Gastroenterological Center, Yokohama City University Medical Center, 4-57, Urafune-Cho, Minami-Ku, Yokohama, 232-0024, Japan
| | - I Endo
- Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Japan
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Lucas K, Melling N, Giannou AD, Reeh M, Mann O, Hackert T, Izbicki JR, Perez D, Grass JK. Lymphatic Mapping in Colon Cancer Depending on Injection Time and Tracing Agent: A Systematic Review and Meta-Analysis of Prospective Designed Studies. Cancers (Basel) 2023; 15:3196. [PMID: 37370806 PMCID: PMC10296374 DOI: 10.3390/cancers15123196] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2023] [Revised: 06/08/2023] [Accepted: 06/13/2023] [Indexed: 06/29/2023] Open
Abstract
An optimized lymph node yield leads to better survival in colon cancer, but extended lymphadenectomy is not associated with survival benefits. Lymphatic mapping shows several colon cancers feature aberrant drainage pathways inducing local recurrence when not resected. Currently, different protocols exist for lymphatic mapping procedures. This meta-analysis assessed which protocol has the best capacity to detect tumor-draining and possibly metastatic lymph nodes. A systematic review was conducted according to PRISMA guidelines, including prospective trials with in vivo tracer application. The risk of bias was evaluated using the QUADAS-2 tool. Traced lymph nodes, total resected lymph nodes, and aberrant drainage detection rate were analyzed. Fifty-eight studies met the inclusion criteria, of which 42 searched for aberrant drainage. While a preoperative tracer injection significantly increased the traced lymph node rates compared to intraoperative tracing (30.1% (15.4, 47.3) vs. 14.1% (11.9, 16.5), p = 0.03), no effect was shown for the tracer used (p = 0.740) or the application sites comparing submucosal and subserosal injection (22.9% (14.1, 33.1) vs. 14.3% (12.1, 16.8), p = 0.07). Preoperative tracer injection resulted in a significantly higher rate of detected aberrant lymph nodes compared to intraoperative injection (26.3% [95% CI 11.5, 44.0] vs. 2.5% [95% CI 0.8, 4.7], p < 0.001). Analyzing 112 individual patient datasets from eight studies revealed a significant impact on aberrant drainage detection for injection timing, favoring preoperative over intraoperative injection (OR 0.050 [95% CI 0.010-0.176], p < 0.001) while indocyanine green presented itself as the superior tracer (OR 0.127 [95% CI 0.018-0.528], p = 0.012). Optimized lymphatic mapping techniques result in significantly higher detection of aberrant lymphatic drainage patterns and thus enable a personalized approach to reducing local recurrence.
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Affiliation(s)
- Katharina Lucas
- Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Martinistraße 52, 20246 Hamburg, Germany; (K.L.); (N.M.); (A.D.G.); (M.R.); (O.M.); (T.H.); (J.R.I.); (D.P.)
- Department of Visceral, Thoracic, Vascular Surgery and Angiology, City Hospital Triemli, Birmensdorferstrasse 497, 8063 Zürich, Switzerland
| | - Nathaniel Melling
- Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Martinistraße 52, 20246 Hamburg, Germany; (K.L.); (N.M.); (A.D.G.); (M.R.); (O.M.); (T.H.); (J.R.I.); (D.P.)
| | - Anastasios D. Giannou
- Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Martinistraße 52, 20246 Hamburg, Germany; (K.L.); (N.M.); (A.D.G.); (M.R.); (O.M.); (T.H.); (J.R.I.); (D.P.)
| | - Matthias Reeh
- Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Martinistraße 52, 20246 Hamburg, Germany; (K.L.); (N.M.); (A.D.G.); (M.R.); (O.M.); (T.H.); (J.R.I.); (D.P.)
| | - Oliver Mann
- Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Martinistraße 52, 20246 Hamburg, Germany; (K.L.); (N.M.); (A.D.G.); (M.R.); (O.M.); (T.H.); (J.R.I.); (D.P.)
| | - Thilo Hackert
- Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Martinistraße 52, 20246 Hamburg, Germany; (K.L.); (N.M.); (A.D.G.); (M.R.); (O.M.); (T.H.); (J.R.I.); (D.P.)
| | - Jakob R. Izbicki
- Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Martinistraße 52, 20246 Hamburg, Germany; (K.L.); (N.M.); (A.D.G.); (M.R.); (O.M.); (T.H.); (J.R.I.); (D.P.)
| | - Daniel Perez
- Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Martinistraße 52, 20246 Hamburg, Germany; (K.L.); (N.M.); (A.D.G.); (M.R.); (O.M.); (T.H.); (J.R.I.); (D.P.)
- Department of General and Visceral Surgery, Asklepios Hospital Altona, Paul-Ehrlich-Straße 1, 22763 Hamburg, Germany
| | - Julia K. Grass
- Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Martinistraße 52, 20246 Hamburg, Germany; (K.L.); (N.M.); (A.D.G.); (M.R.); (O.M.); (T.H.); (J.R.I.); (D.P.)
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22
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Xia S, Wu W, Luo L, Ma L, Yu L, Li Y. Indocyanine green fluorescence angiography decreases the risk of anastomotic leakage after rectal cancer surgery: a systematic review and meta-analysis. Front Med (Lausanne) 2023; 10:1157389. [PMID: 37250631 PMCID: PMC10213353 DOI: 10.3389/fmed.2023.1157389] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2023] [Accepted: 04/21/2023] [Indexed: 05/31/2023] Open
Abstract
Background Anastomotic leakage is a serious complication after rectal cancer resection. Intraoperative use of indocyanine green fluorescence angiography (ICGFA) can help prevent anastomotic leakage, but its use is controversial. We conducted a systematic review and meta-analysis to determine the efficacy of ICGFA in reducing anastomotic leakage. Methods Relevant data and research published until September 30, 2022, was retrieved from the PubMed, Embase, and Cochrane Library databases, and the difference in the incidence of anastomotic leakage after rectal cancer resection between ICGFA and standard treatment was compared. Results This meta-analysis included 22 studies with a total of 4,738 patients. The results showed that ICGFA use during surgery decreased the incidence of anastomotic leakage after rectal cancer surgery [risk ratio (RR) = 0.46; 95% confidence interval (95% CI), 0.39-0.56; p < 0.001]. Simultaneously, in subgroup analyses for different regions, ICGFA was found to be used to reduce the incidence of anastomotic leakage after rectal cancer surgery in Asia (RR = 0.33; 95% CI, 0.23-0.48; p < 0.00001) and Europe (RR = 0.38; 95% CI, 0.27-0.53; p < 0.00001) but not in North America (RR = 0.72; 95% CI, 0.40-1.29; p = 0.27). Regarding different levels of anastomotic leakage, ICGFA reduced the incidence of postoperative type A anastomotic leakage (RR = 0.25; 95% CI, 0.14-0.44; p < 0.00001) but did not reduce the incidence of type B (RR = 0.70; 95% CI, 0.38-1.31; p = 0.27) and type C (RR = 0.97; 95% CI, 0.51-1.97; p = 0.93) anastomotic leakages. Conclusion ICGFA has been linked to a reduction in anastomotic leakage after rectal cancer resection. However, multicenter randomized controlled trials with larger sample sizes are required for further validation.
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Affiliation(s)
- Shijun Xia
- Shenzhen Hospital of Guangzhou University of Chinese Medicine, Shenzhen, China
| | - Wenjiang Wu
- Shenzhen Hospital of Guangzhou University of Chinese Medicine, Shenzhen, China
| | - Lidan Luo
- Shenzhen Hospital of Guangzhou University of Chinese Medicine, Shenzhen, China
| | - Lijuan Ma
- Shenzhen Traditional Chinese Medicine Anorectal Hospital, Shenzhen, China
| | - Linchong Yu
- Shenzhen Hospital of Guangzhou University of Chinese Medicine, Shenzhen, China
| | - Yue Li
- Shenzhen Hospital of Guangzhou University of Chinese Medicine, Shenzhen, China
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23
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Cousins A, Krishnan S, Krishnan G, Pham N, Milanova V, Nelson M, Shetty A, Ikoma N, Thierry B. Preclinical evaluation of sentinel node localization in the stomach via mannose-labelled magnetic nanoparticles and indocyanine green. Surg Endosc 2023:10.1007/s00464-023-10099-6. [PMID: 37165173 PMCID: PMC10338612 DOI: 10.1007/s00464-023-10099-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2022] [Accepted: 04/23/2023] [Indexed: 05/12/2023]
Abstract
BACKGROUND Gastrectomy with extended (D2) lymphadenectomy is considered standard of care for gastric cancer to provide the best possible outcomes and pathologic staging. However, D2 gastrectomy is a technically demanding operation and reported to be associated with increased complications and mortality. Application of sentinel lymph node (SLN) concept in gastric cancer has the potential to reduce patient morbidity; however, SLN techniques are not established for gastrectomy, in part due to lack of practical tracers. An effective and convenient tracer with enhanced SLN accumulation is critically needed. METHODS Mannose-labelled magnetic tracer 'FerroTrace' and fluorescent dye indocyanine green (ICG) were injected laparoscopically into the stomach submucosa of 8 healthy swine under general anaesthesia. Intraoperative fluorescence imaging was used to highlight draining lymphatic pathways containing ICG, while preoperative T2-weighted MRI and ex vivo magnetometer probe measurements were used to identify nodes containing FerroTrace. Lymphadenectomy was performed either robotically (n = 2) or via laparotomy (n = 6). RESULTS Mixing ICG and FerroTrace ensured concurrence of fluorescent and magnetic signals in SLNs. An initial trial with robotic dissection removed all magnetic LNs (n = 4). In the subsequent laparotomy study that targeted all ICG-LNs based on intraoperative fluorescence imaging, dissection removed an average of 4.7 ± 1.2 fluorescent, and 2.0 ± 1.3 magnetic LNs per animal. Both MRI and magnetometer detected 100% of SLNs (n = 7). FerroTrace demonstrated high specificity to SLNs, which contained 76 ± 30% of total lymphotropic iron, and 88 ± 20 % of the overall magnetometer signal. CONCLUSIONS Through utilisation of this dual tracer approach, SLNs were identified via preoperative MRI, visualised intraoperatively with fluorescence imaging, and confirmed with a magnetometer. This combination pairs the sensitivity of ICG with SLN-specific FerroTrace and can be used for reliable SLN detection in gastric cancer, with potential applications in neoadjuvant therapy.
