Fluorescent Clips Research Articles

Utility of near-infrared fluorescent clip for the robot-assisted gastrectomy: Report of 2 cases (case series)

Introduction and importanceThe 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 presentationCase 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 discussionThe 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. ConclusionBased on the results of the above two cases, ZEOCLIP FS is influential in determining the tumor's location and the resection line.

Robot-assisted Surgery for Gastrointestinal Cancer Using Indocyanine Green Conjugated Endoscopic Marking Clip Under Firefly Fluorescence Imaging.

Intraoperative identification of the cancer location is often difficult during robot-assisted surgery, especially in early stage cancers. This study aimed to investigate the feasibility and accuracy of a novel endoscopic clip emitting near-infrared (NIR) fluorescence during robot-assisted surgery for gastrointestinal cancer. Preoperative placement of endoscopic marking clips equipped with NIR fluorescent resin was performed to determine the resection margins in six patients with gastrointestinal cancer. During robot-assisted surgery, a NIR fluorescence imaging system was used to detect the fluorescence. The evaluation examined whether fluorescence from the clips was visualized during robot-assisted surgery. The NIR fluorescent signals emitted from the clips were successfully detected in all six patients from the serosal surfaces, resulting in the quick and accurate identification of the resection line. There were no significant differences in age, sex, or body mass index between the patients in whom we could detect NIR fluorescence. This novel NIR fluorescent clip is a promising diagnostic tool for accurately detecting tumor locations during robot-assisted surgery for gastrointestinal cancer.

Indocyanine-coated fluorescent clips for localization of gastrointestinal tumors

Indocyanine-coated fluorescent clips for localization of gastrointestinal tumors

Fluorescence guidance using near-infrared fluorescent clips in robotic rectal surgery: a case series

PurposeTattoo markings are often used as preoperative markers for colorectal cancer. However, scattered ink markings adversely affect tumor site recognition intraoperatively; therefore, interventions for rectal cancer may lead to an inaccurate distal resection margin (DRM) and incomplete total mesorectal excision (TME). This is the first case series of fluorescence-guided robotic rectal surgery in which near-infrared fluorescence clips (NIRFCs) were used to localize rectal cancer lesions.MethodsWe enrolled 20 consecutive patients who underwent robotic surgery for rectal cancer between December 2022 and December 2023 in the current study. The primary endpoints were the rate of intraoperative clip detection and its usefulness for marking the tumor site. Secondary endpoints were oncological assessments, including DRM and the number of lymph nodes.ResultsClip locations were confirmed in 17 of 20 (85%) patients. NIRFCs were not detected in 3 out of 7 patients who underwent preoperative chemoradiation therapy. No adverse events, including bleeding or perforation, were observed at the time of clipping, and no clips were lost. The median DRM was 55 mm (range, 22–86 mm) for rectosigmoid (Rs), 33 mm (range, 16–60 mm) for upper rectum (Ra), and 20 mm (range, 17–30 mm) for low rectum (Rb). The median number of lymph nodes was 13 (range, 10–21).ConclusionThe rate of intraoperative clip detection, oncological assessment, including DRM, and the number of lymph nodes indicate that the utility of fluorescence-guided methods with NIRFCs is feasible for rectal cancer.

Use of inducible and limiting fluorescence in laparoscopic endoscopic cooperative surgery

Video 1Demonstration of the special use of the near-infrared fluorescent clip in laparoscopic endoscopic cooperative surgery.

Preoperative fluorescent clip marking vs. India ink tattooing for tumor identification during colorectal surgery.

