Digestive Endoscopy 2015; 27: 106–112
doi: 10.1111/den.12329
Original Article
Utility of a new reusable clip device for endoscopic treatment Satoshi Shinozaki,1,2 Keijiro Sunada,2 Toshiya Otake,2,3 Alan T. Lefor4 and Hironori Yamamoto2 1
Shinozaki Medical Clinic, 2Division of Gastroenterology, Department of Medicine, 4Department of Surgery, Jichi Medical University and 3Department of Gastroenterology, Haga Red Cross Hospital, Tochigi, Japan Background and Aim: Existing reusable endoscopic clip devices have some problems regarding opening the device and precise control of clip application. The aim of the present study was to evaluate reusable clip devices for endoscopic treatment. Methods: Ability to close a large defect and grip force were evaluated using ex-vivo porcine colon. We assessed clip loading and opening in a non-clinical setting and describe the resulting learning curve. To evaluate clinical utility, data for clip application in 72 post-endoscopic mucosal resection (EMR) defects in 40 patients were retrospectively analyzed. Results: There was no difference in the ability to close a 20-mm
Conclusions: ZEOCLIP is more quickly and easily opened to its maximum width compared with EZClip, and is feasible for clip application after EMR.
full-thickness defect and the grip force comparing the new clip device (ZEOCLIP®) and a previously used reusable clip device (EZClip®). Although the time to load the ZEOCLIP was almost same
Key words: clip application, endoscopic mucosal resection (EMR), endoscopic treatment, polypectomy, reusable clip device
INTRODUCTION
E
NDOSCOPIC CLIP DEVICES are widely used for various purposes including marking, hemostasis and closure of perforations or fistulae. The main adverse event after colonoscopic polypectomy is bleeding, which occurs after approximately 1% of procedures, and is usually treated by clip application.1,2 Endoscopic clips were first introduced more than 30 years ago3 and have undergone remarkable improvement, mainly being used in the treatment of nonvariceal bleeding. Currently available clip devices are divided into disposable (single-use) devices and reusable (reloadable) delivery devices with disposable clips.4,5 A single-use, preloaded clip device used in Japan is the Resolution Clip® (Boston Scientific Corporation, Natick, MA, USA) with the ability to be reopened, allowing repositioning of the clip after closing, as
Corresponding: Hironori Yamamoto, Division of Gastroenterology, Department of Medicine, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke, Tochigi 329-0498, Japan. Email: ireef @jichi.ac.jp Received 6 April 2014; accepted 30 June 2014.
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as the EZClip, the time to open the ZEOCLIP was significantly shorter than the EZClip (P < 0.001). Opening width of the ZEOCLIP was significantly wider than the EZClip (P < 0.05). We successfully accomplished closure of post-EMR defects by clip application in 72 lesions using ZEOCLIP. Reopening/repositioning and restoring it to the working channel were more frequently carried out in a noneasy location than in an easy location (11/35 [31%] vs 4/37 [11%], P = 0.030; and 21/35 [60%] vs 1/37 [3%], P < 0.001, respectively).
long as the device has not been fired. In Japan, reusable delivery devices using disposable clips are commercially available, and reusable clip devices (EZClip®; Olympus Corp., Tokyo, Japan) are much more popular than single-use devices. However, there are some difficulties with the available reusable devices including: (i) the greatest width for opening the clip is not always achievable; (ii) inability to reopen and reposition the device; and (iii) inability to restore the device to the working channel or sheath. In 2011, the ZEOCLIP® (Zeon Medical, Tokyo, Japan) was released in Japan. Unlike existing reusable clip devices, this reusable device has a different clip application mechanism that facilitates various functions including: (i) it always achieves the greatest opening width; (ii) it enables reopening and repositioning of the clip multiple times, as long as it has not been fired; and (iii) the design facilitates restoration of the device to the working channel or outer sheath after opening (Table 1). We have used the ZEOCLIP since April 2013 in Haga Red Cross Hospital, and have carried out clip application after endoscopic mucosal resection (EMR) using this device. The aim of the present study was to evaluate the following: (i) ability to close a full-thickness defect using the clip and the
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Table 1 Comparison of reusable clip devices
Clip loading Greatest width and angle Achieving greatest opening width Rotation Reopening and repositioning Restoration to the working channel or outer sheath Signs of firing Price of reusable delivery catheter Price of disposable clips
ZEOCLIP
EZClip
Two steps 10 mm, 90 degrees Always Easy Enabled Enabled No sound 50 000 JPY (≈ USD $500) 750 JPY (≈ USD $7.50)
One step 10 mm, 90 degrees Not always Easy Unable Unable A ‘click’ sound 82 500 JPY (≈ USD $825) 975 JPY (≈ USD $9.75)
JPY, Japanese yen; USD, United States dollars.
grip force tested using an ex-vivo model; (ii) ease of loading a clip and opening it to its greatest width in a non-clinical setting; and (iii) clinical feasibility of using ZEOCLIP to close a post-EMR defect in clinical use.
