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

Fluorescence-guidance using near-infrared fluorescent clips in robotic rectal surgery: a case series | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Fluorescence-guidance using near-infrared fluorescent clips in robotic rectal surgery: a case series Satoshi Narihiro, Syunsuke Nakashima, Mutsumi Kazi, Tomotaka Kumamoto, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-3950561/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Tattoo markings are often used as preoperative markers for colorectal cancer. However, scattered ink markings adversely affects 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. Twenty consecutive patients who underwent robotic surgery for rectal cancer between December 2022 and December 2023 were enrolled in the study. The primary endpoints of this study 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. Clip locations were confirmed in 17 of 20 (85%) cases. There were seven (35%) cases with preoperative CRT and, of these, the detection of NIRFC was affected in 3 cases. No adverse events, including bleeding or perforation, were observed at the time of clipping, and no clippings were lost. The median DRM was 55 mm (range, 22–86 mm) for Rs, 33 mm (range, 16–60 mm) for Ra, and 20 mm (range, 17–30 mm) for Rb. The median number of lymph nodes was 13 (range, 10–21 mm). The rate of intraoperative clip detection, oncological assessment, including DRM, and the number of lymph nodes indicate that fluorescence-guided methods using NIRFCs are feasible for rectal cancer. Rectal cancer fluorescence-guided methods robotic surgery near-infrared fluorescent clips Figures Figure 1 Figure 2 Figure 3 Introduction Surgical curability and preservation of anal function are the main objectives in rectal cancer surgery. Regarding the curability rate of the intervention, rectal cancer has a higher rate of local recurrence than colon cancer [ 1 , 2 ]; hence, it is important to improve surgical quality. Distal resection margin (DRM) and total mesorectal excision (TME) have been proposed as curability evaluation methods for rectal cancer. An ideal DRM length is essential to eliminate lymph node metastasis in the mesentery [ 3 , 4 ], and TME surgery is the standard treatment for patients with lower rectal cancer [ 5 ]. Regarding anal function, low rectal cancer located near the anorectal junction was previously treated with abdominoperineal resection (APR); however, anal preservation was not achieved. However, improvements in surgery, including intersphincteric resection (ISR), have enabled additional anus-preserving surgical procedures. However, there are various factors that contribute to the degree of difficulty in surgery, such as narrow pelvis, obesity, and cases after preoperative therapy. In addition, there is no consensus on preoperative marking methods to be used for rectal cancer. Tattoo markings are often used as preoperative markers for colorectal cancer. However, the scattering of ink adversely affects recognition of the tumor site, which may lead to inaccurate DRM and incomplete TME in patients with rectal cancer [ 6 , 7 ]. Preoperative chemoradiation therapy (CRT) is a standard treatment option for patients with rectal cancer [ 5 , 8 , 9 ]. These modalities reduce the size of primary lesions. Consequently, the intestinal resection length was shortened and anal function was preserved. In such cases, tattooing is considered unsuitable as a marking method. For these reasons, we used the near-infrared fluorescence clips (NIRFCs) (ZEOCLIP FS®) (Zeon Medical, Tokyo, Japan) as a preoperative marking method [ 7 ]. Robotic surgery for rectal cancer is becoming increasingly popular. The Da Vinci® Xi surgical system is an integrated fluorescence imaging (firefly technology) system. The endoscope camera contains an infrared excitation laser (805 nm) that visualizes infrared light (830 nm) [ 10 – 12 ], and firefly technology enables fluorescence-guided surgery using NIRFC [ 7 ]. This study presents the first case series of fluorescence-guided robotic rectal surgery that utilized firefly technology, and NIRFCs was used to localize rectal cancer lesions. This study evaluated the feasibility and safety of fluorescence-guided robotic rectal surgeries. Materials and Methods Twenty consecutive patients who underwent robotic surgery for rectal cancer between December 2022 and December 2023 were enrolled. The study obtained approval from the Institutional Review Board [No. 30–249(9270)] prior to patient enrolment. Written informed consent was obtained from all patients for participation in the study. The authors affirm that human research participants provided informed consent for publication of the images in Figure(s) 1, 2 and 3.” All patients were treated and followed up at the same medical academic institution. This was a prospective, single-center study. For all patients, clip placement was performed by the same endoscopist (SA), and robotic surgery was performed by two surgeons (SN and KK), senior colon and rectal surgery specialists, respectively. For all patients, the NIRFC was placed during colonoscopy performed 1 day before surgery. All patients underwent bowel preparation before colonoscopy. In each case, four clips were attached to the