Red dichromatic imaging improved the visibility of exposed blood vessels in gastric ulcer induced by endoscopic submucosal dissection– a pilot study

doi:10.21203/rs.3.rs-1983199/v1

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Red dichromatic imaging improved the visibility of exposed blood vessels in gastric ulcer induced by endoscopic submucosal dissection– a pilot study

https://doi.org/10.21203/rs.3.rs-1983199/v1

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Background

One of the major complications of gastric endoscopic submucosal dissection (ESD) is delayed bleeding. The treatment of exposed vessels after completed dissection should be effective to avoid delayed bleeding. However, it’s sometimes difficult to detect the detection of exposed blood vessels on ulcers induced by ESD. A recent study reported that red dichromatic imaging (RDI) was useful for detecting exposed vessels. In this study, we aimed to measure the visibility of exposed vessels and the quantitative color difference between the exposed vessels and surrounding tissue on ulcers, as observed using RDI after completed dissection.

Methods

Sixty-four vessels (14 patients) in gastric ESD-induced ulcers were evaluated using both white light imaging (WLI) and RDI. The Commission Internationale de l’Eclairage 1976 (L*a*b*) color space was used to measure the color difference. The color difference was evaluated by comparing the color values of regions of interest for the point of an exposed vessel and three points surrounding an exposed vessel. The visibility of exposed vessels was evaluated using a visibility scoring system. The primary endpoint was color differences (ΔE) between the exposed vessels and surrounding tissue in each modality.

Results

The average ΔE values (± SEM) for WLI and RDI were 24.85 (± 1.19) and 31.83(± 1.31), respectively. The ΔE value for RDI was significantly higher than that for WLI (p < 0.01). The visibility score was improved in 54.7% (35/64) of cases.

Conclusions

The color differences between the exposed vessels and surrounding tissue on gastric ESD-induced ulcers were higher with RDI than with WLI, and RDI improved the visibility of exposed vessels.

Red dichromatic imaging

Endoscopic submucosal dissection

Delayed bleeding

Image-enhanced endoscopy

CIE1976 (L*a*b*) color space

visibility of exposed vessels

Endoscopic submucosal dissection (ESD) has been widely performed as a treatment for gastric tumors. However, some complications after gastric ESD have been reported[1], and the delayed bleeding is one of the major complications[2, 3]. Specifically, delayed bleeding tends to occur in patients treated with antithrombotic drugs[4]. Therefore, some methods have been reported to prevent delayed bleeding[5]: post-ESD coagulation; coagulation plus artery-selective clipping (2C)[6]; the search, coagulation, and clipping method[7]; and the combination of search, coagulation, clipping, and polyglycolic acid sheet method[8]. These methods are effective for preventing delayed bleeding, as they treat exposed blood vessels in ESD-induced ulcers. However, it is sometimes difficult to detect exposed blood vessels on ulcers induced by ESD.

Red dichromatic imaging (RDI; dual red imaging) is an image-enhanced endoscopy technology. It uses three wavelengths (540, 600, and 630 nm) (Olympus Medical Systems, Tokyo, Japan)[9–12]. RDI has three modes (modes 1–3): mode 1 is suitable for observing the point of bleeding, whereas mode 2 is for detection of deeper blood vessels. Naganuma et al. reported that the severity of inflammation in patients with ulcerative colitis was assessed by using RDI [13]. RDI has been shown to improve the visibility of blood vessels and bleeding points in cases of acute GI bleeding and ESD[14–16]. RDI enables visualization of blood vessels in the deep submucosa. It has been reported that the visibility of esophageal varices is enhanced using RDI[17]. Other studies have reported the usefulness of RDI for endoscopic diagnosis and treatment[14, 18–22].

We previously reported a case in which RDI (mode 2) was effective for detecting exposed blood vessels on a gastric ESD-induced ulcer[19]. In this case, the surround tissues such as submucosal fibrous tissue, fatty tissue, and the muscle layer were identified as a whiter collar using RDI rather than using white light imaging (WLI). RDI visualized the exposed blood vessels more clearly. However, no reports have been published on the quantitative color difference between the exposed vessels and surrounding tissue in gastric ESD-induced ulcers and the visibility of exposed vessels on these ulcers, as observed using RDI. In this study, we conducted a pilot investigation to clarify the quantitative color difference and the visibility of exposed vessels on gastric ESD-induced ulcers observed using RDI. The primary endpoint was color differences (ΔE) between the exposed vessels and surrounding tissue in each modality.

Subjects

All consecutive subjects who underwent gastric ESD between January and March 2021 at Hakodate Municipal Hospital were enrolled. All subjects provided written informed consent before undergoing gastric ESD. Fourteen patients were enrolled in this study, and 64 vessels in gastric ESD-induced ulcers were evaluated using both WLI and RDI. The criteria for gastric ESD were established according to the Japanese Gastric Cancer Association Guideline. This study was performed in accordance with the rules and regulations of the Hakodate Municipal Hospital Institutional Review Board (#2020-94).