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Affiliation(s)
- Aidan Cousins
- Future Industries Institute, University of South Australia, Mawson Lakes Campus, Adelaide, SA, 5095, Australia.
| | - Shridhar Krishnan
- Department of Oral and Maxillofacial Surgery, The University of Adelaide, Adelaide, SA, 5000, Australia
| | - Giri Krishnan
- Department of Otolaryngology, Head and Neck Surgery, The University of Adelaide, Adelaide, SA, 5000, Australia
| | - Nguyen Pham
- Key Centre for Polymers and Colloids, School of Chemistry and University of Sydney Nano Institute, The University of Sydney, Sydney, NSW, 2006, Australia
| | - Valentina Milanova
- Future Industries Institute, University of South Australia, Mawson Lakes Campus, Adelaide, SA, 5095, Australia
| | - Melanie Nelson
- Ferronova Pty Ltd, MM-Building, Minerals Lane, Mawson Lakes, SA, 5095, Australia
| | - Anil Shetty
- Ferronova Pty Ltd, MM-Building, Minerals Lane, Mawson Lakes, SA, 5095, Australia
| | - Naruhiko Ikoma
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Benjamin Thierry
- Future Industries Institute, University of South Australia, Mawson Lakes Campus, Adelaide, SA, 5095, Australia
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24
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Savoie-White FH, Mailloux O. Use of intraoperative indocyanine green fluorescence in determining testicular viability in testicular torsion patients in rural settings: A case report. Int J Surg Case Rep 2023; 106:108247. [PMID: 37087930 PMCID: PMC10149194 DOI: 10.1016/j.ijscr.2023.108247] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2023] [Revised: 04/16/2023] [Accepted: 04/19/2023] [Indexed: 04/25/2023] Open
Abstract
INTRODUCTION AND IMPORTANCE Testicular torsion (TT) is the result of spermatic cord twisting which can lead to significant ischemia, making it a time-sensitive surgical emergency. General surgeons in rural centers may lack the resources to adequately evaluate the viability of the affected testicle. Indocyanine green fluorescence (IGF) has been increasingly used to assess vascular perfusion in general surgery cases. In this case report, we show the use of IGF in a rural setting to assess testicular viability in TT. CASE PRESENTATION A 17-year-old male was transferred to our rural regional hospital emergency department for sudden and persistent right scrotal pain. The onset of symptoms was approximately 52 h at presentation. TT was diagnosed with a doppler ultrasound by a radiologist. Urgent detorsion surgery was performed. Intraoperative assessment of viability was unclear after the usual means and IGF helped confirm the absence of testicle vascularization and the need for orchiectomy. CLINICAL DISCUSSION General surgeons in rural communities are called to manage TT with limited resources and experience. IGF is widely used in general surgery and urology. Animal studies and two case reports show potential benefits of IGF in TT. In our patient, IGF was useful to confirm without a doubt that the right testicle was ischemic and non-viable. CONCLUSION In a rural setting with limited access to radiology and distant urology coverage, IGF is an excellent resource to determine intraoperative blood flow in TT with uncertain viability.
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Affiliation(s)
| | - Olivier Mailloux
- Department of Surgery, Université Laval, Baie-Comeau, Québec, Canada.
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25
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Okamoto N, Al-Difaie Z, Scheepers MHMC, Heuvelings DJI, Rodríguez-Luna MR, Marescaux J, Diana M, Stassen LPS, Bouvy ND, Al-Taher M. Simultaneous, Multi-Channel, Near-Infrared Fluorescence Visualization of Mesenteric Lymph Nodes Using Indocyanine Green and Methylene Blue: A Demonstration in a Porcine Model. Diagnostics (Basel) 2023; 13:diagnostics13081469. [PMID: 37189570 DOI: 10.3390/diagnostics13081469] [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: 02/17/2023] [Revised: 03/17/2023] [Accepted: 03/24/2023] [Indexed: 05/17/2023] Open
Abstract
Near-infrared fluorescence (NIRF) image-guided surgery is a useful tool that can help reduce perioperative complications and improve tissue recognition. Indocyanine green (ICG) dye is the most frequently used in clinical studies. ICG NIRF imaging has been used for lymph node identification. However, there are still many challenges in lymph node identification by ICG. There is increasing evidence that methylene blue (MB), another clinically applicable fluorescent dye, can also be useful in the intraoperative fluorescence-guided identification of structures and tissues. We hypothesized that MB NIRF imaging could be used for lymph node identification. The aim of this study was to evaluate the feasibility of intraoperative lymph node fluorescence detection using intravenously (IV) administered MB and compare it to ICG via a camera that has two dedicated near-infrared (NIR) channels. Three pigs were used in this study. ICG (0.2 mg/kg) was administered via a peripheral venous catheter followed by immediate administration of MB (0.25 mg/kg). NIRF images were acquired as video recordings at different time points (every 10 min) over an hour using the QUEST SPECTRUM® 3 system (Quest Medical Imaging, Middenmeer, The Netherlands), which has two dedicated NIR channels for simultaneous intraoperative fluorescence guidance. The 800 nm channel was used to capture ICG fluorescence and the 700 nm channel was used for MB. The target (lymph nodes and small bowel) and the background (vessels-free field of the mesentery) were highlighted as the regions of interest (ROIs), and corresponding fluorescence intensities (FI) from these ROIs were measured. The target-to-background ratio (TBR) was then computed as the mean FI of the target minus the mean FI of the background divided by the mean FI of the background. In all included animals, a clear identification of lymph nodes was achieved at all time points. The mean TBR of ICG in lymph nodes and small bowel was 4.57 ± 1.00 and 4.37 ± 1.70, respectively for the overall experimental time. Regarding MB, the mean TBR in lymph nodes and small bowel was 4.60 ± 0.92 and 3.27 ± 0.62, respectively. The Mann-Whitney U test of the lymph node TBR/small bowel TBR showed that the TBR ratio of MB was statistically significantly higher than ICG. The fluorescence optical imaging technology used allows for double-wavelength assessment. This feasibility study proves that lymph nodes can be discriminated using two different fluorophores (MB and ICG) with different wavelengths. The results suggest that MB has a promising potential to be used to detect lymphatic tissue during image-guided surgery. Further preclinical trials are needed before clinical translation.
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Affiliation(s)
- Nariaki Okamoto
- IRCAD, Research Institute against Digestive Cancer, 67091 Strasbourg, France
- ICube Laboratory, Photonics Instrumentation for Health, 67081 Strasbourg, France
| | - Zaid Al-Difaie
- GROW School for Oncology and Developmental Biology, Maastricht University, 6229 ER Maastricht, The Netherlands
- Department of Surgery, Maastricht University Medical Center, 6229 ER Maastricht, The Netherlands
| | - Max H M C Scheepers
- GROW School for Oncology and Developmental Biology, Maastricht University, 6229 ER Maastricht, The Netherlands
- Department of Surgery, Maastricht University Medical Center, 6229 ER Maastricht, The Netherlands
| | - Danique J I Heuvelings
- Department of Surgery, Maastricht University Medical Center, 6229 ER Maastricht, The Netherlands
- NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University, 6229 HX Maastricht, The Netherlands
| | - María Rita Rodríguez-Luna
- IRCAD, Research Institute against Digestive Cancer, 67091 Strasbourg, France
- ICube Laboratory, Photonics Instrumentation for Health, 67081 Strasbourg, France
| | - Jacques Marescaux
- IRCAD, Research Institute against Digestive Cancer, 67091 Strasbourg, France
| | - Michele Diana
- IRCAD, Research Institute against Digestive Cancer, 67091 Strasbourg, France
- ICube Laboratory, Photonics Instrumentation for Health, 67081 Strasbourg, France
| | - Laurents P S Stassen
- Department of Surgery, Maastricht University Medical Center, 6229 ER Maastricht, The Netherlands
- NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University, 6229 HX Maastricht, The Netherlands
| | - Nicole D Bouvy
- Department of Surgery, Maastricht University Medical Center, 6229 ER Maastricht, The Netherlands
| | - Mahdi Al-Taher
- IRCAD, Research Institute against Digestive Cancer, 67091 Strasbourg, France
- Department of Surgery, Maastricht University Medical Center, 6229 ER Maastricht, The Netherlands
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Calcara C, Cocciolillo S, Marten Canavesio Y, Adamo V, Carenzi S, Lucci DI, Premoli A. Endoscopic fluorescent lymphography for gastric cancer. World J Gastrointest Endosc 2023; 15:32-43. [PMID: 36925646 PMCID: PMC10011894 DOI: 10.4253/wjge.v15.i2.32] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/02/2022] [Revised: 12/18/2022] [Accepted: 02/07/2023] [Indexed: 02/13/2023] Open
Abstract
Lymphography by radioisotope or dye is a well-known technique for visualizing the lymphatic drainage pattern in a neoplastic lesion and it is in use in gastric cancer. Indocyanine green (ICG) more recently has been validated in fluorescent lymphography studies and is under evaluation as a novel tracer agent in gastric cancer. The amount and dilution of ICG injected as well as the site and the time of the injection are not standardized. In our unit, endoscopic submucosal injections of ICG are made as 0.5 mg in 0.5 mL at four peritumoral sites the day before surgery (for a total of 2.0 mg in 2.0 mL). Detection instruments for ICG fluorescence are evolving. Near-infrared systems integrated into laparoscopic or robotic instruments (near-infrared fluorescence imaging) have shown the most promising results. ICG fluorescence recognizes the node that receives lymphatic flow directly from a primary tumor. This is defined as the sentinel lymph node, and it has a high predictive negative value at the cT1 stage, able to reduce the extent of gastrectomy and lymph node dissection. ICG also enhances the number of lymph nodes detected during extended lymphadenectomy for advanced gastric cancer. Nevertheless, the practical effects of ICG use in a single patient are not yet clear. Standardization of the technique and further studies are needed before fluorescent lymphography can be used extensively worldwide. Until then, current guidelines recommend an extensive lymphadenectomy as the standard approach for gastric cancer with suspected metastasis.