METHODS
instructions). To apply the clip at the desired location, the clip operator moves the slider proximally until tactile resistance is felt in the handle. After the completing the closure, the clip operator moves the slider distally to release the clip. Then, the clip operator restores the exposed wing-like hook into the outer sheath.
Clip devices
Ex-vivo model
W
To evaluate the ability of the ZEOCLIP to close a large full-thickness defect, we used ex-vivo porcine colon. We also assessed the ability of the EZClip as a control in the same experiment. The resected colon was attached to a soft board using needles. To determine the ability of closing defects comparing the two kinds of clip devices, a standard 20-mm full-thickness defect was made in the porcine colon (Fig. 2a). First, we closed a 20-mm defect using each clip device. We defined ‘success’ as closure of the defect and a fired clip on the mucosa (Fig. 2b). We defined ‘failure’ as when a clip was repelled by the mucosa. Second, we assessed the grip force of the clip after closing the defect. The porcine colon was fixed with a metal fastener. We attached the metal fastener to the ex-vivo colon 20 mm away from the edge of the defect, and pulled the fastener using a spring scale (Fig. 2c), documenting the force applied when the clip detached from the colon.
E USED THE ZEOCLIP reusable clip device (ZP-S195S [reusable delivery catheter] and ZP-CH [standard disposable clip]; Zeon Medical). A different reusable clip device, the EZClip, (HX-110QR [reusable delivery catheter] and HX-610-090 [standard disposable clip]; Olympus) was used as a control. Both devices have a maximal aperture width of 10 mm. The delivery system for the ZEOCLIP consists of a central metal wire, a metal inner sheath and a metal outer sheath. The tip of the metal wire within the inner sheath has a metal wing-like hook, which can catch the proximal side of a disposable clip (Fig. 1a). First, the clip operator loads the clip onto the device (Fig. 1b,c) and stores the clip in the outer sheath. This loading procedure is easily and rapidly accomplished using the applicator (Fig. 1d). Second, the endoscopist inserts the delivery catheter through the working channel. Once the clip device is observed to be exiting the tip of the endoscope, the clip operator pulls the outer sheath to fully expose the clip and inner sheath. If the location is anatomically difficult, the clip operator can restore the clip into the outer sheath and the working channel. When the clip is at the desired location, the clip operator moves the slider proximally to close the clip (Fig. 1e). As the clip-firing mechanism in this new device is different from the EZClip, the clip operator can reopen and reposition the clip multiple times to set the location appropriately at any time before firing (although this feature is not documented in the manufacturer’s
Evaluation of clip loading and opening in a non-clinical setting To assess the operability of clip loading and opening using ZEOCLIP and EZClip, 10 nurses who had not participated in endoscopic clip placement participated in this study in a non-clinical setting. After receiving simple instructions, thenurses loaded the clip onto the device and stored the clip in the outer sheath, and then opened it. We measured loading time, opening time and width between the jaws of the device.
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a
b
c
d
e
Figure 1 Operation of the ZEOCLIP. (a) The delivery catheter with a wing-like hook (left) and the ZEOCLIP (right). (b) The wing-like hook is about to catch the proximal side of the ZEOCLIP. (c) After loading the clip, the metal ring (arrow) is recognized at the proximal side of ZEOCLIP. (d) The wing-like hook is inserted into the applicator. This loading procedure can be easily and rapidly accomplished using this applicator. (e) The metal ring (arrow) is pushed by the inner sheath to close the clip.
Participants repeated the procedure five times and we described the learning curve.
Patients and therapeutic procedures This was a retrospective analysis of patients who underwent clip closure using the ZEOCLIP after EMR. The single exclusion criterion was a large polyp not suitable for EMR. Written informed consent was obtained for colonoscopy and
EMR procedures. Clinical data were obtained from patient medical records, photographs and videos. This study was approved by the Institutional Review Board of Haga Red Cross Hospital. We began using the ZEOCLIP in April 2013. From April to July 2013, 97 EMR were carried out in 53 patients at Haga Red Cross Hospital in the Department of Gastroenterology. We used the ZEOCLIP in 40 of 53 patients in whom 72 EMR procedures were done. The EMR procedure is described
© 2014 The Authors Digestive Endoscopy © 2014 Japan Gastroenterological Endoscopy Society
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b
c
Figure 2 Closing a full-thickness defect and grip force in the ex-vivo model. (a) A standard 20 mm fullthickness defect is made in ex-vivo porcine colon. (b) The defect is closed using ZEOCLIP. (c) Measuring the grip force by pulling the ex-vivo tissue using a spring scale.