ESD procedure

First, marking dots were made using a needle knife around the circumference of the target tumor via observation with a GIF-H290Z with EVIS X1 video system (Olympus Medical Systems, Tokyo, Japan). Subsequently, the endoscope was changed to the therapeutic scope (GIF-H290T with EVIS X1 video system; Olympus Medical Systems, Tokyo, Japan). We injected a mixture of sodium hyaluronate-based submucosal injection material (Ksmart; Olympus Medical Systems, Tokyo, Japan) with 0.5% indigo carmine and 0.1% epinephrine into the submucosal layer. A circumferential incision and submucosal dissection were performed using an electrosurgical knife (IT2 Knife; Olympus Medical Systems, Tokyo, Japan) with a high-frequency generator (VIO3; ERBE, Tubingen, Germany).

Endoscopic treatment and observation of the ulcer after ESD

We changed the scope again to the GIF-H290Z (Olympus Medical Systems, Tokyo, Japan) from the GIF-H290T after dissection was completed. We first observed the ESD-induced ulcer with WLI and then with RDI. We then recorded images of ESD-induced ulcers, as visualized using WLI and RDI. When the exposed vessels were detected, they were coagulated using hemostatic forceps (RAICHO2: Kaneka Medix Corporation, Osaka, Japan) or clipped (Standard clip, HX-600-135; Olympus, Tokyo, Japan) under observation with RDI.

Management after ESD

After ESD, a proton-pump inhibitor (20 mg omeprazole) was intravenously injected twice daily on days 1 and 2. Oral vonoprazan (20 mg/day) was administered from day 3 for a minimum of 8 weeks. A second-look endoscopic examination was performed on days 2 and 7, and when bleeding or exposed blood vessels were detected, hemostasis was achieved using hemostatic forceps or by clipping. We defined delayed bleeding as hematemesis, melena, or anemia (a decline in Hb of 2 g/dL compared with the day before ESD) that required endoscopic treatment.

Image processing and color analysis

The midrange images of the whole ulcer observed using each mode (WLI and RDI) were selected for each ESD-induced ulcer (Fig. 1a and 1b). Two endoscopic specialists who have experience with over 200 gastric ESD procedures, selected the target exposed vessels on ESD-induced ulcers and numbered each exposed blood vessel. The color processing and analysis were performed using Image Pro (Media Cybernetics, Inc., Rockville, Maryland, USA). The color difference was evaluated by comparing the color values of regions of interest (ROI) for an exposed vessel point and three points surrounding an exposed vessel. The three points surrounding exposed vessels were 120° apart from each other. The ROI color in the endoscopic image was assessed using the Commission Internationale de l’Eclairage (CIE) 1976 L*a*b* color space. This is a three-dimensional space for presenting a color. The color values of the exposed vessels (L*v, a*v, and b*v) and the mean of three surrounding points on the mucosa (L*s, a*s, and b*s) were defined as the average of the color value in each ROI using the CIE L*a*b* color space (Fig. 2a and 2b). The color difference between the lesion and the surrounding mucosa (ΔE) is expressed using the following equation:

ΔE = (L*v − L*s)² + (a*v − a*s)² + (b*v − b*s)²

Visibility of exposed vessels on gastric ESD-induced ulcers

Three expert endoscopists (S.M., M.O., and M.H.) scored each image observed using WLI and RDI. The images were the same as those used for the color analysis. As previously described[11, 23, 24], the visibility of each image was rated as follows: +2 (improved visibility), + 1 (somewhat improved visibility), 0 (equivalent to white light), − 1 (somewhat decreased visibility), and − 2 (decreased visibility). We evaluate the total score of the three scores from each image. If an image earned a total score of + 3 or higher, the visibility was considered improved, whereas a score between + 2 and − 2 indicated no change in visibility. The score of − 3 or lower indicated decreased visibility. Interobserver agreement was also assessed using the kappa statistic.

Statistical analysis

The results were analyzed using Prism version 6 (GraphPad Software, Inc., La Jolla, CA, USA). Data are expressed as means ± standard errors of the mean and as medians (interquartile range). Parameters were compared between the two groups between WLI group and RDI group using Student’s t-test. Differences were considered statistically significant when p < 0.05. Interobserver agreement was measured using the kappa statistic.

Fourteen patients were enrolled in this study. One patient had no exposed vessels in the ESD-induced ulcer. The characteristics of the 14 enrolled patients are shown in Table 1. Four patients used aspirin, and one patient was treated with apixaban. The tumor locations were in the upper/middle/lower portions of the stomach in 4/3/7 cases. The characteristics of the ESD-induced ulcers are shown in Table 2. The median dissection area was 676.87 (range 628–1032.8) mm². The median number of exposed vessels on ESD ulcers was 3.5 (2.75–5.25). Procedures performed after ESD were as follows: clipping (0/14), coagulation (8/14), both coagulation and clipping (5/14), and none (1/14). No delayed bleeding was observed.

All 64 exposed vessels in the gastric ESD-induced ulcers were evaluated. The exposed vessels were located in the upper/middle/lower portion of stomach in 13/19/32 cases. The average ΔE values (± SEM) for WLI and RDI were 24.85 (± 1.19) and 31.83 (± 1.31), respectively. The ΔE value for RDI was significantly higher than that for WLI (p < 0.01) (Fig. 3).