Identifying tumor location is important in colorectal tumor resection. Preoperative endoscopic India ink marking is a widespread practice, but local injection of ink is an unstable procedure. Although it is often invisible, the ink may be sprayed into the peritoneal cavity and contaminate the surgical field. At our hospital, we introduced fluorescent clip marking (FCM) using the Zeoclip FS®, an endoscopic clip developed using near-infrared fluorescent resin. We tested the usefulness of FCM by retrospectively comparing cases in which FCM was used with cases in which conventional ink marking was used. We enrolled 305 patients with colorectal tumors who underwent colorectal surgery after preoperative marking from January 2017 to April 2022. We classified the patients into the FCM group (86 patients) and the India ink tattoo group (219 patients). Endoscopic marking was completed in the FCM group by the day before surgery, and fluorescence was evaluated during surgery with a fluorescent laparoscopic system. Patient backgrounds, marking visibility, adverse effects, and early postoperative results were retrospectively compared between groups. Marking was visually confirmed in 80 patients in the FCM group (93.02%) and in 166 patients in the India ink tattoo group (75.80%) (p = 0.0006). In the group with India ink tattoos, contamination of the surgical field was observed in seven cases (3.20%). No adverse events were observed in the FCM group. In colorectal surgery, FCM provides better visibility than the conventional India ink tattooing method and is a simple and safe marking method. Examination of fluorescence navigation for laparoscopic colorectal cancer surgery. Research Ethics Committee of the Kawaguchi Municipal Medical Center (Saitama, Japan) approval number: 2020-3. https://kawaguchi-mmc.org/wp-content/uploads/clinicalresearch-r02.pdf .

Efficacy and Safety of Gastrointestinal Tumour Site Marking with da Vinci-Compatible Near-Infrared Fluorescent Clips: A Case Series

BackgroundThe conventional near-infrared fluorescent clip (NIRFC) ZEOCLIP FS® has been used successfully in marking tumour sites during laparoscopic surgeries. However, this clip is difficult to observe with the Firefly imaging system equipped with the da Vinci® surgical system. We have been involved in the modification of ZEOCLIP FS® and development of da Vinci-compatible NIRFC. This is the first prospective single-centre case series study verifying the usefulness and safety of the da Vinci-compatible NIRFC.MethodsTwenty-eight consecutive patients undergoing da Vinci®-assisted surgery for gastrointestinal cancer (16 gastric, 4 oesophageal, and 8 rectal cases) between May 2021 and May 2022 were enrolled.ResultsTumour location was identified by the da Vinci-compatible NIRFCs in 21 of 28 (75%) patients, which involved 12 gastric (75%), 4 oesophageal (100%), and 5 rectal (62%) cancer cases. No adverse events were observed.ConclusionTumour site marking with da Vinci-compatible NIRFC was feasible in 28 patients enrolled in this study. Further studies are warranted to substantiate the safety and improve the recognition rate.

Effectiveness of fluorescence-guided methods using near-infrared fluorescent clips of robotic colorectal surgery: a case report

BackgroundThis is the first report on the application of the Da Vinci-compatible near-infrared fluorescent clips (NIRFCs) as tumor markers to localize colorectal cancer lesions during robotic surgery. In laparoscopic and robotic colorectal surgeries, the accuracy of tumor marking is a critical issue that remains unresolved. This study aimed to determine the accuracy of NIRFCs in localizing tumors for intestinal resection. Indocyanine green (ICG) was also used to verify the feasibility of safely performing an anastomosis.Case presentationA patient diagnosed with rectal cancer was scheduled to undergo a robot-assisted high anterior resection. During colonoscopy 1 day prior to the surgery, four Da Vinci-compatible NIRFCs were placed intraluminally 90° around the lesion. The locations of the Da Vinci-compatible NIRFCs were confirmed using firefly technology, and ICG staining was performed before cutting the oral side of the tumor. The locations of the Da Vinci-compatible NIRFCs and the intestinal resection line were confirmed. Moreover, sufficient margins were obtained.ConclusionsIn robotic colorectal surgery, fluorescence guidance with firefly technology offers two advantages. First, it has an oncological advantage, because marking with the Da Vinci-compatible NIRFCs allows for real-time monitoring of the lesion location. This enables sufficient intestinal resection by grasping the lesion precisely. Second, it reduces the risk of postoperative complications, because ICG evaluation with firefly technology prevents postoperative anastomotic leakage. Fluorescence guidance in robot-assisted surgery is useful. In the future, the application of this technique should be evaluated for lower rectal cancer.