elsewhere.6 A colonoscope with a transparent hood at the tip was used. We carried out clip application to close the post-EMR defect in all patients. For the EMR procedure, the location, macroscopic form, and size of the polyp were recorded. Procedure time for clip application, number of clips, reopening/repositioning, restoring to the working channel and difficulty of endoscopic access were also recorded. Post-polypectomy bleeding and antiplatelet/anticoagulant intake was also recorded. When we carried out clip application at a location that was anatomically difficult to access, we sometimes failed and were forced to repeat the procedure. We classified EMR location based on access difficulty into ‘easy location’ and ‘non-easy location’ categories. In the present study, the definition of an ‘easy location’ was: (i) colonoscope did not slip down because of a sharp bend; and (ii) target polyp was easily observed in the visual field (e.g. not behind haustra).
Statistical analysis Categorical data were compared using the Fisher’s exact test, whereas data with a normal distribution were compared using the paired Student’s t-test. Differences were considered to be statistically significant when P < 0.05.
RESULTS Closing a defect and grip force in the ex-vivo model
F
IRST, WE ASSESSED the utility of the ZEOCLIP and EZClip to close a 20-mm full-thickness defect using ex-vivo porcine colon (Fig. 2), repeating the procedure 10 times. To close the defect, there were no differences between the two clip devices tested with regard to success rate (Table 2). Second, we evaluated the grip force after clip application. The grip force of ZEOCLIP and EZClip were both approximately 0.5 newtons, with no significant difference in grip force between the two clips (Table 2). Overall, the ZEOCLIP and EZClip were equal in their ability to close a large defect with similar grip force.
Favorable operability of ZEOCLIP in loading and opening To assess the utility of the ZEOCLIP device, 10 nurses who had never handled a clip device carried out loading and opening of the device five times (Fig. 3). EZClip was tested as a control. No significant differences were recognized in loading time between the ZEOCLIP and EZClip in all procedures, despite different loading mechanisms (Fig. 3a).
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Table 2 Comparison of the ability to close a 20-mm defect and grip force
Closing a 20-mm defect ZEOCLIP EZClip Measurement of the grip force (N: newtons, mean ± SD) ZEOCLIP EZClip
Success
Failure
10 10
0 0
5.60 ± 3.23 4.65 ± 2.47
a (seconds)
P = 1.000
P = 0.471
b
By the fifth repetition of the procedure, the loading time of both types of clip was approximately 7 s (Fig. 3a). Clip opening time for ZEOCLIP was significantly shorter than that of EZClip throughout the five repetitions (P < 0.001 for all procedures). The opening time for ZEOCLIP was approximately 1 s (Fig. 3b). Although the opening time of EZClip became shorter with repetition, the opening time did not reach the same level as ZEOCLIP (Fig. 3b). Next we evaluated the opening width of both clip devices. All participants achieved the greatest width (10 mm) using ZEOCLIP in all procedures, but no-one achieved the greatest width (10 mm) using EZClip the first time. In all procedures, the opening width for EZClip was significantly less than for ZEOCLIP (P < 0.05) (Fig. 3c). Most participants could not recognize the timing of full opening of EZClip the first and second times despite receiving instructions. Although the times for EZClip were improved by training, the results did not reach the same level as that of ZEOCLIP (Fig. 3c).
(seconds)
c
Clinical feasibility of using ZEOCLIP for closing a post-EMR defect We carried out clip application after a total of 72 EMR procedures in 40 patients (Table 3; Fig. 4). In 72 EMR procedures, 35 locations were classified as non-easy and 37 as easy. Mean size of the resected polyps was 7.0 ± 2.9 mm (range, 3–20), and the polyps were mainly located in the sigmoid and ascending colons. En bloc resection was successfully carried out for all polyps. Delayed bleeding or perforation did not occur in any patient. The mean (± SD) number of clips used per post-EMR defect was 1.82 ± 0.89 (range, 1–4). The number of clips used for clip application was proportional to the procedure time for clip application (Table 3). We successfully accomplished closure of all post-EMR defects using ZEOCLIP. Only one of 132 clips (0.8%) failed to be applied during reopening and repositioning. No clips were applied in such a way as to be crossed over each other. The ZEOCLIP can be reopened/repositioned or restored to the working channel because of the design of the device
Figure 3 Use of ZEOCLIP and EZClip in loading and opening in a non-clinical setting. (a) Learning curve for clip loading time of both devices for five repetitions. (b) Learning curve for clip opening time. (c) Learning curve for clip opening width. *P < 0.05, ** P < 0.001.
