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

doi:10.21203/rs.3.rs-3950561/v1

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

https://doi.org/10.21203/rs.3.rs-3950561/v1

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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

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.

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.

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/m² (range, 16.7–31.2 kg/m²). 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)

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.

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.

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No competing interests reported.

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

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