intestinal mucosa intraluminally, close to the distal extent of the lesion, four clips for each lesion, each clip at 90° distance from the others. This method of clip detection is the same as that used in our previous report [ 6 , 7 ]. The primary endpoints of this study were the rate of intraoperative clip detection and its usefulness for pre-operative marking of the tumor site. The secondary endpoints were oncological assessments, including DRM and the number of lymph nodes. Results All the enrolled 20 patients underwent robotic rectal surgery. There were 14 men and 6 women, with a median age of 70 years (range, 49–83 years). Their median BMI was 23.5 kg/m 2 (range, 16.7–31.2 kg/m 2 ). The tumors were located at the Rs (n = 9), Ra (n = 7), and Rb (n = 4) level (Fig. 1 ). With regard to cancer progression, five patients had stage I tumors, six patients had stage II tumors, six patients had stage III tumors, three patients had stage IV tumors, and seven (35%) patients underwent preoperative CRT (Table 1 ). Table 1 Patient and surgical characteristics N = 20 Sex (M:F) 14:6 Median age (range), years 70 (49–83) BMI (range) 23.5(16.7–31.2) Comorbidity 7 (35%) Open surgery history 3 (15%) Tumor lesion (Rs: Ra :Rb) 9 (45%) :7 (35%) :4 (20%) Clinical stage ( Ⅰ: Ⅱ: Ⅲ: Ⅳ) 5 (25%) :6 (30%) :6 (30%): 3 (15%) T4 1 Preoperative CRT 7 (35%) Thick fatty tissue deposits 1 Tumor size (mm) 34 (11–95) Type of operation HAR LAR Hartoman 8 (40%) 11 (55%) 1 (5%) Numbers reported as median (range) or n (%) BMI, body mass index; CRT, chemoradiotherapy; HAR, high anterior resection; LAR, low anterior resection. Preoperative colonoscopy was performed on the day preceding the surgery in all patients. Clip locations were confirmed using firefly technology in 17 of 20 (85%) patients. The clip location of the Rs area was confirmed in nine cases (100%). The Ra area was confirmed in 4 cases (100%), and the Ra area with preoperative CRT was confirmed in 1 case (33%). The Rb area was confirmed in 1 case (100%) and the Rb area with preoperative CRT was confirmed in 2 cases (67%). There was one patient with T4 tumor progression and one patient with thick fatty tissue deposits around the colon; in such patients, these potentially interfering issues did not affect the detection of NIRFC. However, there were 7 (35%) cases with preoperative CRT and, of these, for 3 cases the detection of the NIRFC was affected (Table 2 ). We did not observe any cases in which the clips were dislodged or caught in the linear stapler at the time of intestinal dissection. No adverse events, including bleeding or perforation, were observed at the time of clip insertion, and no clips slipped off. The median DRM was 55 mm (range, 22–86 mm) for Rs, 33 mm (range, 16–60 mm) for Ra, and 20 mm (range, 17–30 mm) for Rb. The median number of lymph nodes was 13 (range, 10–21 mm) (Table 3 ). Table 2 Clip recognition rate N = 20 Positive Negative Total Rs Ra Ra་Preoperative CRT Rb Rb་Preoperative CRT 17 (85%) 9 (100%) 4 (100%) 1 (33%) 1 (100%) 2 (67%) 3 (15%) 0 0 2 (67%) 0 1 (33%) Numbers reported as n (%) CRT, chemoradiotherapy Table 3 Peri-operative and postoperative outcomes Outcome (N = 20) Operation time (min) 378.5 (257–612) Blood loss (mL) 55 (5–200) Intraoperative complications 0 Reoperation 0 Mortality 0 Distal resection margin (mm) Rs Ra Rb 55 (22–86) 33 (16–60) 20 (17–30) Number of harvested LLNs 13 (10–21) Length of postoperative hospital stay (days) 14.5 (9–68) Numbers reported as median (range) Discussion In this study, we demonstrated that clip locations could be confirmed using firefly technology in 17 of 20 (85%) cases. In addition, there were no adverse events due to clip attachment or due to clips dropping out. In the oncological assessment, the ideal length of the DRM was sufficient and the number of lymph nodes removed during dissection was correct. These results indicate that fluorescence-guided methods using NIRFCs are safe and feasible for the treatment of rectal cancer. The tattoo marking used for preoperative marking has various disadvantages, such as unclear range, excessively thin marking, and scattered ink. In rectal cancer, a shorter DRM and an unsuitable TME increase the risk of local recurrence and decrease the overall survival rate [ 3 – 5 ]. An unclear range or excessively thin markings make it difficult to recognize the optimal DRM. The scattered ink makes it difficult to identify the optimal DRM and TME layers. Therefore, it is not suitable for the treatment of rectal cancer. To achieve a complete TME and optimal DRM, tumor site marking with NIRFCs may be used as an alternative to tattoo marking, which results in various problems such as unclear range, excessively thin marking, and scattered ink. The advantage of using NIFRCs as a preoperative marking method is that tumors can be extracted more precisely [ 6 , 7 , 13 ]. Therefore, we attempted to apply NIFRCs as a marking method for rectal cancer. This has oncological benefits in rectal cancer; it involves selection of the optimal intestinal incision length (optimal DRM) and correct dissection surface (correct TME layer). To demonstrate the benefits of NIFRCs in rectal cancer, it is important to carefully evaluate their visibility. One patient with T4 tumor progression and one patient with