Keywords
Endoscopic resection (ESD, EMRc, ...) - Endoscopic resection (polypectomy, ESD, EMRc,
...) - Non-variceal bleeding
Introduction
The first clips for flexible endoscopy were developed more than 30 years ago for hemostasis
[1]. Since then, through-the-scope (TTS) clips have evolved with increasing indications
for use. Initial clip designs faced challenges regarding ease of use, positioning,
deployment, and retention.
Several brands of TTS clips are currently available on the market [2]. Clip configuration is largely preserved across the different clip models. However,
technical variations exist, including the jaw span of an open clip, shape of distal
prongs, length of clip arms, rotatability, ability to re-open and close the clip to
facilitate repositioning, and handle-related deployment maneuvers. These design variables
can impact clip functionality [3]. There are limited data to guide optimal clip selection and current practice is
largely driven by operator preference and institutional supply chains.
The aim of this comparative study was to assess the efficacy, retention rate, and
safety of three industry-leading TTS clips on tissue that mimics the most common scenarios
faced in clinical practice.
Methods
Study design
A preclinical study was performed using six domestic pigs (weight 35–40 kg). All experiments
followed the American Association for Laboratory Animal Science guidelines [4], and the study protocol was approved by the Institutional Animal Care and Use Committee
(IACUC # A00006854–22) of Mayo Clinic. The three TTS clip models used in the study
were: Assurance (STERIS Endoscopy, Mentor, Ohio, United States), Resolution (Boston
Scientific, Boston, Massachusetts, United States), and SureClip (Micro-Tech Endoscopy,
Ann Arbor, Michigan, United States). These commercially available devices are approved
for use in hemostasis, supplemental closure of luminal perforations, endoscopic marking
and anchoring of jejunal feeding tubes.
Procedures
Each animal underwent three upper endoscopy procedures, including lesion creation
(Day -3), clip deployment (Day 0) and follow up (Day 14) ([Fig. 1]). Prior to each endoscopy, animals were maintained on a liquid diet for 48 hours,
including a clear liquid diet 24 hours prior to the procedure. All procedures were
performed under general anesthesia and orotracheal intubation.
Fig. 1 Study design.
Lesion creation
Hot endoscopic mucosal resection (EMR) was performed 72 hours prior to clip deployment
to simulate fibrotic ulcers. Three lesions were created in a linear fashion using
the band ligation EMR technique along the greater curvature of the gastric body in
each animal. A mixture of 0.9% saline and dilute epinephrine (1:100,000) was injected
into the submucosa. An upper endoscope (GIF-H180, Olympus, Tokyo, Japan) was fitted
with a band ligator device (SmartBand, STERIS Endoscopy, Mentor, OH) and the target
mucosa suctioned into the cap followed by deployment of a single band. The pseudopolyp
was resected underneath the band using a 10-mm hot snare (Lariat Snare, STERIS Endoscopy,
Mentor, Ohio, United States) using pulse cut current at 40 watts (Genii, STERIS Endoscopy,
Mentor, Ohio, Unites States).
On the day of clip deployment, standard cold snare mucosal resection was performed
in the gastric body of each animal using a 10-mm cold snare (Lariat Snare, STERIS
Endoscopy, Mentor, Ohio, United States).
Clip placement
Deployment of each of the three clip models was randomized to a normal gastric fold,
cold snare mucosal resection site, and simulated fibrotic ulcer ([Fig. 2]). A total of nine clips (3 per model) were deployed in each animal ([Fig. 3]). Endoscopists (n=2) were asked to evaluate each clip type by responding to the
statement: overall, I am satisfied with the ease of clip deployment. Responses were
rated on a 5-point Likert scale with: 1=strongly disagree and 5=strongly agree. Follow-up
endoscopy was performed two weeks after clip placement to assess mucosal healing,
and the presence of retained clips for each model and defect type.
Fig. 2 Clip placement on a cold snare resection sites, b fibrotic ulcer sites, and c normal
gastric fold.
Fig. 3 Schematic of a single pig stomach showing three different lesion types and deployed
clips of each model.
Outcomes and statistical analysis
The performance of each TTS clip model was assessed in terms of efficacy, clip retention
and safety. Efficacy was measured by successful clip deployment across the target
site. Tissue closure of cold snare resection sites and fibrotic ulcers was defined
as complete, with no resection or ulcer base visible after clip deployment, or partial,
with visible resection or ulcer base. Mucosal healing was defined as complete reepithelialization
of fibrotic ulcers and cold mucosal resection sites, and clip retention rate was determined
by the number and type of retained clips observed on follow-up endoscopy. Adverse
events (AEs) were documented during the procedure and follow up period. Overall retention
rate and healing rates were calculated for each clip model in all animals, further
stratified by mucosal/defect type. Data were reported as percentages and compared
using Chi-squared analysis, with significance defined as P <0.05.
Results
Band-assisted EMR was successfully performed in all animals prior to clip placement
with resultant fibrotic ulcers. Cold snare mucosal resection was achieved in all animals.
Clips were successfully deployed across all target sites (18 fibrotic ulcers, 18 cold
snare resection sites and 18 normal mucosa) with a total of 54 clips (18 Assurance,
18 Resolution, and 18 SureClip) utilized in six pigs. Tissue defect closure was complete
in all cold resection sites (18/18 sites, 100%) with full mucosal apposition achieved
due to tissue pliability. However, closure was partial in all fibrotic ulcers with
no sites achieving complete closure (0/18 sites, 0%) due to associated tissue firmness
([Fig. 4]).