Intraoperative Tumor Identification During Laparoscopic Distal Gastrectomy: a Novel Fluorescent Clip Marking Versus Metal Clip Marking and Intraoperative Gastroscope

BackgroundIn complete laparoscopic distal gastrectomy, the gastric resection line is difficult to determine due to a lack of tactile sensation. The use of intraoperative gastroscopy and intraoperative radiography has been reported, but the burden on personnel and technical complexity present impediments. In our department, based on lesion extent determined with preoperative gastroscopy, a fluorescent clip is used to mark the oral side of the lesion, which is resected after confirmation with a fluorescent laparoscopic system. In this study, we investigated the efficacy of fluorescent clip marking (FCM) in achieving an accurate resection line and reducing the operative time. MethodsFifty-six patients with gastric cancer who underwent complete laparoscopic distal gastrectomy from January 2018 to March 2021 were divided into two groups: the FCM group (n = 32) and the conventional metal clip marking and intraoperative gastroscopy (MCMG) group (n = 24). Short-term outcomes, including the resection margins, gastric resection time, and operative time, were compared and examined. ResultsThe fluorescent clips were visible in all cases, and all stumps were negative according to permanent preparations. The operative times for FCM and MCMG were 350 (216–533) vs. 373.5 (258–651) min, respectively, with no significant difference (p = 0.316), while the gastric resection times were 636.5 (321–2572) vs. 1457.5 (843–4973) s, respectively, and were significantly shorter in the FCM group (p < 0.0001). ConclusionsFCM shortened the gastric resection time and could possibly shorten the operative time. FCM is feasible and safe and can potentially be used as a tumor-marking agent to determine accurate surgical resection lines. Clinical Trial RegistrationExamination of Gastric Cancer, Research Ethics Committee of the Kawaguchi Municipal Medical Centre (Saitama, Japan), approval number: 2019-33. https://kawaguchi-mmc.org/wp-content/uploads/clinicalresearch-r02.pdf

Usefulness of preoperative site marking with an indocyanine green fluorescent clip for gastrointestinal stromal tumor.

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Intraoperative Tumor Localization of Early Gastric Cancers.

Recently, endoscopic screening systems have enabled the diagnosis of gastric cancer in the early stages. Early gastric cancer (EGC) is typically characterized by a shallow invasion depth and small size, which can hinder localization of EGC tumors during laparoscopic surgery. Here, we review nine recently reported tumor localization methods for the laparoscopic resection of EGCs. Preoperative dye or blood tattooing has the disadvantage of spreading. Preoperative 3-dimensional computed tomography reconstruction is not performed in real time during laparoscopic gastrectomy. Thus, they are considered to have a low accuracy. Intraoperative portable abdominal radiography and intraoperative laparoscopic ultrasonography methods can provide real-time feedback, but these methods require expertise, and it can be difficult to define the clips in some gastric regions. Despite a few limitations, intraoperative gastrofibroscopy provides real-time feedback with high accuracy. The detection system using an endoscopic magnetic marking clip, fluorescent clip, and radio-frequency identification detection system clip is considered highly accurate and provides real-time feedback; we expect a commercial version of this setup to be available in the near future. However, there is not yet an easy method for accurate real-time detection. We hope that improved devices will soon be developed and used in clinical settings.

Usefulness of Preoperative Endoscopic Fluorescent Clip Marking in Laparoscopic Gastrointestinal Surgery.

Precise tumor localization during gastrointestinal surgery improves curability and function preservation. We investigated the efficacy of preoperative endoscopic fluorescent clip marking using a Zeoclip FS with built-in near-infrared fluorescent resins in delineating gastrointestinal cancer for surgery. We evaluated the intraoperative visibility of the Zeoclip FS using a VISERA ELITE 2 and the short-term outcomes of 37 cancer patients (colorectal, n=23; gastric, n=14) who underwent preoperative fluorescent clip marking. The study included 23 male and 14 female subjects with a mean age of 73 years (range=39-87 years). Thirty-three patients (89.1%) exhibited clear fluorescent clip marking and easily determined transection lines. Fluorescence was not observed in 1 sigmoid colon cancer patient (2.7%), who required a colonic stent for preoperative obstruction. Three patients (8.1%) required additional procedures for fluorescence visualization. Endoscopic fluorescent clip marking can delineate tumors well for determining the extent of resection.