thick fatty tissue deposits around the rectum presented potentially interfering issues but these did not affect the detection of NIFRCs. Despite an almost complete retention rate among all patients, the tumor locations could not be identified in three cases, and preoperative CRT was performed for all three cases. CRT is known to induce inflammation, necrosis, and fibrosis, resulting in thickening of the rectal wall [ 14 , 15 ] (Fig. 2 ). For the CRT, it was necessary to obtain the strongest near-infrared signal. Three approaches have been used. The first is to compress the intestinal tract to minimize soft tissue penetration. In the second, the laparoscope is positioned vertically to obtain a sufficient angle of fluorescence excitation to detect the clip. The intestine must be mobilized before proper positioning of the laparoscope. Third, we considered a new clip-attachment method. This made it easier to obtain near-infrared signals by concentrating the clip only on the ventral side rather than hitting the entire circumference (Fig. 3 ). This study had several limitations. First, owing to the small sample size and retrospective, single-center, non-randomized design, potential bias could not be eliminated. Second, all operative procedures were performed by two surgeons and endoscopists; such a setting might have been a possible source of optimism bias. Third, we could not evaluate circumferential RM (CRM) for oncological assessment. Similar to DRM and TME, CRM influences the local recurrence rate. After preoperative treatment, the 5-year local recurrence rate for a CRM measuring > 1 mm was significantly lower than those ≤ 1 mm [ 16 , 17 ]; hence, we should evaluate CRM as an oncological endpoint in the future. Fourth, NIFRCs are expensive (the required cost is approximately $ 100 per 1 fluorescent clip); therefore, we need to reduce the number of clip placements as much as possible. However, there are advantages, such as optimal intestinal incision length (optimal DRM) and correct dissection surface (correct TME layer). Accordingly, it is important to analyze the oncological outcomes and total costs of both procedures. In conclusion, the fluorescence-guided method using NIRFCs was safe and feasible for rectal cancer; hence, we believe that this method using NIRFCs can be a promising surgical option in rectal cancer resection. Declarations Statements and Declarations Funding The authors declare that no funds, grants, or other support were received during the preparation of this manuscript. Competing interests The authors have no conflicts of interest or financial ties to disclose. Author contributions SN made substantial contributions to the study conception and design, data acquisition, and the analysis and interpretation of the collected data. SN, MK, TK, KK, and NT were involved in discussions regarding this study. KE gave the final approval of the manuscript to be published. All authors have read and approved the final manuscript. Ethical considerations The study obtained approval from the Institutional Review Board [No. 30-249(9270)] prior to patient enrolment. Informed consent was obtained from all individual participants included in the study. References Harris GJ, Church JM, Senagore AJ et al (2002) Factors affecting local recurrence of colonic adenocarcinoma. Dis Colon Rectum 45:1029–1034. https://doi.org/10.1007/s10350-004-6355-1 Hashiguchi Y, Muro K, Saito Y et al (2020) Japanese Society for Cancer of the Colon and Rectum (JSCCR) guidelines 2019 for the treatment of colorectal cancer. Int J Clin Oncol 25:1–42. https://doi.org/10.1007/s10147-019-01485-z Park IJ, Kim JC (2010) Adequate length of the distal resection margin in rectal cancer: from the oncological point of view. J Gastrointest Surg 14:1331–1337. https://doi.org/10.1007/s11605-010-1165-3 Hohenberger W, Weber K, Matzel K, Papadopoulos T, Merkel S (2009) Standardized surgery for colonic cancer: complete mesocolic excision and central ligation – technical notes and outcome. Colorectal Dis 11:354–64; discussion 364. https://doi.org/10.1111/j.1463-1318.2008.01735.x Kennecke HF, Bahnson HT, Lin B et al (2022) Patterns of practice and improvements in survival among patients with stage 2/3 rectal cancer treated with trimodality therapy. JAMA Oncol 8:1466–1470. https://doi.org/10.1001/jamaoncol.2022.2831 Narihiro S, Yoshida M, Ohdaira H et al (2020) Effectiveness and safety of tumor site marking with near-infrared fluorescent clips in colorectal laparoscopic surgery: A case series study. Int J Surg 80:74–78. https://doi.org/10.1016/j.ijsu.2020.06.014 Narihiro S, Nakashima S, Kazi M, Yoshioka S, Kitagawa K, Toya N, Eto K (2023) Effectiveness of fluorescence-guided methods using near-infrared fluorescent clips of robotic colorectal surgery: a case report. Surg Case Rep 17:9(1):81. https://doi.org/10.1186/s40792-023-01666-z Sauer R, Becker H, Hohenberger W et al (2004) Preoperative versus postoperative chemoradiotherapy for rectal cancer. N Engl J Med 351:1731–1740. https://doi.org/10.1056/NEJMoa040694 Sebag-Montefiore D, Stephens RJ, Steele R et al (2009) Preoperative radiotherapy versus selective postoperative chemoradiotherapy in patients with rectal cancer (MRC CR07 and NCIC-CTG C016): a multicentre, randomised trial. Lancet 