Fig. 4 Complete tissue closure rate stratified by tissue and clip type.
At week 2, mucosal healing was noted in all sites, regardless of clip model and independent
of whether a clip was retained at the site. Overall clip retention rates were nine
of 18 (50.0%) for SureClip, 10 of 18 (55.6%) for Assurance, and 13 of 18 (72.2%) for
Resolution (P=0.369) ([Table 1]). On a per lesion basis, no differences were noted in SureClip, Assurance, and Resolution
clip retention rates on normal tissue (83.3%, 100% and 83.3%, respectively, P=0.57) or cold snare resection sites (66.7%, 66.7% and 83.3%, respectively, P=0.76). However, retention rate was higher for Resolution clips on fibrotic ulcers
(50.0% vs. 0% for other clips, P=0.03). No AEs, specifically bleeding and perforations, were noted during clip placement,
survival period and follow-up endoscopy. Ease of use was equal across all clip models,
with a mean response of 5 (SD 0) for normal and cold snare resected tissue and mean
response of 1 (SD 0) for fibrotic tissue.
Table 1 Retention rate stratified by tissue and clip type.
|
Sureclip
|
Assurance
|
Resolution
|
P value
|
|
*P <0.05.
EMR, endoscopic mucosal resection.
|
|
Overall
|
9/18 (50.0%)
|
10/18 (55.6%)
|
13/18 (72.2%)
|
0.37
|
|
Normal tissue
|
5/6 (83.3%)
|
6/6 (100.0%)
|
5/6 (83.3%)
|
0.57
|
|
Cold snare resection
|
4/6 (66.7%)
|
4/6 (66.7%)
|
5/6 (83.3%)
|
0.76
|
|
Fibrotic tissue
(hot EMR)
|
0/6 (0%)
|
0/6 (0%)
|
3/6 (50%)
|
0.03*
|
Discussion
Through-the-scope clips are routinely used for hemostasis, repairing mucosal defects,
securing prostheses, and closing fistulas [5]
[6]
[7]. More recently, there has been significant interest in developing and optimizing
endoscopic clips for mucosal apposition after advanced tissue resection procedures,
such as EMR, endoscopic submucosal dissection and peroral endoscopic myotomy [8]
[9]
[10]
[11].
The current literature assessing clip function is limited and consists largely of
benchtop or biomechanical experimental studies [3]
[8]
[12]. The in-vivo comparative studies that have been performed are restricted to normal
mucosa or a single lesion type [13]
[14]
[15]. This study adds to the literature by providing comparative outcomes related to
clip deployment, retention rate, mucosal healing, and ease of use across multiple
tissue types that would be encountered in clinical practice. The results suggest that
overall clip function is preserved across different models. While all clips were deployed,
ease of use was more impacted by the type of tissue rather than the specific type
of device.
There was no significant difference in overall retention rates of the three clips
studied. This is generally consistent with prior data that assessed clip retention
rates at 2 weeks across multiple models [13]
[14]
[16]. When stratified by lesion type, differences were only seen in indurated/fibrotic
tissue where Resolution clips were retained at a significantly higher rate than SureClip
and Assurance. There are some data to support the relatively greater retention rates
of Resolution clips. Shin et al. found higher retention of Resolution clips compared
to TriClip (Cook Medical, Bloomington, Indiana, United States) and HX-5L clips (Olympus,
Tokyo, Japan) at 5 weeks, as did Jensen and colleagues at 5 to 7 weeks [13]
[14]. Swellengrebel et al. reported higher Resolution clip retention rates compared to
QuickClips (Olympus, Tokyo, Japan) at week 12 [17]. However, a retained clip does not necessarily translate into greater clinical efficacy.
One randomized study on chronic ulcers in canines similarly showed higher rates of
Resolution clip retention in fibrotic ulcers, but found no difference in healing when
compared to controls [15]. This is similar to the current study where more Resolution clips remained in-situ
in the fibrotic subgroup, but there was no difference in rates of healing. In fact,
all lesions in our study demonstrated complete reepithelialization by 2 weeks, including
fibrotic ulcers which could only be partially closed.
Limitations of this study include the use of only three clip models and, as such,
results may not be generalized to other TTS clip devices. However, the devices selected
in our study are commonly used in clinical practice. Also, the study did not assess
clip retention rates beyond 2 weeks; however, the 14-day survival period was adequate
to facilitate healing in recently resected tissue as well as fibrotic ulcers. For
TTS clips, there are not many indications that require extended retention rates, aside
from fixation of a stent or feeding tube. In these cases, consideration of clip type
or an alternative device, such as an over-the-scope clip (OTSC), may be more suitable.
Similarly, fistula closure requires a more robust clip, such as the OTSC, or alternative
closure methods. While attempts were made to replicate different tissue types that
would be encountered in clinical practice, the study does not fully duplicate the
diverse indications for which endoscopic clips are currently used. The lack of AEs
and sample size also limits the ability to make definitive conclusions regarding safety.
Conclusions
Ultimately, the model used in clinical practice will be driven by several factors,
including indication, anatomy, operator preference and institutional directives related
to cost and supply chain. The data presented here indicate that minor variations in
clip design do not have significant impact on mucosal healing, overall retention,
and ease of use. Future studies are needed to evaluate cost-effectiveness, which may
impact decision-making when selecting the optimal endoscopic clip.