An Invited Commentary on “Effectiveness and safety of tumor site marking with near-infrared fluorescent clips in colorectal laparoscopic surgery: A case series study”

An Invited Commentary on “Effectiveness and safety of tumor site marking with near-infrared fluorescent clips in colorectal laparoscopic surgery: A case series study”

A novel endoscopic fluorescent band ligation method for tumor localization.

Accurate tumor localization is essential for minimally invasive surgery. This study describes the development of a novel endoscopic fluorescent band ligation method for the rapid and accurate identification of tumor sites during surgery. The method utilized a fluorescent rubber band, made of indocyanine green (ICG) and a liquid rubber solution mixture, as well as a near-infrared fluorescence laparoscopic system with a dual light source using a high-powered light-emitting diode (LED) and a 785-nm laser diode. The fluorescent rubber bands were endoscopically placed on the mucosae of porcine stomachs and colons. During subsequent conventional laparoscopic stomach and colon surgery, the fluorescent bands were assayed using the near-infrared fluorescence laparoscopy system. The locations of the fluorescent clips were clearly identified on the fluorescence images in real time. The system was able to distinguish the two or three bands marked on the mucosal surfaces of the stomach and colon. Resection margins around the fluorescent bands were sufficient in the resected specimens obtained during stomach and colon surgery. These novel endoscopic fluorescent bands could be rapidly and accurately localized during stomach and colon surgery. Use of these bands may make possible the excision of exact target sites during minimally invasive gastrointestinal surgery.

Proximity-Induced Covalent Labeling of Proteins with a Reactive Fluorophore-Binding Peptide Tag.

Labeling of proteins with fluorescent dyes in live cells enables the investigation of their roles in biological systems by fluorescence microscopy. Because the labeling procedure should not disturb the native function of the protein of interest, it is of high importance to find the optimum labeling method for the problem to be studied. Here, we developed a rapid one-step method to covalently and site-specifically label proteins with a TexasRed fluorophore in vitro and in live bacteria. To this end, a genetically encodable TexasRed fluorophore-binding peptide (TR512) was converted into a reactive tag (ReacTR) by adjoining a cysteine residue which rapidly reacts with N-α-chloroacetamide-conjugated TexasRed fluorophore owing to the proximity effect; ReacTR tag first binds to the TexasRed fluorophore and this interaction brings the nucleophilic cysteine and the electrophilic N-α-chloroacetamide groups in close proximity. Our method has several advantages over existing methods: (i) it utilizes a peptide tag much smaller than fluorescent proteins, the SNAP, CLIP, or HaLo tags; (ii) it allows for labeling of proteins with a small, photostable, red-emitting TexasRed fluorophore; (iii) the probe used is very easy to synthesize; (iv) no enzyme is required to transfer the fluorophore to the peptide tag; and (v) labeling yields a stable covalent product in a very fast reaction.

Development of a new detection device using a glass clip emitting infrared fluorescence for laparoscopic surgery of gastric cancer

In conventional method, to identify location of the tumor intraperitoneally for extirpation of the gastric cancer, charcoal ink is injected around the primary tumor. However, in the time of laparoscopic operation, it is difficult to estimate specific site of primary tumor. In this study we developed a glass phosphors was realized with Yb3+, Nd3+ doped to Bi2O3-B2O3 based glasses, which have central emission wavelength of 1020 nm and 100 nm of FWHM. Using this glass phosphor, we developed a fluorescent clip and the laparoscopic fluorescent detection system for clip-derived near-infrared light. To evaluated clinical performance of a fluorescent clip and the laparoscopic detection system, we used resected stomach from the patients. Fluorescent clip was fixed on the gastric mucosa, and an excitation light (wavelength: 808nm) was irradiated from outside of stomach for detection of fluorescent through stomach wall. As a result, fluorescent emission from the clip was successfully detected. These results indicate that the glass fluorescent clip in combination with laparoscopic detection system is a very useful method to identify the exact location of the primary gastric cancer.