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Affiliation(s)
| | - Sila Cocciolillo
- Digestive Endoscopy Unit, Padre Pio Hospital, Vasto 66054, Italy
| | | | - Vincenzo Adamo
- General Surgery Unit, S. Andrea Hospital, Vercelli 13100, Italy
| | - Silvia Carenzi
- Digestive Endoscopy Unit, S. Andrea Hospital, Vercelli 13100, Italy
| | | | - Alberto Premoli
- Digestive Endoscopy Unit, S. Andrea Hospital, Vercelli 13100, Italy
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Cassinotti E, Boni L, Baldari L. Application of indocyanine green (ICG)-guided surgery in clinical practice: lesson to learn from other organs-an overview on clinical applications and future perspectives. Updates Surg 2023; 75:357-365. [PMID: 36203048 DOI: 10.1007/s13304-022-01361-y] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2022] [Accepted: 08/13/2022] [Indexed: 02/01/2023]
Abstract
Indocyanine green (ICG) fluorescence-guided surgery is a modality of intra-operative navigation that might support the surgeon with enhanced visualization of anatomical structures in real time. Over the last years, it has emerged as one of the most promising and rapidly developing technical innovations in surgery. The most popular current clinical applications include fluorescence cholangiography, bowel anastomotic perfusion assessment, fluorescence-guided lymphography for sentinel lymph-node identification and guided lymphadenectomy and the possible use in oncological surgery for the identification and localization of tumors and the diagnosis and treatment of peritoneal carcinosis. This paper provides an overview of the multiple fields of applications of ICG fluorescence-guided surgery in visceral and oncological surgery, discussing indications summarizing most recent and significative available literature and giving technical notes of use.
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Affiliation(s)
- E Cassinotti
- Department of Surgery, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Lombardia, Italy.
| | - L Boni
- Department of Surgery, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Lombardia, Italy
| | - L Baldari
- Department of Surgery, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Lombardia, Italy
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28
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Garoufalia Z, Wexner SD. Indocyanine Green Fluorescence Guided Surgery in Colorectal Surgery. J Clin Med 2023; 12:jcm12020494. [PMID: 36675423 PMCID: PMC9865296 DOI: 10.3390/jcm12020494] [Citation(s) in RCA: 24] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2022] [Revised: 01/04/2023] [Accepted: 01/04/2023] [Indexed: 01/11/2023] Open
Abstract
BACKGROUND Indocyanine green (ICG) imaging has been increasingly used for intraoperative guidance in colorectal surgery over the past decade. The aim of this study was to review and organize, according to different type of use, all available literature on ICG guided colorectal surgery and highlight areas in need of further research and discuss future perspectives. METHODS PubMed, Scopus, and Google Scholar databases were searched systematically through November 2022 for all available studies on fluorescence-guided surgery in colorectal surgery. RESULTS Available studies described ICG use in colorectal surgery for perfusion assessment, ureteral and urethral assessment, lymphatic mapping, and hepatic and peritoneal metastases assessment. Although the level of evidence is low, results are promising, especially in the role of ICG in reducing anastomotic leaks. CONCLUSIONS ICG imaging is a safe and relatively cheap imaging modality in colorectal surgery, especially for perfusion assessment. Work is underway regarding its use in lymphatic mapping, ureter identification, and the assessment of intraperitoneal metastatic disease.
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Abstract
Primary liver cancer and colorectal cancer liver metastases are among the leading causes of cancer-related mortality worldwide. Surgery is one of the main methods of treatment to achieve the best results in overall and recurrence-free survival. The main objectives in this surgery are preoperative planning, assessment of functional viability of liver parenchyma and total resection with low complication rate. Post-resection liver failure is one of the most formidable and often fatal complication following functional failure of liver remnant. Thus, preoperative assessment of liver functional reserves is a necessary step for adequate selection of patients and safe surgery. Passive liver tests, such as biochemical parameters or clinical scales, do not accurately reflect the actual functional component of liver parenchyma. The most accurate method is dynamic quantitative test of liver, such as indocyanine green clearance. The authors discuss the practical aspects of preoperative assessment of liver functional reserves using indocyanine green, as well as the concept and technical foundations of fluorescent imaging in hepatobiliary surgery.
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Affiliation(s)
- A D Kaprin
- National Medical Research Radiology Center, Obninsk, Russia
| | - S A Ivanov
- Tsyb Medical Radiology Research Center, Obninsk, Russia
| | - L O Petrov
- Tsyb Medical Radiology Research Center, Obninsk, Russia
| | - A G Isaeva
- Tsyb Medical Radiology Research Center, Obninsk, Russia
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30
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Li Z, Li X, Zhu X, Ai S, Guan W, Liu S. Tracers in Gastric Cancer Surgery. Cancers (Basel) 2022; 14:cancers14235735. [PMID: 36497216 PMCID: PMC9741333 DOI: 10.3390/cancers14235735] [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: 10/14/2022] [Revised: 11/14/2022] [Accepted: 11/18/2022] [Indexed: 11/24/2022] Open
Abstract
The treatment of gastric cancer mainly depends on radical gastrectomy. Determination of appropriate surgical margins and adequate lymph node (LN) resection are two major surgical steps that directly correlate with prognosis in gastric cancer. Due to the expanding use of minimally invasive procedures, it is no longer possible to locate tumors and LNs through touch. As an alternative, tracers have begun to enter the field due to their capacities for intraoperative visualization. Herein, we summarize the application of contemporary tracers in gastric cancer surgery, including isosulfan blue, methylene blue, patent blue, indocyanine green, carbon particles, and radioactive tracers. Their mechanisms, administration methods, detection efficiency, and challenges, as well as perspectives on them, are also outlined.
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Affiliation(s)
| | | | | | | | - Wenxian Guan
- Correspondence: (W.G.); (S.L.); Tel.: +86-25-68182222-60931 (W.G.); +86-25-68182222-60930 (S.L.)
| | - Song Liu
- Correspondence: (W.G.); (S.L.); Tel.: +86-25-68182222-60931 (W.G.); +86-25-68182222-60930 (S.L.)
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31
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Uk Bae S. Current Status and Future of Robotic Surgery for Colorectal Cancer-An English Version. J Anus Rectum Colon 2022; 6:221-230. [DOI: 10.23922/jarc.2022-047] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/21/2022] [Accepted: 08/31/2022] [Indexed: 11/05/2022] Open
Affiliation(s)
- Sung Uk Bae
- Department of Surgery, School of Medicine, Keimyung University and Dongsan Medical Center
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32
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Liao Y, Zhao J, Chen Y, Zhao B, Fang Y, Wang F, Wei C, Ma Y, Ji H, Wang D, Tang D. Mapping Lymph Node during Indocyanine Green Fluorescence-Imaging Guided Gastric Oncologic Surgery: Current Applications and Future Directions. Cancers (Basel) 2022; 14:cancers14205143. [PMID: 36291927 PMCID: PMC9601265 DOI: 10.3390/cancers14205143] [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: 09/28/2022] [Revised: 10/18/2022] [Accepted: 10/18/2022] [Indexed: 11/16/2022] Open
Abstract
Huge strides have been made in the navigation of gastric cancer surgery thanks to the improvement of intraoperative techniques. For now, the use of indocyanine green (ICG) enhanced fluorescence imaging has received promising results in detecting sentinel lymph nodes (SLNs) and tracing lymphatic drainages, which make it applicable for limited and precise lymphadenectomy. Nevertheless, issues of the lack of specificity and unpredictable false-negative lymph nodes were encountered in gastric oncologic surgery practice using ICG-enhanced fluorescence imaging (ICG-FI), which restrict its application. Here, we reviewed the current application of ICG-FI and assessed potential approaches to improving ICG-FI.
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Affiliation(s)
- Yiqun Liao
- Department of Clinical Medical College, The Yangzhou School of Clinical Medicine, Dalian Medical University, Dalian 116044, China
| | - Jiahao Zhao
- Department of Clinical Medical College, Yangzhou University, Yangzhou 225001, China
| | - Yuji Chen
- Department of Clinical Medical College, Yangzhou University, Yangzhou 225001, China
| | - Bin Zhao
- Department of Clinical Medical College, The Yangzhou School of Clinical Medicine, Dalian Medical University, Dalian 116044, China
| | - Yongkun Fang
- Department of Clinical Medical College, The Yangzhou School of Clinical Medicine, Dalian Medical University, Dalian 116044, China
| | - Fei Wang
- Department of Clinical Medical College, The Yangzhou School of Clinical Medicine, Dalian Medical University, Dalian 116044, China
| | - Chen Wei
- Department of Clinical Medical College, Yangzhou University, Yangzhou 225001, China
| | - Yichao Ma
- Department of Clinical Medical College, Yangzhou University, Yangzhou 225001, China
| | - Hao Ji
- Department of Clinical Medical College, Yangzhou University, Yangzhou 225001, China
| | - Daorong Wang
- Department of General Surgery, Northern Jiangsu People’s Hospital Affiliated to Yangzhou University, Yangzhou 225001, China
| | - Dong Tang
- Department of General Surgery, Northern Jiangsu People’s Hospital Affiliated to Yangzhou University, Yangzhou 225001, China
- Correspondence: ; Tel.: +86-189527835
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Zhang Y, Uehara T, Toyota T, Endo R, Matsubara H, Hayashi H. Stannous colloid mixed with indocyanine green as a tracer for sentinel lymph node navigation surgery. Sci Rep 2022; 12:17056. [PMID: 36224309 PMCID: PMC9556759 DOI: 10.1038/s41598-022-21420-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2022] [Accepted: 09/27/2022] [Indexed: 12/30/2022] Open
Abstract
The combined use of a vital dye and radioactive colloid reportedly performs better in detecting sentinel lymph nodes (SLNs) for cancers than the use of either of them alone. However, especially for gastric cancer, two endoscopic procedures are required to administer these two tracers, which burdens the patients and practitioners. Here we propose the use of stannous colloid (SnC) mixed with indocyanine green (ICG) as a new mixed tracer (SnC-ICG); its characteristics were investigated in vivo and in vitro to estimate its usefulness for SLN navigation. The tracers were administered to rats and the accumulation of radioactivity and/or near-infrared fluorescence were evaluated in the regional lymph nodes (LNs) using single positron emission computed tomography and near-infrared fluorescence imaging, respectively. SnC-ICG showed significantly better clearance from the injection site and better migration to primary LNs than the single administration of SnC or ICG aqueous solution. SnC-ICG demonstrated a wide particle size variability, stabilized to 1200-nm upon the addition of albumin in vitro; These properties could contribute to its behavior in vivo. The use of SnC-ICG could contribute better performance to detect SLNs for gastric cancer with less burden on both patients and medical practitioners.