The visibility scores are shown in Table 3 Improved visibility was found in 54.7% (35/64) of cases, equivalent visibility was found in 43.8% (28/64) of cases, and decreased visibility was found in 1.7% (1/64) of cases. The kappa value (Fleiss’ kappa) was 0.44.

This is the first study to investigate the visibility and the quantitative color difference between the exposed blood vessels and surrounding tissue in gastric ESD-induced ulcers observed using RDI and WLI. This study revealed that the quantitative color difference observed using RDI was significantly higher than that using WLI. Additionally, 54.7% of exposed vessels on gastric ESD-induced ulcers were visualized more clearly using RDI than using WLI. The submucosal fibrous tissue, fatty tissue, and the muscle layer were identified as a whiter collar using RDI, as opposed to white light, in almost case (Fig. 4). The mean L*, mean a*, and mean b* values of exposed vessels were 23.97/21.97, 17.49/7.19, and 13.45/13.03 for WLI/RDI, respectively. No significant color difference in the exposed vessels was observed between WLI and RDI. On the contrary, the mean L*, mean a*, and mean b* values of the surrounding tissue were 44.38/47.46, 11.72/−6.44, and 19.22/9.96 for WLI/RDI, respectively. A significant color difference was found in the a* and b* values between WLI and RDI in the observation of the surrounding tissue. The color difference between the exposed vessels and surrounding tissue was higher with RDI than with WLI because the color of the surrounding tissue, such as submucosal fibrous tissue, fatty tissue, and the muscle layer, had changed. Some reports have described that the surrounding tissue is whiter in color with RDI compared with WLI. We previously reported a case of hematoma during gastric ESD[18]. The visibility of submucosal fibrous tissue in the submucosal layer was improved by RDI. The submucosal fibrous tissue was observed to be whiter with RDI than with WLI. Ninomiya et al. reported that the effectiveness of RDI for colorectal ESD[11]. The visibility of submucosal vessels and the demarcation line of the muscle layer was improved by RDI. Tanaka et al. reported that submucosal fatty tissue appears as a clear white color in RDI[25].

Several other studies have reported that RDI is useful in ESD because RDI maintains clear visibility in the submucosal layer with fatty tissues during colorectal ESD[25]. Yorita et al. reported that RDI improved the visibility of blood vessels and bleeding points in gastric ESD cases with oozing blood[15]. Fujimoto et al. demonstrated that hemostatic procedures during ESD were safe using RDI[20]. Additionally, RDI reduces the psychological stress experienced by endoscopists. In this study, the procedure time to treat exposed vessels was not examined. However, the procedure time to treat exposed vessels after completed dissection may be shortened with RDI due to the improvement in visibility of exposed vessels on ESD-induced ulcers. This study has some limitations, as it was a retrospective single-center pilot study with a relatively small sample size. This study involved a review of endoscopic images to investigate the visibility of exposed vessels using a scoring system. Thus, a prospective study should be performed to investigate the usefulness of RDI.

The quantitative color difference between the exposed blood vessels and surrounding tissue in gastric ESD-induced ulcers became greater with RDI than with WLI. Additionally, the visibility of exposed blood vessels was improved using RDI.

ESD

Endoscopic submucosal dissection

RDI

Red dichromatic imaging

WLI

White light imaging

CIE

Commission Internationale de l’Eclairage

Ethics approval and consent to participate. The study protocol was done in accordance to the ethical guidelines of the 1975 Helsinki Declaration. This study protocol was approved by the ethics committee of Hakodate Municipal Hospital Institutional Review Board (#2020-94). The written informed consent was obtained from all the participants in the study, which was approved by the ethics committee at our hospital.

Consent for publication

Not applicable.

Availability of data and materials

The dataset generated and analyzed during the study is stored in a securelocalized database but is available from the corresponding author in an anonymous format on reasonable request.

Competing interests

The authors declare that they have no competing interests.

Funding

This work has not been supported by any financial grant.

Author contributions

S. M. and M. O. conceived the study, designed and executed experiments, analyzed data, prepared figures and tables, and wrote the manuscript. R. S., M. H., G. S., L. K., K. S., K. H., S. A., K. K., H. H., K. H., Y. Y., H. N., S. O. and N. S. helped write the manuscript. All the authors had access to the study data, they had reviewed and approved the final manuscript. All authors read and approved the final manuscript.

Acknowledgements

Not applicable.

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Table 1. Characteristics of Patients

Table 2. Characteristics of endoscopic submucosal induced ulcer

Table 3. Visibility of red dichromatic imaging corresponding to white light imaging

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Red dichromatic imaging improved the visibility of exposed blood vessels in gastric ulcer induced by endoscopic submucosal dissection– a pilot study

Status:

Version 1

Abstract

Figures

Background

Methods

Subjects

ESD procedure

Endoscopic treatment and observation of the ulcer after ESD

Management after ESD

Image processing and color analysis

Visibility of exposed vessels on gastric ESD-induced ulcers

Statistical analysis

Results

Discussion

Abbreviations

Declarations

References

Tables

Status:

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