373:811–820. https://doi.org/10.1016/S0140-6736(09)60484-0 Lue JR, Pyrzak A, Allen J (2016) Improving accuracy of intraoperative diagnosis of endometriosis: role of firefly in minimal access robotic surgery. J Minim Access Surg 12:186–189. https://doi.org/10.4103/0972-9941.158969 Lee YJ, van den Berg NS, Orosco RK, Rosenthal EL, Sorger JM (2021) A narrative review of fluorescence imaging in robotic-assisted surgery. Laparosc Surg 5:31. https://doi.org/10.21037/ls-20-98 Ghuman A, Kavalukas S, Sharp SP, Wexner SD (2020) Clinical role of fluorescence imaging in colorectal surgery – an updated review. Expert Rev Med Devices 17:1277–1283. https://doi.org/10.1080/17434440.2020.1851191 Messenger DE (2020) Commentary: effectiveness and safety of tumor site marking with near-infrared fluorescent clips in colorectal laparoscopic surgery: A case series study. Int J Surg 81:84. https://doi.org/10.1016/j.ijsu.2020.07.048 Du C, Xue W, Li J, Cai Y, Gu J (2012) Morphology and prognostic value of tumor budding in rectal cancer after neoadjuvant radiotherapy. Hum Pathol 43:1061–1067. https://doi.org/10.1016/j.humpath.2011.07.026 Lee CT, Chow NH, Liu YS et al (2012) Computed tomography with histological correlation for evaluating tumor regression of rectal carcinoma after preoperative chemoradiation therapy. Hepato-Gastroenterology 59:2484–2489. https://doi.org/10.5754/hge12165 Nardi PD, Carvello M (2013) How reliable is current imaging in restaging rectal cancer after neoadjuvant therapy? World J Gastroenterol 19:5964–5972. https://doi.org/10.3748/wjg.v19.i36.5964 [PMID: 24106396 DOI: 10.3748/wjg.v19.i36.5964] Trakarnsanga A, Gonen M, Shia J et al (2013) What is the significance of the circumferential margin in locally advanced rectal cancer after neoadjuvant chemoradiotherapy? Ann Surg Oncol 20:1179–1184. https://doi.org/10.1245/s10434-012-2722-7 Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-3950561","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":272576083,"identity":"c7b1dbb5-3aab-48a5-a436-d2f3b347ed95","order_by":0,"name":"Satoshi Narihiro","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA5UlEQVRIiWNgGAWjYLCChB//6vkZGNjgfMJaHvYcSJBsIEUL4wO2AwkGBxBa8ANz9uMPPyTw3MkzvpH87MGHCgZ5oAufPcCnxbInx1giweJZsdmNNHPDGWcYDGc2MKQb4NNicCCHQSKBh5lx240EM2neNgaQC9Mk8Go5//zxjwQ2ZsbNM9K/EakFaLhEAtvhxA0SOcTacuONmUViT5qxxJk3ZZIzzkgYzmwm5Jfz6Y9v/vhhI8ffnr5N4kOFjTw/e0/aA3xaEEAgAUQCncTMk0acDgb+AzAW+zEitYyCUTAKRsEIAQB2ykuZte9GSAAAAABJRU5ErkJggg==","orcid":"","institution":"Department of Surgery, The Jikei University Kashiwa Hospital","correspondingAuthor":true,"prefix":"","firstName":"Satoshi","middleName":"","lastName":"Narihiro","suffix":""},{"id":272576084,"identity":"b8f3ee79-e77d-4a99-b934-277b6b07f815","order_by":1,"name":"Syunsuke Nakashima","email":"","orcid":"","institution":"Department of Surgery, The Jikei University Kashiwa Hospital","correspondingAuthor":false,"prefix":"","firstName":"Syunsuke","middleName":"","lastName":"Nakashima","suffix":""},{"id":272576085,"identity":"231f3a52-4ed8-4b88-88d5-e30cbb29b047","order_by":2,"name":"Mutsumi Kazi","email":"","orcid":"","institution":"Department of Surgery, The Jikei University Kashiwa Hospital","correspondingAuthor":false,"prefix":"","firstName":"Mutsumi","middleName":"","lastName":"Kazi","suffix":""},{"id":272576086,"identity":"f67c07c2-83d8-4036-a1c4-bc1f9260c4b3","order_by":3,"name":"Tomotaka Kumamoto","email":"","orcid":"","institution":"Department of Surgery, The Jikei University Kashiwa Hospital","correspondingAuthor":false,"prefix":"","firstName":"Tomotaka","middleName":"","lastName":"Kumamoto","suffix":""},{"id":272576087,"identity":"c642eecc-70e9-46a9-bd7a-8e8a94af229f","order_by":4,"name":"Kazuo Kitagawa","email":"","orcid":"","institution":"Department of Surgery, The Jikei University Kashiwa Hospital","correspondingAuthor":false,"prefix":"","firstName":"Kazuo","middleName":"","lastName":"Kitagawa","suffix":""},{"id":272576088,"identity":"dfd5b204-829e-4b26-bd43-f6eec9526105","order_by":5,"name":"Naoki Toya","email":"","orcid":"","institution":"Department of Surgery, The Jikei University Kashiwa Hospital","correspondingAuthor":false,"prefix":"","firstName":"Naoki","middleName":"","lastName":"Toya","suffix":""},{"id":272576089,"identity":"e28378fc-cc42-4ac2-acdd-9fcf041a2407","order_by":6,"name":"Ken Eto","email":"","orcid":"","institution":"Department of Surgery, The Jikei University School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Ken","middleName":"","lastName":"Eto","suffix":""}],"badges":[],"createdAt":"2024-02-12 08:44:57","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-3950561/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-3950561/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":51141744,"identity":"f73cb8e4-8561-4305-8060-ce8cf92a29d9","added_by":"auto","created_at":"2024-02-14 20:23:21","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":700608,"visible":true,"origin":"","legend":"\u003cp\u003eLocations of the Da Vinci-compatible NIRFCs were confirmed using firefly technology in each area of the rectal cancer\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-3950561/v1/cee50e526b656d7e1b46add0.png"},{"id":51142308,"identity":"bd7d0d90-5792-462d-9f14-272e6644d5e4","added_by":"auto","created_at":"2024-02-14 