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Affiliation(s)
- Yiting Zhang
- grid.136304.30000 0004 0370 1101Department of Frontier Surgery, Graduate School of Medicine, Chiba University, Inohana, Chiba-shi chuo-ku, Chiba, Japan
| | - Tomoya Uehara
- grid.136304.30000 0004 0370 1101Department of Molecular Imaging and Radiotherapy, Graduate School of Pharmaceutical Sciences, Chiba University, Inohana, Chiba-shi chuo-ku, Chiba, Japan
| | - Taro Toyota
- grid.26999.3d0000 0001 2151 536XDepartment of Graduate School of Arts and Sciences, The University of Tokyo, Komaba Meguro-ku, Tokyo, Japan
| | - Ryusuke Endo
- grid.136304.30000 0004 0370 1101Department of Medical System Engineering, Graduate School of Engineering, Chiba University, Yayoi-cho, Chiba-shi inage-ku, Chiba, Japan
| | - Hisahiro Matsubara
- grid.136304.30000 0004 0370 1101Department of Frontier Surgery, Graduate School of Medicine, Chiba University, Inohana, Chiba-shi chuo-ku, Chiba, Japan
| | - Hideki Hayashi
- grid.136304.30000 0004 0370 1101Department of Frontier Surgery, Graduate School of Medicine, Chiba University, Inohana, Chiba-shi chuo-ku, Chiba, Japan ,grid.136304.30000 0004 0370 1101Center for Frontier Medical Engineering, Chiba University, Chiba, Japan
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Kumata H, Onishi K, Takayama T, Asami K, Obara N, Sugawara H, Haga I. Efficacy of intraoperative fluorescence imaging using indocyanine green-containing gauze in identifying the appropriate dissection layer in laparoscopic intersphincteric resection: A case report. Clin Case Rep 2022; 10:e6356. [PMID: 36276903 PMCID: PMC9582673 DOI: 10.1002/ccr3.6356] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2022] [Revised: 08/26/2022] [Accepted: 08/31/2022] [Indexed: 11/05/2022] Open
Abstract
In laparoscopic intersphincteric resection, identifying the dissection layer near the anus is often difficult. We safely proceeded with it, using indocyanine green-containing gauze on the anal side to remove the internal anal sphincter with indocyanine green fluorography.
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Affiliation(s)
- Hiroyuki Kumata
- Department of SurgeryJapan Community Health Care Organization Sendai HospitalSendaiMiyagiJapan
| | - Keisuke Onishi
- Department of SurgeryYamagata City Hospital SaiseikanYamagataYamagataJapan
| | - Tetsuro Takayama
- Department of SurgeryJapan Community Health Care Organization Sendai HospitalSendaiMiyagiJapan
| | - Kengo Asami
- Department of SurgeryJapan Community Health Care Organization Sendai HospitalSendaiMiyagiJapan
| | - Noriyuki Obara
- Department of GastroenterologyJapan Community Health Care Organization Sendai HospitalSendaiMiyagiJapan
| | - Hirofumi Sugawara
- Department of SurgeryJapan Community Health Care Organization Sendai HospitalSendaiMiyagiJapan
| | - Izumi Haga
- Department of SurgeryJapan Community Health Care Organization Sendai HospitalSendaiMiyagiJapan
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Bae SU. Robotic surgery for colorectal cancer. JOURNAL OF THE KOREAN MEDICAL ASSOCIATION 2022; 65:577-585. [DOI: 10.5124/jkma.2022.65.9.577] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2022] [Accepted: 08/24/2022] [Indexed: 01/05/2025] Open
Abstract
Background: Robotic surgical systems were created partly to solve several constraints of laparoscopic surgery and to offer technical advantages. With a substantial body of evidence demonstrating its efficacy in rectal cancer treatment, robotic surgery will soon become another conventional treatment. However, further investigations and randomized trials focusing on primary endpoints are necessary to establish some advantages of robot-assisted colon surgery.Current Concepts: Da Vinci Single-Site and SP platforms (Intuitive Surgical Inc.) were developed to overcome the shortcomings of single-port laparoscopic surgery. Despite the currently insufficient evidence, it seems that the SP platform addresses several limitations of single-port transabdominal or transanal surgery. Robotic transanal minimally invasive surgery and total mesorectal excision were developed to overcome conventional platforms’ limitations, using wristed instrumentation to enhance dexterity and ergonomics. Studies on the effectiveness and viability of this novel approach are ongoing. The near-infrared fluorescence technique, real-time stereotactic navigation technology, and other surgical data platforms based on artificial intelligence incorporated into the robotic system will play an important role in improving outcomes.Discussion and Conclusion: Robotic systems for advanced colorectal cancer offer technical advantages for complex and precise surgeries. If robotic surgery costs are reduced by expanding its indications and enhancing competition among different robotic platforms, it will provide clinical benefits to more patients and reduce social healthcare costs.
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Sposito C, Maspero M, Belotti P, Simonotti N, Altomare M, Ciana P, Mazzaferro V. Indocyanine Green Fluorescence-Guided Surgery for Gastrointestinal Tumors: A Systematic Review. ANNALS OF SURGERY OPEN 2022; 3:e190. [PMID: 37601143 PMCID: PMC10431291 DOI: 10.1097/as9.0000000000000190] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2022] [Accepted: 06/28/2022] [Indexed: 11/25/2022] Open
Abstract
Objective To conduct a systematic review of the currently available literature on the use of ICG to guide surgical dissection in gastrointestinal (GI) cancer surgery. Background Real-time indocyanine green (ICG) fluorescence-guided surgery has the potential to enhance surgical outcomes by increasing patient-tailored oncological precision. Methods MEDLINE, PubMed, EMBASE, and Google Scholar were searched for publications on the use of ICG as a contrast agent in GI cancer surgery until December 2020. Perfusion studies were excluded. Quality of the studies was assessed with the Methodological Index for nonrandomized Studies or Jadad scale for randomized controlled trials. A narrative synthesis of the results was provided, with descriptive statistics when appropriate. Results Seventy-eight studies were included. ICG was used for primary tumor and metastases localization, for sentinel lymph node detection, and for lymph flow mapping. The detection rate for primary colorectal and gastric tumors was 100% after preoperative ICG endoscopic injection. For liver lesions, the detection rate after intravenous ICG infusion was 80% and up to 100% for lesions less than 8 mm from the liver surface. The detection rate for sentinel lymph nodes was 89.8% for esophageal, 98.6% for gastric, 87.4% for colorectal, and 83.3% for anal tumors, respectively. In comparative studies, ICG significantly increases the quality of D2 lymphadenectomy in oncological gastrectomy. Conclusion The use of ICG as a guiding tool for dissection in GI surgery is promising. Further evidence from high-quality studies on larger sample sizes is needed to assess whether ICG-guided surgery may become standard of care.
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Affiliation(s)
- Carlo Sposito
- From the General Surgery and Liver Transplantation Unit, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy
- Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy
| | - Marianna Maspero
- From the General Surgery and Liver Transplantation Unit, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy
- University of Milan, Milan, Italy
| | | | | | | | - Paolo Ciana
- Department of Health Sciences, Institute of Pharmacology, University of Milan, Milan, Italy
| | - Vincenzo Mazzaferro
- From the General Surgery and Liver Transplantation Unit, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy
- Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy
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Morales-Conde S, Licardie E, Alarcón I, Balla A. Indocyanine green (ICG) fluorescence guide for the use and indications in general surgery: recommendations based on the descriptive review of the literature and the analysis of experience. Cir Esp 2022; 100:534-554. [PMID: 35700889 DOI: 10.1016/j.cireng.2022.06.023] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2021] [Accepted: 11/26/2021] [Indexed: 06/15/2023]
Abstract
Indocyanine Green is a fluorescent substance visible in near-infrared light. It is useful for the identification of anatomical structures (biliary tract, ureters, parathyroid, thoracic duct), the tissues vascularization (anastomosis in colorectal, esophageal, gastric, bariatric surgery, for plasties and flaps in abdominal wall surgery, liver resection, in strangulated hernias and in intestinal ischemia), for tumor identification (liver, pancreas, adrenal glands, implants of peritoneal carcinomatosis, retroperitoneal tumors and lymphomas) and sentinel node identification and lymphatic mapping in malignant tumors (stomach, breast, colon, rectum, esophagus and skin cancer). The evidence is very encouraging, although standardization of its use and randomized studies with higher number of patients are required to obtain definitive conclusions on its use in general surgery. The aim of this literature review is to provide a guide for the use of ICG fluorescence in general surgery procedures.