A novel endoscopic fluorescent clip visible with near-infrared imaging during laparoscopic surgery in a porcine model

In gastrointestinal cancer surgery, particularly in early cancer, accurate tumor localization is important in order to determine the extent of resection. In laparoscopic surgery, because of the inability to palpate the lesion, the most prevalent method of localization is endoscopic tattooing. However, complicated maneuvering makes it difficult to control local dye spreading and dye leakage into the intraperitoneal cavity. A simpler, safe method is needed. In this study, we developed a novel method for applying fluorescence-coated endoscopic clips to visualize locations inside the colon during laparoscopic surgery. We tested the procedure in an in vivo porcine model and with ex vivo human colon tissues. Bovine serum albumin was conjugated to indocyanine green or the succinimidyl ester CF™ 790 to form a pasty mixture, which was used to coat the front ends of endoscopic clips. The fluorescence-coated clips were endoscopically placed on the mucosal surface of a porcine colon. Using an Olympus near-infrared laparoscopy system, we attempted to identify the fluorescent clips from the outer, serosal side of the porcine colon during laparoscopic surgery in vivo. The clips were also evaluated using ex vivo human colon tissues. After placing two clips on the inner, mucosal surface of the porcine colon, we used near-infrared laparoscopy to view them from the outer, serosal surface of the colon in real time during in vivo laparoscopic surgery. We also identified the fluorescence-coated clips through human colon tissues in an ex vivo study. We developed a novel, fluorescence-coated clip that can be placed endoscopically for rapid, exact localization of colonic lesions. The clips were successfully visualized with near-infrared fluorescence imaging during laparoscopic surgery in an in vivo porcine model and in ex vivo human colon tissues.

Synthesis, Crystal Structure and Binding Properties of a New Fluorescent Molecular Clip Based on 2,5-diphenylfuran

A new fluorescent molecular clip derived from 2,5-diphenyl-furan with two benzo[d]-thiazole-2-thio-units as side walls has been synthesised and its structure and conformation confirmed by an X-ray structure. Fluorescence spectroscopic studies show that it can selectively bind Fe3+.

A novel endoscopic fluorescent clip for the localization of gastrointestinal tumors

Accurate tumor localization is essential for gastrointestinal surgery, especially in cases of early cancer. This study was designed to develop a novel fluorescent clip for rapid and exact visualization of tumor sites. A transparent polymer matrix containing highly bright fluorochromes was coated on the front end of endoscopic clips. The fluorescent clips were placed on the mucosal surface of a porcine colon and stomach, and the operator then attempted to identify the fluorescent clips from the outer serosal side of the colon and stomach. A 532-nm diode laser and filter glass were used for visualizing the fluorescence signals through the colonic tissue. A 650-nm diode laser and a digital charge-coupled device (CCD) camera equipped with a bandpass emission filter were used for the imaging of the fluorescent clips through the thick stomach tissue. When a green light from a 532-nm diode laser (power density=0.35 mW/cm2) was applied on the serosal surface of the porcine colon, we could identify all clips that had been placed endoscopically on the mucosal surface of the inner colonic wall. By using the light from a 650-nm diode laser (power density=0.7 mW/cm2), we identified all fluorescent clips through the stomach wall in real time. Similar results were also obtained with the filtered xenon lamp. An endoscopic fluorescent clip can be useful for the rapid and exact localization of tumors, and this technique can also be useful during laparoscopic surgery.

Synthesis and Binding Properties of a New Fluorescent Molecular Clip Based on 2-ethyl Cyanoacrylate

A new fluorescent molecular clip based on 2-ethyl cyanoacrylate has been synthesised and its binding properties investigated by fluorescence spectroscopy to show that it can selectively bind Fe3+ with fluorescence quenching.