20:31:21","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":1019652,"visible":true,"origin":"","legend":"\u003cp\u003eRectal wall of preoperative CRT showed thickening; thus, the tumor lesion could not be identified\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-3950561/v1/a4d0a2d82fb01c3072f7ed33.png"},{"id":51141746,"identity":"3901f268-0287-4456-8e57-d7f8b2b1b6a0","added_by":"auto","created_at":"2024-02-14 20:23:21","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":1104311,"visible":true,"origin":"","legend":"\u003cp\u003eThe proposed new clip attachment method improves visualization of near-infrared signals by concentrating the clip only on the ventral side\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-3950561/v1/ce66eae116a4a96e94331583.png"},{"id":51142532,"identity":"dc891ccd-b670-42bc-b118-8b004252da72","added_by":"auto","created_at":"2024-02-14 20:47:23","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2624970,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-3950561/v1/895865de-816b-4668-8c7d-3c0711ba6276.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Fluorescence-guidance using near-infrared fluorescent clips in robotic rectal surgery: a case series","fulltext":[{"header":"Introduction","content":"\u003cp\u003eSurgical curability and preservation of anal function are the main objectives in rectal cancer surgery. Regarding the curability rate of the intervention, rectal cancer has a higher rate of local recurrence than colon cancer [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]; hence, it is important to improve surgical quality. Distal resection margin (DRM) and total mesorectal excision (TME) have been proposed as curability evaluation methods for rectal cancer. An ideal DRM length is essential to eliminate lymph node metastasis in the mesentery [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e], and TME surgery is the standard treatment for patients with lower rectal cancer [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Regarding anal function, low rectal cancer located near the anorectal junction was previously treated with abdominoperineal resection (APR); however, anal preservation was not achieved. However, improvements in surgery, including intersphincteric resection (ISR), have enabled additional anus-preserving surgical procedures. However, there are various factors that contribute to the degree of difficulty in surgery, such as narrow pelvis, obesity, and cases after preoperative therapy. In addition, there is no consensus on preoperative marking methods to be used for rectal cancer.\u003c/p\u003e \u003cp\u003eTattoo markings are often used as preoperative markers for colorectal cancer. However, the scattering of ink adversely affects recognition of the tumor site, which may lead to inaccurate DRM and incomplete TME in patients with rectal cancer [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Preoperative chemoradiation therapy (CRT) is a standard treatment option for patients with rectal cancer [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. These modalities reduce the size of primary lesions. Consequently, the intestinal resection length was shortened and anal function was preserved. In such cases, tattooing is considered unsuitable as a marking method. For these reasons, we used the near-infrared fluorescence clips (NIRFCs) (ZEOCLIP FS\u0026reg;) (Zeon Medical, Tokyo, Japan) as a preoperative marking method [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eRobotic surgery for rectal cancer is becoming increasingly popular. The Da Vinci\u0026reg; Xi surgical system is an integrated fluorescence imaging (firefly technology) system. The endoscope camera contains an infrared excitation laser (805 nm) that visualizes infrared light (830 nm) [\u003cspan additionalcitationids=\"CR11\" citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e], and firefly technology enables fluorescence-guided surgery using NIRFC [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThis study presents the first case series of fluorescence-guided robotic rectal surgery that utilized firefly technology, and NIRFCs was used to localize rectal cancer lesions. This study evaluated the feasibility and safety of fluorescence-guided robotic rectal surgeries.\u003c/p\u003e"},{"header":"Materials and Methods","content":"\u003cp\u003eTwenty consecutive patients who underwent robotic surgery for rectal cancer between December 2022 and December 2023 were enrolled. The study obtained approval from the Institutional Review Board [No. 30\u0026ndash;249(9270)] prior to patient enrolment. Written informed consent was obtained from all patients for participation in the study. The authors affirm that human research participants provided informed consent for publication of the images in Figure(s) 1, 2 and 3.\u0026rdquo; All patients were treated and followed up at the same medical academic institution. This was a prospective, single-center study. For all patients, clip placement was performed by the same endoscopist (SA), and robotic surgery was performed by two surgeons (SN and KK), senior colon and rectal surgery specialists, respectively.