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Affiliation(s)
- Salvador Morales-Conde
- Unit of Innovation in Minimally Invasive Surgery, Department of General and Digestive Surgery, University Hospital Virgen del Rocio, University of Sevilla, Sevilla, Spain; Unit of General and Digestive Surgery, Hospital Quironsalud Sagrado Corazón, Sevilla, Spain.
| | - Eugenio Licardie
- Unit of General and Digestive Surgery, Hospital Quironsalud Sagrado Corazón, Sevilla, Spain.
| | - Isaias Alarcón
- Unit of Innovation in Minimally Invasive Surgery, Department of General and Digestive Surgery, University Hospital Virgen del Rocio, University of Sevilla, Sevilla, Spain.
| | - Andrea Balla
- Unit of Innovation in Minimally Invasive Surgery, Department of General and Digestive Surgery, University Hospital Virgen del Rocio, University of Sevilla, Sevilla, Spain; UOC of General and Minimally Invasive Surgery, Hospital "San Paolo", Civitavecchia, Rome, Italy.
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Takemura N, Ito K, Inagaki F, Mihara F, Kokudo N. Added value of indocyanine green fluorescence imaging in liver surgery. Hepatobiliary Pancreat Dis Int 2022; 21:310-317. [PMID: 34953679 DOI: 10.1016/j.hbpd.2021.12.007] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/10/2021] [Accepted: 12/06/2021] [Indexed: 02/05/2023]
Abstract
Recently, indocyanine green (ICG) fluorescence imaging has been widely used as a substitute for cholangiography in hepatobiliary surgery, to detect hepatic tumors, for accurate anatomical hepatectomy, and to increase the safety and accuracy of minimally invasive (laparoscopic and robotic) hepatectomy. The clinical relevance of this method has been increasing gradually, as new procedures develop in this field. Various important roles and the latest added value of ICG fluorescence imaging in liver surgery are discussed in this report.
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Affiliation(s)
- Nobuyuki Takemura
- Department of Surgery, Hepato-Biliary Pancreatic Surgery Division, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjyuku-ku, Tokyo, 162-8655, Japan.
| | - Kyoji Ito
- Department of Surgery, Hepato-Biliary Pancreatic Surgery Division, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjyuku-ku, Tokyo, 162-8655, Japan
| | - Fuyuki Inagaki
- Department of Surgery, Hepato-Biliary Pancreatic Surgery Division, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjyuku-ku, Tokyo, 162-8655, Japan
| | - Fuminori Mihara
- Department of Surgery, Hepato-Biliary Pancreatic Surgery Division, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjyuku-ku, Tokyo, 162-8655, Japan
| | - Norihiro Kokudo
- Department of Surgery, Hepato-Biliary Pancreatic Surgery Division, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjyuku-ku, Tokyo, 162-8655, Japan
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Ekman M, Girnyi S, Marano L, Roviello F, Chand M, Diana M, Polom K. Near-Infrared Fluorescence Image-Guided Surgery in Esophageal and Gastric Cancer Operations. Surg Innov 2022; 29:540-549. [PMID: 35285305 DOI: 10.1177/15533506211073417] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/16/2025]
Abstract
BACKGROUND Near-infrared fluorescence image-guided surgery helps surgeons to see beyond the classical eye vision. Over the last few years, we have witnessed a revolution which has begun in the field of image-guided surgery. PURPOSE, AND RESEARCH DESIGN Fluorescence technology using indocyanine green (ICG) has shown promising results in many organs, and in this review article, we wanted to discuss the 6 main domains where fluorescence image-guided surgery is currently used for esophageal and gastric cancer surgery. STUDY SAMPLE AND DATA COLLECTION Visualization of lymphatic vessels, tumor localization, fluorescence angiography for anastomotic evaluation, thoracic duct visualization, tracheal blood flow analysis, and sentinel node biopsy are discussed. CONCLUSIONS It seems that this technology has already found its place in surgery. However, new possibilities and research avenues in this area will probably make it even more important in the near future.
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Affiliation(s)
- Marcin Ekman
- Department of Surgical Oncology, 37804Medical University of Gdansk, Gdansk, Poland
| | - Sergii Girnyi
- Department of Surgical Oncology, 37804Medical University of Gdansk, Gdansk, Poland
| | - Luigi Marano
- Department of Medicine, Surgery and Neurosciences, Unit of General Surgery and Surgical Oncology, 243257University of Siena, Siena, Italy
| | - Franco Roviello
- Department of Medicine, Surgery and Neurosciences, Unit of General Surgery and Surgical Oncology, 243257University of Siena, Siena, Italy
| | - Manish Chand
- Wellcome EPSRC Centre for Interventional and Surgical Sciences (WEISS), 4919University College London, London
| | - Michele Diana
- Department of Surgical Oncology, 37804Medical University of Gdansk, Gdansk, Poland
- Department of Medicine, Surgery and Neurosciences, Unit of General Surgery and Surgical Oncology, 243257University of Siena, Siena, Italy
- Wellcome EPSRC Centre for Interventional and Surgical Sciences (WEISS), 4919University College London, London
| | - Karol Polom
- Department of Surgical Oncology, 37804Medical University of Gdansk, Gdansk, Poland
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Near-Infrared Imaging Using Indocyanine Green for Laparoscopic Lateral Pelvic Lymph Node Dissection for Clinical Stage II/III Middle-Lower Rectal Cancer: A Propensity Score-Matched Cohort Study. Dis Colon Rectum 2022; 65:885-893. [PMID: 34840301 DOI: 10.1097/dcr.0000000000002156] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND The examination of the efficacy of near-infrared imaging using indocyanine green in laparoscopic lateral pelvic lymph node dissection remains insufficient. OBJECTIVE The aim of this study was to examine whether near-infrared imaging contributed to an increase in the total number of harvested lateral pelvic lymph nodes in laparoscopic lateral pelvic lymph node dissection. DESIGN This was a retrospective, multi-institutional study with propensity score matching. SETTINGS We conducted this study within the framework of the Yokohama Clinical Oncology Group in Japan. PATIENTS The study population included consecutive patients with middle-low rectal cancer (clinical stage II to III) who underwent laparoscopic lateral pelvic lymph node dissection between January 2013 and February 2018. MAIN OUTCOME MEASURES The total number of harvested lateral pelvic lymph nodes was compared in laparoscopic lateral pelvic lymph node dissection with and without near-infrared imaging. RESULTS A total of 172 eligible patients were included; 84 of these patients underwent laparoscopic surgery with near-infrared imaging. After propensity score matching, 58 patients were matched in each of the near-infrared and the non-near-infrared groups. The operation time in the near-infrared group was significantly longer than that in the non-near-infrared group (426 vs 369 min), and the amount of intraoperative blood loss in the near-infrared group was significantly smaller than that in the non-near-infrared group (13 vs 110 mL). The total number of harvested lateral pelvic lymph nodes in the near-infrared group was significantly higher than that in the non-near-infrared group (14 vs 9). There were no significant differences in the postoperative complication rates of the 2 groups. LIMITATIONS The limitations of the present study include its retrospective design. CONCLUSIONS This study revealed that laparoscopic lateral pelvic lymph node dissection combined with near-infrared imaging could increase the total number of harvested lateral pelvic lymph nodes without impairing functional preservation. See Video Abstract at http://links.lww.com/DCR/B800.This study was registered with the Japanese Clinical Trials Registry as UMIN000041372 (http://www.umin.ac.jp/ctr/index.htm).IMÁGENES CASI-INFRARROJAS UTILIZANDO VERDE DE INDOCIANINA EN LA DISECCIÓN LAPAROSCÓPICA DE GANGLIOS LINFÁTICOS PÉLVICOS LATERALES EN CASOS DE CÁNCER DE RECTO MEDIO-INFERIOR DE ESTADIO CLÍNICO II / III: ESTUDIO DE COHORTES CON PUNTUACIÓN DE PROPENSIÓNANTECEDENTES:El examen de la eficacia de las imágenes casi-infrarrojas utilizando le verde de indocianina en la disección laparoscópica de los ganglios linfáticos pélvicos laterales sigue siendo insuficiente.OBJETIVO:El objetivo de este estudio fue examinar si las imágenes casi-infrarrojas contribuyeron a un aumento en el número total de ganglios linfáticos pélvicos laterales recolectados durante su disección laparoscópica.DISEÑO:Estudio retrospectivo, multi-institucional con emparejamiento por puntuación de propensión.AJUSTES:Estudio realizado dentro el marco establecido por el Grupo de Oncología Clínica de Yokohama, Japón.PACIENTES:La población estudiada incluyó pacientes consecutivos con cáncer de recto medio-bajo (estadio clínico II a III) que se sometieron a una disección laparoscópica de los ganglios linfáticos pélvicos laterales entre enero de 2013 y febrero de 2018.PRINCIPALES RESULTADOS MEDIDAS:El número total de ganglios linfáticos pélvicos laterales extraídos se comparó en la disección laparoscópica de ganglios linfáticos pélvicos laterales con y sin imágenes casi-infrarrojas.RESULTADOS:Se incluyeron un total de 172 pacientes elegibles; 84 de estos pacientes se sometieron a cirugía laparoscópica con imágenes casi-infrarrojas. Después del emparejamiento por puntuación de propensión, 58 pacientes fueron emparejados en cada uno de los grupos de luz casi-infrarroja y los sin luz. El tiempo de operación en el grupo de luz casi-infrarroja fue significativamente más largo que en el grupo sin luz (426 frente a 369 min), y la cantidad de pérdida de sangre intraoperatoria en el grupo de luz casi-infrarroja fue significativamente menor que en el grupo sin luz (13 frente a 110 ml). El número total de ganglios linfáticos pélvicos laterales recolectados en el grupo de luz casi-infrarroja fue significativamente mayor que en el grupo sin luz (14 frente a 9). No hubo diferencias significativas en las tasas de complicaciones posoperatorias de los dos grupos.LIMITACIONES:Las limitaciones del presente estudio incluyen su diseño retrospectivo.CONCLUSIONES:Este estudio reveló que la disección laparoscópica de los ganglios linfáticos pélvicos laterales combinada con imágenes casi-infrarrojas podría aumentar el número total de ganglios linfáticos pélvicos laterales recolectados sin afectar la preservación funcional. Consulte Video Resumen en http://links.lww.com/DCR/B800. (Traducción-Dr. Xavier Delgadillo)Este estudio se registró en el Registro de Ensayos Clínicos de Japón como UMIN000041372 (http://www.umin.ac.jp/ctr/index.htm).