\u003c/p\u003e \u003cp\u003eFor all patients, the NIRFC was placed during colonoscopy performed 1 day before surgery. All patients underwent bowel preparation before colonoscopy. In each case, four clips were attached to the intestinal mucosa intraluminally, close to the distal extent of the lesion, four clips for each lesion, each clip at 90\u0026deg; distance from the others. This method of clip detection is the same as that used in our previous report [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe primary endpoints of this study were the rate of intraoperative clip detection and its usefulness for pre-operative marking of the tumor site. The secondary endpoints were oncological assessments, including DRM and the number of lymph nodes.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eAll the enrolled 20 patients underwent robotic rectal surgery. There were 14 men and 6 women, with a median age of 70 years (range, 49\u0026ndash;83 years). Their median BMI was 23.5 kg/m\u003csup\u003e2\u003c/sup\u003e (range, 16.7\u0026ndash;31.2 kg/m\u003csup\u003e2\u003c/sup\u003e). The tumors were located at the Rs (n\u0026thinsp;=\u0026thinsp;9), Ra (n\u0026thinsp;=\u0026thinsp;7), and Rb (n\u0026thinsp;=\u0026thinsp;4) level (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). With regard to cancer progression, five patients had stage I tumors, six patients had stage II tumors, six patients had stage III tumors, three patients had stage IV tumors, and seven (35%) patients underwent preoperative CRT (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003ePatient and surgical characteristics\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eN\u0026thinsp;=\u0026thinsp;20\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSex (M:F)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e14:6\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMedian age (range), years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e70 (49\u0026ndash;83)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBMI (range)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e23.5(16.7\u0026ndash;31.2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eComorbidity\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7 (35%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOpen surgery history\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 (15%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTumor lesion (Rs: Ra :Rb)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9 (45%) :7 (35%) :4 (20%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eClinical stage ( Ⅰ: Ⅱ: Ⅲ: Ⅳ)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5 (25%) :6 (30%) :6 (30%): 3 (15%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eT4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePreoperative CRT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7 (35%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eThick fatty tissue deposits\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTumor size (mm)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e34 (11\u0026ndash;95)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eType of operation\u003c/p\u003e \u003cp\u003eHAR\u003c/p\u003e \u003cp\u003eLAR\u003c/p\u003e \u003cp\u003eHartoman\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8 (40%)\u003c/p\u003e \u003cp\u003e11 (55%)\u003c/p\u003e \u003cp\u003e1 (5%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"2\"\u003eNumbers reported as median (range) or n (%)\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"2\"\u003eBMI, body mass index; CRT, chemoradiotherapy; HAR, high anterior resection; LAR, low anterior resection.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003ePreoperative colonoscopy was performed on the day preceding the surgery in all patients. Clip locations were confirmed using firefly technology in 17 of 20 (85%) patients. The clip location of the Rs area was confirmed in nine cases (100%). The Ra area was confirmed in 4 cases (100%), and the Ra area with preoperative CRT was confirmed in 1 case (33%). The Rb area was confirmed in 1 case (100%) and the Rb area with preoperative CRT was confirmed in 2 cases (67%). There was one patient with T4 tumor progression and one patient with thick fatty tissue deposits around the colon; in such patients, these potentially interfering issues did not affect the detection of NIRFC. However, there were 7 (35%) cases with preoperative CRT and, of these, for 3 cases the detection of the NIRFC was affected (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). We did not observe any cases in which the clips were dislodged or caught in the linear stapler at the time of intestinal dissection. No adverse events, including bleeding or perforation, were observed at the time of clip insertion, and no clips slipped off. The median DRM was 55 mm (range, 22\u0026ndash;86 mm) for Rs, 33 mm (range, 16\u0026ndash;60 mm) for Ra, and 20 mm (range, 17\u0026ndash;30 mm) for Rb. The median number of lymph nodes was 13 (range, 10\u0026ndash;21 mm) (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eClip recognition rate\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eN\u0026thinsp;=\u0026thinsp;20\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePositive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNegative\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTotal\u003c/p\u003e \u003cp\u003eRs\u003c/p\u003e \u003cp\u003eRa\u003c/p\u003e \u003cp\u003eRa་Preoperative CRT\u003c/p\u003e \u003cp\u003eRb\u003c/p\u003e \u003cp\u003eRb་Preoperative CRT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e17 (85%)\u003c/p\u003e \u003cp\u003e9 (100%)\u003c/p\u003e \u003cp\u003e4 (100%)\u003c/p\u003e \u003cp\u003e1 (33%)\u003c/p\u003e \u003cp\u003e1 (100%)\u003c/p\u003e \u003cp\u003e2 (67%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (15%)\u003c/p\u003e \u003cp\u003e0\u003c/p\u003e \u003cp\u003e0\u003c/p\u003e \u003cp\u003e2 (67%)\u003c/p\u003e \u003cp\u003e0\u003c/p\u003e \u003cp\u003e1 (33%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eNumbers reported as n (%)\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eCRT, chemoradiotherapy\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003ePeri-operative and postoperative outcomes\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOutcome\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003e(N\u0026thinsp;=\u0026thinsp;20)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOperation time (min)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e378.5 (257\u0026ndash;612)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBlood loss (mL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e55 (5\u0026ndash;200)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIntraoperative complications\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eReoperation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMortality\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDistal resection margin (mm)\u003c/p\u003e \u003cp\u003eRs\u003c/p\u003e \u003cp\u003eRa\u003c/p\u003e \u003cp\u003eRb\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e55\u0026nbsp;(22\u0026ndash;86)\u003c/p\u003e \u003cp\u003e33 (16\u0026ndash;60)\u003c/p\u003e \u003cp\u003e20 (17\u0026ndash;30)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNumber of harvested LLNs\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e13 (10\u0026ndash;21)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLength of postoperative hospital stay (days)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e14.5 (9\u0026ndash;68)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"2\"\u003eNumbers reported as median (range)\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn this study, we demonstrated that clip locations could be confirmed using firefly technology in 17 of 20 (85%) cases. In addition, there were no adverse events due to clip attachment or due to clips dropping out. In the oncological assessment, the ideal length of the DRM was sufficient and the number of lymph nodes removed during dissection was correct. These results indicate that fluorescence-guided methods using NIRFCs are safe and feasible for the treatment of rectal cancer.\u003c/p\u003e \u003cp\u003eThe tattoo marking used for preoperative marking has various disadvantages, such as unclear range, excessively thin marking, and scattered ink. In rectal cancer, a shorter DRM and an unsuitable TME increase the risk of local recurrence and decrease the overall survival rate [\u003cspan additionalcitationids=\"CR4\" citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. An unclear range or excessively thin markings make it difficult to recognize the optimal DRM. The scattered ink makes it difficult to identify the optimal DRM and TME layers. Therefore, it is not suitable for the treatment of rectal cancer. To achieve a complete TME and optimal DRM, tumor site marking with NIRFCs may be used as an alternative to tattoo marking, which results in various problems such as unclear range, excessively thin marking, and scattered ink.\u003c/p\u003e \u003cp\u003eThe advantage of using NIFRCs as a preoperative marking method is that tumors can be extracted more precisely [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Therefore, we attempted to apply NIFRCs as a marking method for rectal cancer. This has oncological benefits in rectal cancer; it involves selection of the optimal intestinal incision length (optimal DRM) and correct dissection surface (correct TME layer). To demonstrate the benefits of NIFRCs in rectal cancer, it is important to carefully evaluate their visibility. One patient with T4 tumor progression and one patient with thick fatty tissue deposits around the rectum presented potentially interfering issues but these did not affect the detection of NIFRCs.\u003c/p\u003e \u003cp\u003eDespite an almost complete retention rate among all patients, the tumor locations could not be identified in three cases, and preoperative CRT was performed for all three cases. CRT is known to induce inflammation, necrosis, and fibrosis, resulting in thickening of the rectal wall [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e] (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). For the CRT, it was necessary to obtain the strongest near-infrared signal. Three approaches have been used. The first is to compress the intestinal tract to minimize soft tissue penetration. In the second, the laparoscope is positioned vertically to obtain a sufficient angle of fluorescence excitation to detect the clip. The intestine must be mobilized before proper positioning of the laparoscope. Third, we considered a new clip-attachment method. This made it easier to obtain near-infrared signals by concentrating the clip only on the ventral side rather than hitting the entire circumference (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e This study had several limitations. First, owing to the small sample size and retrospective, single-center, non-randomized design, potential bias could not be eliminated. Second, all operative procedures were performed by two surgeons and endoscopists; such a setting might have been a possible source of optimism bias. Third, we could not evaluate circumferential RM (CRM) for oncological assessment. Similar to DRM and TME, CRM influences the local recurrence rate. After preoperative treatment, the 5-year local recurrence rate for a CRM measuring\u0026thinsp;\u0026gt;\u0026thinsp;1 mm was significantly lower than those\u0026thinsp;\u0026le;\u0026thinsp;1 mm [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]; hence, we should evaluate CRM as an oncological endpoint in the future. Fourth, NIFRCs are expensive (the required cost is approximately \u003cspan\u003e$\u003c/span\u003e100 per 1 fluorescent clip); therefore, we need to reduce the number of clip placements as much as possible. However, there are advantages, such as optimal intestinal incision length (optimal DRM) and correct dissection surface (correct TME layer). Accordingly, it is important to analyze the oncological outcomes and total costs of both procedures.\u003c/p\u003e \u003cp\u003e In conclusion, the fluorescence-guided method using NIRFCs was safe and feasible for rectal cancer; hence, we believe that this method using NIRFCs can be a promising surgical option in rectal cancer resection.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eStatements and Declarations\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that no funds, grants, or other support were received during the preparation of this manuscript.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors have no conflicts of interest or financial ties to disclose.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSN made substantial contributions to the study conception and design, data acquisition, and the analysis and interpretation of the collected data. SN, MK, TK, KK, and NT were involved in discussions regarding this study. KE gave the final approval of the manuscript to be published. All authors have read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthical considerations\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study obtained approval from the Institutional Review Board [No. 30-249(9270)] prior to patient enrolment. Informed consent was obtained from all individual participants included in the study.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eHarris GJ, Church JM, Senagore AJ et al (2002) Factors affecting local recurrence of colonic adenocarcinoma. 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Ann Surg Oncol 20:1179\u0026ndash;1184. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1245/s10434-012-2722-7\u003c/span\u003e\u003cspan address=\"10.1245/s10434-012-2722-7\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Rectal cancer, fluorescence-guided methods, robotic surgery, near-infrared fluorescent clips","lastPublishedDoi":"10.21203/rs.3.rs-3950561/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-3950561/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eTattoo markings are often used as preoperative markers for colorectal cancer. However, scattered ink markings adversely affects 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. Twenty consecutive patients who underwent robotic surgery for rectal cancer between December 2022 and December 2023 were enrolled in the study. The primary endpoints of this study 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. Clip locations were confirmed in 17 of 20 (85%) cases. There were seven (35%) cases with preoperative CRT and, of these, the detection of NIRFC was affected in 3 cases. No adverse events, including bleeding or perforation, were observed at the time of clipping, and no clippings were lost. The median DRM was 55 mm (range, 22\u0026ndash;86 mm) for Rs, 33 mm (range, 16\u0026ndash;60 mm) for Ra, and 20 mm (range, 17\u0026ndash;30 mm) for Rb. The median number of lymph nodes was 13 (range, 10\u0026ndash;21 mm). The rate of intraoperative clip detection, oncological assessment, including DRM, and the number of lymph nodes indicate that fluorescence-guided methods using NIRFCs are feasible for rectal cancer.\u003c/p\u003e","manuscriptTitle":"Fluorescence-guidance using near-infrared fluorescent clips in robotic rectal surgery: a case series","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-02-14 20:23:16","doi":"10.21203/rs.3.rs-3950561/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"98edd309-f6ff-4034-ab4f-336a5353e554","owner":[],"postedDate":"February 14th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-02-26T03:59:55+00:00","versionOfRecord":[],"versionCreatedAt":"2024-02-14 20:23:16","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-3950561","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-3950561","identity":"rs-3950561","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}