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Belia F, Biondi A, Agnes A, Santocchi P, Laurino A, Lorenzon L, Pezzuto R, Tirelli F, Ferri L, D’Ugo D, Persiani R. The Use of Indocyanine Green (ICG) and Near-Infrared (NIR) Fluorescence-Guided Imaging in Gastric Cancer Surgery: A Narrative Review. Front Surg 2022; 9:880773. [PMID: 35836598 PMCID: PMC9273882 DOI: 10.3389/fsurg.2022.880773] [Citation(s) in RCA: 30] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2022] [Accepted: 06/08/2022] [Indexed: 11/13/2022] Open
Abstract
Near-infrared fluorescence imaging with indocyanine green is an emerging technology gaining clinical relevance in the field of oncosurgery. In recent decades, it has also been applied in gastric cancer surgery, spreading among surgeons thanks to the diffusion of minimally invasive approaches and the related development of new optic tools. Its most relevant uses in gastric cancer surgery are sentinel node navigation surgery, lymph node mapping during lymphadenectomy, assessment of vascular anatomy, and assessment of anastomotic perfusion. There is still debate regarding the most effective application, but with relatively no collateral effects and without compromising the operative time, indocyanine green fluorescence imaging carved out a role for itself in gastric resections. This review aims to summarize the current indications and evidence for the use of this tool, including the relevant practical details such as dosages and times of administration.
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Affiliation(s)
| | - Alberto Biondi
- Università Cattolica del Sacro Cuore, Rome, Italy
- Dipartimento Di Scienze Mediche E Chirurgiche, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
- Correspondence: Alberto Biondi
| | - Annamaria Agnes
- Università Cattolica del Sacro Cuore, Rome, Italy
- Dipartimento Di Scienze Mediche E Chirurgiche, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
| | | | | | - Laura Lorenzon
- Università Cattolica del Sacro Cuore, Rome, Italy
- Dipartimento Di Scienze Mediche E Chirurgiche, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
| | - Roberto Pezzuto
- Dipartimento Di Scienze Mediche E Chirurgiche, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
| | - Flavio Tirelli
- Università Cattolica del Sacro Cuore, Rome, Italy
- Dipartimento Di Scienze Mediche E Chirurgiche, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
| | | | - Domenico D’Ugo
- Università Cattolica del Sacro Cuore, Rome, Italy
- Dipartimento Di Scienze Mediche E Chirurgiche, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
| | - Roberto Persiani
- Università Cattolica del Sacro Cuore, Rome, Italy
- Dipartimento Di Scienze Mediche E Chirurgiche, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
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Puccetti F, Cinelli L, Genova L, Battaglia S, Barbieri LA, Treppiedi E, Cossu A, Elmore U, Rosati R. Applicative Limitations of Indocyanine Green Fluorescence Assistance to Laparoscopic Lymph Node Dissection in Total Gastrectomy for Cancer. Ann Surg Oncol 2022; 29:5875-5882. [PMID: 35729291 DOI: 10.1245/s10434-022-11940-3] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2022] [Accepted: 05/08/2022] [Indexed: 11/18/2022]
Abstract
BACKGROUND Indocyanine green (ICG) fluorescence has been recently introduced as a novel imaging technique improving the accuracy of lymph node (LN) dissection in gastric cancer (GC) surgery, although procedure standardization and achievements have not been clearly defined. This study analyzed the feasibility and effectiveness of ICG-guidance for laparoscopic D2-lymphadenectomy during total gastrectomy for cancer. METHODS This study retrospectively analyzed a single-center series of patients who underwent laparoscopic total gastrectomy for cancer between April 2015 and August 2021. All patients underwent surgery with standard D2 LN dissection. Intraoperative ICG-fluorescence was institutionally implemented in April 2018 and was performed routinely afterward. Primary outcomes were LN harvest and ratio. Secondary endpoints included operative time and subgroup analysis to assess variables potentially affecting LN retrieval. RESULTS The study population included 102 patients, and ICG-fluorescence was applied in 38 (37.3%). ICG and no-ICG groups presented similar median age, gender proportions, ASA score and comorbidities (age-adjusted Charlson Comorbidity Index), body mass index, and advanced pathological stage. The median of LNs retrieved was significantly higher after the intraoperative ICG-guidance (44 vs. 32; p = 0.004), although this association was not significant after neoadjuvant therapy or among patients with positive LNs. Lymph node ratio and operative time were not significantly impacted by ICG fluorescence. Multivariate analysis identified the ICG-assistance as the only independent determinant for LN harvest (p = 0.029). CONCLUSIONS ICG-guidance contributes to a significantly wider LN retrieval after laparoscopic D2-lymphadenectomy during total gastrectomy for cancer. However, neoadjuvant therapy and positive LN stage appeared to limit the procedural effectiveness to ICG-assisted LN identification.
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Affiliation(s)
- Francesco Puccetti
- Department of Gastrointestinal Surgery, San Raffaele Research Hospital, 20132, Milan, Italy.,Faculty of Medicine and Surgery, Vita-Salute San Raffaele University, 20132, Milan, Italy
| | - Lorenzo Cinelli
- Department of Gastrointestinal Surgery, San Raffaele Research Hospital, 20132, Milan, Italy
| | - Luana Genova
- Department of Gastrointestinal Surgery, San Raffaele Research Hospital, 20132, Milan, Italy
| | - Silvia Battaglia
- Department of Gastrointestinal Surgery, San Raffaele Research Hospital, 20132, Milan, Italy
| | - Lavinia A Barbieri
- Department of Gastrointestinal Surgery, San Raffaele Research Hospital, 20132, Milan, Italy
| | - Elio Treppiedi
- Department of Gastrointestinal Surgery, San Raffaele Research Hospital, 20132, Milan, Italy
| | - Andrea Cossu
- Department of Gastrointestinal Surgery, San Raffaele Research Hospital, 20132, Milan, Italy
| | - Ugo Elmore
- Department of Gastrointestinal Surgery, San Raffaele Research Hospital, 20132, Milan, Italy. .,Faculty of Medicine and Surgery, Vita-Salute San Raffaele University, 20132, Milan, Italy.
| | - Riccardo Rosati
- Department of Gastrointestinal Surgery, San Raffaele Research Hospital, 20132, Milan, Italy.,Faculty of Medicine and Surgery, Vita-Salute San Raffaele University, 20132, Milan, Italy
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Guía de uso e indicaciones de la fluorescencia con verde de indocianina (ICG) en cirugía general: recomendaciones basadas en la revisión descriptiva de la literatura y el análisis de la experiencia. Cir Esp 2022. [DOI: 10.1016/j.ciresp.2021.11.018] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
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Kurochkin MA, German SV, Abalymov A, Vorontsov DА, Gorin DA, Novoselova MV. Sentinel lymph node detection by combining nonradioactive techniques with contrast agents: State of the art and prospects. JOURNAL OF BIOPHOTONICS 2022; 15:e202100149. [PMID: 34514735 DOI: 10.1002/jbio.202100149] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/06/2021] [Revised: 08/21/2021] [Accepted: 09/09/2021] [Indexed: 06/13/2023]
Abstract
The status of sentinel lymph nodes (SLNs) has a substantial prognostic value because these nodes are the first place where cancer cells accumulate along their spreading route. Routine SLN biopsy ("gold standard") involves peritumoral injections of radiopharmaceuticals, such as technetium-99m, which has obvious disadvantages. This review examines the methods used as "gold standard" analogs to diagnose SLNs. Nonradioactive preoperative and intraoperative methods of SLN detection are analyzed. Promising photonic tools for SLNs detection are reviewed, including NIR-I/NIR-II fluorescence imaging, photoswitching dyes for SLN detection, in vivo photoacoustic detection, imaging and biopsy of SLNs. Also are discussed methods of SLN detection by magnetic resonance imaging, ultrasonic imaging systems including as combined with photoacoustic imaging, and methods based on the magnetometer-aided detection of superparamagnetic nanoparticles. The advantages and disadvantages of nonradioactive SLN-detection methods are shown. The review concludes with prospects for the use of conservative diagnostic methods in combination with photonic tools.
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Affiliation(s)
| | - Sergey V German
- Skolkovo Institute of Science and Technology, Moscow, Russia
- Institute of Spectroscopy of the Russian Academy of Sciences, Moscow, Russia
| | | | - Dmitry А Vorontsov
- State Budgetary Institution of Health Care of Nizhny Novgorod "Nizhny Novgorod Regional Clinical Oncological Dispensary", Nizhny Novgorod, Russia
| | - Dmitry A Gorin
- Skolkovo Institute of Science and Technology, Moscow, Russia
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Ebihara Y, Li L, Noji T, Kurashima Y, Murakami S, Shichinohe T, Hirano S. A novel laparoscopic near-infrared fluorescence spectrum system with indocyanine green fluorescence overcomes limitations of near-infrared fluorescence image-guided surgery. J Minim Access Surg 2022; 18:125-128. [PMID: 35017402 PMCID: PMC8830575 DOI: 10.4103/jmas.jmas_165_20] [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: 08/04/2020] [Revised: 11/18/2020] [Accepted: 01/08/2021] [Indexed: 11/09/2022] Open
Abstract
BACKGROUND Near-infrared (NIR) fluorescence image-guided surgery (FIGS) introduces a revolutionary new approach to address this basic challenge in minimally invasive surgery. However, current FIGS systems have some limitations - the infrared rays cannot detect and visualise thick tissues with low concentrations of the fluorescent agent. We established a novel laparoscopic fluorescence spectrum (LFS) system using indocyanine green (ICG) fluorescence to overcome these limitations. MATERIALS AND METHODS Bovine serum albumin (BSA) was conjugated to ICG, and the mixtures were serially diluted at 5 × 10-8-5 × 10-1 mg/mL. We used the LFS system and a NIR camera system (NLS; SHINKO OPTICAL CO., LTD Tokyo, Japan) to determine the optical dilution for the fluorescence detection. BSA was conjugated to ICG (5.0 × 10-2 mg/mL) and used to coat the clips. We attempted to identify the fluorescence-coated clip from the serosal side of the cadaveric porcine stomach tissues using the LFS system and the NIR camera system. We measured the depth of the cadaveric porcine stomach wall at the thickest part that could be confirmed. RESULTS We could not visualise fluorescence concentrations <2.5 × 10-3 mg/mL using the NIR camera system. The spectrum was detected at a concentration <2.5 × 10-3 mg/mL. We were able to identify the spectrum of ICG (829 nm) to a 13-mm depth of cadaveric porcine stomach wall by using the LFS system but could not identify the same with the NIR camera system regardless of wall thickness. CONCLUSIONS The novel LFS system with NIR fluorescence imaging in this ex vivo and cadaveric porcine model was confirmed useful at deeper depths and lower concentrations. Based on these findings, we anticipate that the LFS system can be integrated and routinely used in minimally invasive surgery.
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Affiliation(s)
- Yuma Ebihara
- Department of Gastroenterological Surgery II, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido, Japan
- Division of Minimally Invasive Surgery, Hokkaido University Hospital, Sapporo, Hokkaido, Japan
| | - Liming Li
- Department of Bio-material, Graduate School of Photonics Science, Chitose Institute of Science and Technology, Chitose, Hokkaido, Japan
| | - Takehiro Noji
- Department of Gastroenterological Surgery II, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido, Japan
| | - Yo Kurashima
- Department of Gastroenterological Surgery II, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido, Japan
| | - Soichi Murakami
- Department of Gastroenterological Surgery II, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido, Japan
| | - Toshiaki Shichinohe
- Department of Gastroenterological Surgery II, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido, Japan
| | - Satoshi Hirano
- Department of Gastroenterological Surgery II, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido, Japan
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Han YR, Lee DS, Lee SB, Jeon HJ, Lee S, Sung SE, Lee CH, Cho SJ, Kim KS, Kim DS, Jeon YH. Discovery of novel phenaleno isoquinolinium-based fluorescence imaging agents for sentinel lymph node mapping. J Mater Chem B 2021; 9:9946-9950. [PMID: 34852032 DOI: 10.1039/d1tb02146j] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
Fluorescence imaging agents have recently received huge attention due to their important role in disease diagnostics. However, the intrinsic problems of these probes, such as complex synthetic routes and high molecular weight, remain challenging. Here, we developed novel phenaleno isoquinolinium-based fluorescent agents, Medical Fluorophores 37-41 (MF37-41), applicable to the quantitative and sensitive detection of sentinel lymph nodes (SLNs). These imaging agents showed no adverse effects on the proliferation of immune and normal cells and did not induce in vivo toxicity. In vivo fluorescence lifetime imaging demonstrated the accumulation of phenaleno isoquinolinium salts in the SLNs of nude mice within 15 min postinjection, consistent with our biodistribution findings. These results suggest that phenaleno isoquinolinium salts are feasible fluorescence imaging agents that can be used as potential lymphatic tracers.
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Affiliation(s)
- Ye Ri Han
- New Drug Development Center Daegu-Gyeongbuk Medical Innovation Foundation Daegu 700-721, South Korea
| | - Da-Sol Lee
- Laboratory Animal Center Daegu-Gyeongbuk Medical Innovation Foundation Daegu 700-721, South Korea.
| | - Sang Bong Lee
- Vaccine Commercialization Center, Gyeongbuk Institute for Bio industry, 88 Saneopdanji-gil, pungsan-eup, Andong-si, Gyeongbuk, 33618, South Korea
| | - Hui-Jeon Jeon
- New Drug Development Center Daegu-Gyeongbuk Medical Innovation Foundation Daegu 700-721, South Korea
| | - Sijoon Lee
- Laboratory Animal Center Daegu-Gyeongbuk Medical Innovation Foundation Daegu 700-721, South Korea.
| | - Soo-Eun Sung
- Laboratory Animal Center Daegu-Gyeongbuk Medical Innovation Foundation Daegu 700-721, South Korea.
| | - Chang-Hee Lee
- Department of Chemistry, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul 03722, Republic of Korea
| | - Sung Jin Cho
- New Drug Development Center Daegu-Gyeongbuk Medical Innovation Foundation Daegu 700-721, South Korea
| | - Kil Soo Kim
- Laboratory Animal Center Daegu-Gyeongbuk Medical Innovation Foundation Daegu 700-721, South Korea. .,College of Veterinary Medicine, Kyungpook National University, Daegu 41566, South Korea
| | - Dong-Su Kim
- Therapeutics and Biotechnology Division, Korea Research Institute of Chemical Technology, 141 Gajeongro, Yuseong, Daejeon 31414, South Korea.
| | - Yong Hyun Jeon
- Laboratory Animal Center Daegu-Gyeongbuk Medical Innovation Foundation Daegu 700-721, South Korea. .,Leading-edge Research Center for Drug Discovery and Development for Diabetes and Metabolic Disease, Kyungpook National University Hospital, Daegu, South Korea
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Kinami S, Nakamura N, Miyashita T, Kitakata H, Fushida S, Fujimura T, Iida Y, Inaki N, Ito T, Takamura H. Life prognosis of sentinel node navigation surgery for early-stage gastric cancer: Outcome of lymphatic basin dissection. World J Gastroenterol 2021; 27:8010-8030. [PMID: 35046627 PMCID: PMC8678813 DOI: 10.3748/wjg.v27.i46.8010] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/20/2021] [Revised: 06/28/2021] [Accepted: 11/29/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Lymphatic basin dissection is a sentinel node biopsy method that is specific for gastric cancer. In this method, the dyed lymphatic system is dissected en bloc, and sentinel nodes are identified at the back table (ex vivo). Even with lymphatic basin dissection, blood flow to the residual stomach can be preserved, and function-preserving curative gastrectomy can be performed. The oncological safety of function-preserving curative gastrectomy combined with lymphatic basin dissection has not yet been fully investigated. We hypothesized that the oncological safety of sentinel node navigation surgery (SNNS) is not inferior to that of the guidelines. AIM To investigate the life prognosis of SNNS for gastric cancer in comparison with guidelines surgery. METHODS This was a retrospective cohort study. Patients were selected from gastric cancer patients who underwent sentinel node biopsy from April 1999 to March 2016. Patients from April 1999 to August 2008 were from the Department of Surgery II, Kanazawa University Hospital, and patients from August 2009 to March 2016 were from the Department of Surgical Oncology, Kanazawa Medical University Hospital. Patients who were diagnosed with gastric cancer, which was preoperatively diagnosed as superficial type (type 0), 5 cm or less in length, clinical T1-2 and node negative, and underwent various gastrectomies guided by sentinel node navigation were retrospectively collected. The overall survival (OS) and relapse-free survival (RFS) of these patients (SNNS group) were investigated. Patients with gastric cancer of the same stage and who underwent guidelines gastrectomy with standard nodal dissection were also selected as the control group. RESULTS A total of 239 patients in the SNNS group and 423 patients in the control group were included. Pathological nodal metastasis was observed in 10.5% and 10.4% of the SNNS and control groups, respectively. The diagnostic abilities of sentinel node biopsy were 84% and 98.6% for sensitivity and accuracy, respectively. In the SNNS group, 81.6% of patients underwent modified gastrectomy or function-preserving curative gastrectomy with lymphatic basin dissection, in which the extent of nodal dissection was further reduced compared to the guidelines. The OS rate in the SNNS group was 96.8% at 5 years and was significantly better than 91.3% in the control group (P = 0.0014). The RFS rates were equal in both groups. After propensity score matching, there were 231 patients in both groups, and the cumulative recurrence rate was 0.43% at 5 years in the SNNS group and 1.30% in the control group, which was not statistically different. CONCLUSION The oncological safety of patients who undergo gastrectomy guided by sentinel node navigation is not inferior to that of the guidelines surgery.
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Affiliation(s)
- Shinichi Kinami
- Department of Surgical Oncology, Kanazawa Medical University, Kahoku 920-0293, Ishikawa, Japan
| | - Naohiko Nakamura
- Department of Surgical Oncology, Kanazawa Medical University, Kahoku 920-0293, Ishikawa, Japan
| | - Tomoharu Miyashita
- Department of Surgical Oncology, Kanazawa Medical University, Kahoku 920-0293, Ishikawa, Japan
| | - Hidekazu Kitakata
- Department of Gastroenterological Endoscopy, Kanazawa Medical University, Kahoku 920-0293, Ishikawa, Japan
| | - Sachio Fushida
- Department of Gastrointestinal Surgery, Kanazawa University, Kanazawa 920-8641, Ishikawa, Japan
| | - Takashi Fujimura
- Department of Surgery, Toyama City Hospital, Toyama 939-8511, Toyama, Japan
| | - Yasuo Iida
- Department of Mathematics, Division of General Education, Kanazawa Medical University, Kahoku 920-0293, Ishikawa, Japan
| | - Noriyuki Inaki
- Department of Gastrointestinal Surgery, Kanazawa University, Kanazawa 920-8641, Ishikawa, Japan
| | - Toru Ito
- Department of Gastroenterological Endoscopy, Kanazawa Medical University, Kahoku 920-0293, Ishikawa, Japan
| | - Hiroyuki Takamura
- Department of Surgical Oncology, Kanazawa Medical University, Kahoku 920-0293, Ishikawa, Japan
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Turner MA, Lwin TM, Amirfakhri S, Nishino H, Hoffman RM, Yazaki PJ, Bouvet M. The Use of Fluorescent Anti-CEA Antibodies to Label, Resect and Treat Cancers: A Review. Biomolecules 2021; 11:1819. [PMID: 34944463 PMCID: PMC8699160 DOI: 10.3390/biom11121819] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2021] [Revised: 11/21/2021] [Accepted: 11/26/2021] [Indexed: 02/07/2023] Open
Abstract
A major barrier to the diagnosis and effective treatment of solid-tumor cancers is the difficulty in detection and visualization of tumor margins in primary and metastatic disease. The use of fluorescence can augment the surgeon's ability to detect cancer and aid in its resection. Several cancer types express carcinoembryonic antigen (CEA) including colorectal, pancreatic and gastric cancer. Antibodies to CEA have been developed and tagged with near-infrared fluorescent dyes. This review article surveyed the use of CEA antibodies conjugated to fluorescent probes for in vivo studies since 1990. PubMed and Google Scholar databases were queried, and 900 titles and abstracts were screened. Fifty-nine entries were identified as possibly meeting inclusion/exclusion criteria and were reviewed in full. Forty articles were included in the review and their citations were screened for additional entries. A total of 44 articles were included in the final review. The use of fluorescent anti-CEA antibodies has been shown to improve detection and resection of tumors in both murine models and clinically. The cumulative results indicate that fluorescent-conjugated anti-CEA antibodies have important potential to improve cancer diagnosis and surgery. In an emerging technology, anti-CEA fluorescent antibodies have also been successfully used for photoimmunotherapy treatment for cancer.
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Affiliation(s)
- Michael A. Turner
- VA San Diego Healthcare System, La Jolla, CA 92161, USA; (M.A.T.); (S.A.); (H.N.); (R.M.H.)
- Division of Surgical Oncology, Department of Surgery, University of California San Diego, La Jolla, CA 92037, USA
| | | | - Siamak Amirfakhri
- VA San Diego Healthcare System, La Jolla, CA 92161, USA; (M.A.T.); (S.A.); (H.N.); (R.M.H.)
- Division of Surgical Oncology, Department of Surgery, University of California San Diego, La Jolla, CA 92037, USA
| | - Hiroto Nishino
- VA San Diego Healthcare System, La Jolla, CA 92161, USA; (M.A.T.); (S.A.); (H.N.); (R.M.H.)
- Division of Surgical Oncology, Department of Surgery, University of California San Diego, La Jolla, CA 92037, USA
| | - Robert M. Hoffman
- VA San Diego Healthcare System, La Jolla, CA 92161, USA; (M.A.T.); (S.A.); (H.N.); (R.M.H.)
- Division of Surgical Oncology, Department of Surgery, University of California San Diego, La Jolla, CA 92037, USA
- AntiCancer Inc., San Diego, CA 92111, USA
| | - Paul J. Yazaki
- Department of Immunology and Theranostics, Beckman Research Institute, City of Hope, Duarte, CA 91010, USA;
| | - Michael Bouvet
- VA San Diego Healthcare System, La Jolla, CA 92161, USA; (M.A.T.); (S.A.); (H.N.); (R.M.H.)
- Division of Surgical Oncology, Department of Surgery, University of California San Diego, La Jolla, CA 92037, USA
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Martínez-López E, Martínez-Pérez A, Navarro-Martínez S, Sebastián-Tomás JC, de'Angelis N, García-Granero E. Real-time fluorescence image-guided gastrointestinal oncologic surgery: Towards a new era. World J Gastrointest Oncol 2021; 13:1029-1042. [PMID: 34616510 PMCID: PMC8465438 DOI: 10.4251/wjgo.v13.i9.1029] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/22/2021] [Revised: 06/14/2021] [Accepted: 07/27/2021] [Indexed: 02/06/2023] Open
Abstract
Technological improvements are crucial in the evolution of surgery. Real-time fluorescence-guided surgery (FGS) has spread worldwide, mainly because of its usefulness during the intraoperative decision-making processes. The success of any gastrointestinal oncologic resection is based on the anatomical identification of the primary tumor and its regional lymph nodes. FGS allows also to evaluate the blood perfusion at the gastrointestinal stumps after colorectal or esophageal resections. Therefore, a reduction on the anastomotic leak rates has been postulated as one of the foreseeable benefits provided by the use of FGS in these procedures. Although the use of fluorescence in lymph node detection was initially described in breast cancer surgery, the technique is currently applied in gastric or splenic flexure cancers, as they both present complex and variable lymphatic drainages. FGS allows also to perform intraoperative lymphograms or sentinel lymph node biopsies. New applications of FGS are being developed to assist in the detection of peritoneal metastases or in the evaluation of the tumor resection margins. The present review aims to provide a general overview of the current status of real-time FGS in gastrointestinal oncologic surgery. We put a special focus on the different applications of FGS, discussing the main findings and limitations found in the contemporary literature and also the promising near future applications.
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Affiliation(s)
- Elías Martínez-López
- Department of Surgery, University of Valencia, Valencia 46010, Spain
- Department of General and Digestive Surgery, Hospital Universitario Doctor Peset, Valencia 46017, Spain
| | - Aleix Martínez-Pérez
- Faculty of Health Sciences, Valencian International University, Valencia 46002, Spain
- Minimally Invasive and Robotic Digestive Surgery Unit, Miulli Hospital, Acquaviva delle Fonti 70021, Italy
| | - Sergio Navarro-Martínez
- Department of General and Digestive Surgery, Hospital Universitario Doctor Peset, Valencia 46017, Spain
| | - Juan Carlos Sebastián-Tomás
- Department of Surgery, University of Valencia, Valencia 46010, Spain
- Department of General and Digestive Surgery, Hospital Universitario Doctor Peset, Valencia 46017, Spain
| | - Nicola de'Angelis
- Minimally Invasive and Robotic Digestive Surgery Unit, Miulli Hospital, Acquaviva delle Fonti 70021, Italy
| | - Eduardo García-Granero
- Department of Surgery, University of Valencia, Valencia 46010, Spain
- Department of General and Digestive Surgery, Hospital Universitario y Politécnico La Fe, Valencia 46026, Spain
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He Y, Khan T, Kryza T, Jones ML, Goh JB, Lyons NJ, Pearce LA, Lee MD, Gough M, Rogers R, Davies CM, Gilks CB, Hodgkinson T, Lourie R, Barry SC, Perrin LC, Williams CC, Puttick S, Adams TE, Munro TP, Hooper JD, Chetty N. Preclinical Evaluation of a Fluorescent Probe Targeting Receptor CDCP1 for Identification of Ovarian Cancer. Mol Pharm 2021; 18:3464-3474. [PMID: 34448393 DOI: 10.1021/acs.molpharmaceut.1c00401] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
Optimal cytoreduction for ovarian cancer is often challenging because of aggressive tumor biology and advanced stage. It is a critical issue since the extent of residual disease after surgery is the key predictor of ovarian cancer patient survival. For a limited number of cancers, fluorescence-guided surgery has emerged as an effective aid for tumor delineation and effective cytoreduction. The intravenously administered fluorescent agent, most commonly indocyanine green (ICG), accumulates preferentially in tumors, which are visualized under a fluorescent light source to aid surgery. Insufficient tumor specificity has limited the broad application of these agents in surgical oncology including for ovarian cancer. In this study, we developed a novel tumor-selective fluorescent agent by chemically linking ICG to mouse monoclonal antibody 10D7 that specifically recognizes an ovarian cancer-enriched cell surface receptor, CUB-domain-containing protein 1 (CDCP1). 10D7ICG has high affinity for purified recombinant CDCP1 and CDCP1 that is located on the surface of ovarian cancer cells in vitro and in vivo. Our results show that intravenously administered 10D7ICG accumulates preferentially in ovarian cancer, permitting visualization of xenograft tumors in mice. The data suggest CDCP1 as a rational target for tumor-specific fluorescence-guided surgery for ovarian cancer.
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Affiliation(s)
- Yaowu He
- Mater Research Institute - The University of Queensland, Translational Research Institute, 37 Kent Street, Woolloongabba, QLD 4102, Australia
| | - Tashbib Khan
- Mater Research Institute - The University of Queensland, Translational Research Institute, 37 Kent Street, Woolloongabba, QLD 4102, Australia
| | - Thomas Kryza
- Mater Research Institute - The University of Queensland, Translational Research Institute, 37 Kent Street, Woolloongabba, QLD 4102, Australia
| | - Martina L Jones
- Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, Brisbane, QLD 4072, Australia
| | - Justin B Goh
- Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, Brisbane, QLD 4072, Australia
| | - Nicholas J Lyons
- Mater Research Institute - The University of Queensland, Translational Research Institute, 37 Kent Street, Woolloongabba, QLD 4102, Australia
| | | | | | - Madeline Gough
- Mater Research Institute - The University of Queensland, Translational Research Institute, 37 Kent Street, Woolloongabba, QLD 4102, Australia
| | - Rebecca Rogers
- Mater Research Institute - The University of Queensland, Translational Research Institute, 37 Kent Street, Woolloongabba, QLD 4102, Australia.,Mater Health Services, South Brisbane, QLD 4101, Australia
| | - Claire M Davies
- Mater Research Institute - The University of Queensland, Translational Research Institute, 37 Kent Street, Woolloongabba, QLD 4102, Australia.,Mater Health Services, South Brisbane, QLD 4101, Australia
| | - C Blake Gilks
- Department of Pathology and Laboratory Medicine, Vancouver General Hospital, University of British Columbia, Vancouver, BC V6T 2B5, Canada
| | | | - Rohan Lourie
- Mater Health Services, South Brisbane, QLD 4101, Australia
| | - Sinead C Barry
- Mater Health Services, South Brisbane, QLD 4101, Australia
| | - Lewis C Perrin
- Mater Health Services, South Brisbane, QLD 4101, Australia
| | | | | | | | - Trent P Munro
- Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, Brisbane, QLD 4072, Australia
| | - John D Hooper
- Mater Research Institute - The University of Queensland, Translational Research Institute, 37 Kent Street, Woolloongabba, QLD 4102, Australia
| | - Naven Chetty
- Mater Health Services, South Brisbane, QLD 4101, Australia
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