(although not described in the manufacturer’s instructions). We frequently took advantage of this feature in locations that were anatomically difficult to access. In non-easy locations, the clip operator and endoscopist tried to adjust the opened clip to the desired position by reopening/repositioning and tried to avoid mucosal damage by restoring the device to the working channel. Reopening/repositioning was significantly more frequently carried out in non-easy locations than in easy locations (11/35 [31%] vs 4/37 [11%], P = 0.030). Restoring the device to the working channel was also significantly more
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Table 3 Clinical characteristics of patients, colorectal polyps and clip application Patients, n Age (mean ± SD) (years) Gender (male/female) Lesions, n Size (mean ± SD), mm Shape (sessile/pedunculated) Distribution (rectum, sigmoid, descending, transverse, ascending, cecum) Difficulty of the location (easy/non-easy) Time for clip application (s) 1 clip (n = 31) 2 clips (n = 28) 3 clips (n = 8) 4 clips (n = 5)
a
40 67.6 ± 11.4 27/13 72 7.0 ± 2.9 68/4 2, 25, 6, 19, 16, 4
37/35
48.6 ± 23.4 150.6 ± 50.4 191.8 ± 53.8 267.4 ± 33.0
b
frequently carried out in non-easy locations than in easy locations (21/35 [60%] vs 1/37 [3%], P < 0.001).
DISCUSSION
I
N THE PRESENT study, the ZEOCLIP had a greater ability for closing a large full-thickness defect, favorable operability in regard to opening and clinical feasibility of clip closure of post-EMR defects in 72 EMR procedures in 40 patients. This was particularly true in locations difficult to access anatomically. The ZEOCLIP was readily reopened/ repositioned or restored to the working channel. To complete a post-EMR defect closure, appropriate positioning and safety are very important. Even if the post-EMR defect is located in an anatomically difficult-to-access location, mucosal injury or perforation caused by sharp clip jaws must be avoided. These data reveal that reopening/ repositioning or restoring the device to the working channel was frequently needed in non-easy locations, and suggest that ZEOCLIP may help prevent mucosal injury or perforation. Among the adverse events associated with endoscopy, a perforation defect caused by the use of the endoscope or device must be closed adequately. In this emergency situation, clip closure of the perforation defect must first be successfully accomplished. Even if the location is endoscopically difficult to access, rapid and accurate clip application is essential. Failure of the clip to fire correctly may result in enlargement of the defect with resultant leak. Having a short opening time and the ability to readily open to the greatest width, the ZEOCLIP facilitates clip application in this situation. When endoscopists carry out perforation closure and hemostasis, treatment must be accomplished in a short time in a tense
c
Figure 4 (a) Colonoscopic view of a sessile polyp in the transverse colon. (b) Post-endoscopic mucosal resection defect. (c) Three clips (ZEOCLIP) are successfully applied to close the defect.
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atmosphere. A simple and rapid clip opening procedure may make a difference in such situations. We documented successful closure of a full-thickness defect using an ex-vivo animal model using both clips. However, we must be cautious in our interpretation as this was carried out with ex-vivo tissue, which may behave differently to living tissue. An in-vivo animal model may be more useful to evaluate comparison of clips for perforation closure in a future study. ZEOCLIP, the new device described here, has superiority with regard to a short opening time, reopening and repositioning, restoration of the device to the working channel or outer sheath, and cost-effectiveness compared with EZClip (Table 1). EZClip has superiority with regard to its simple procedure of clip loading and for its clear ‘click’ sound at the time of firing. In the present study, there was no difference in the loading time between ZEOCLIP and EZClip despite the different loading mechanisms. ZEOCLIP had a shorter opening time than EZClip and a certain full-opening ability. Although the opening time and the opening width of EZClip was improved by training, the results did not reach the same level as that of ZEOCLIP. The opening procedure for ZEOCLIP was just one step, as the clip operator pulled the outer sheath to expose the clip and inner sheath. There was a fairly complicated procedure needed when opening the EZClip including: (i) the clip operator exposed the root of the closed clip by pushing a handle; and (ii) the clip operator then pulled the handle slowly and carefully to open the clip, after which the clip operator stopped pulling the handle at the appropriate position to achieve the greatest width. If the clip operator pulled the handle strongly, the clip reclosed and passed through the point of greatest width and could not be reopened. Once the EZClip device was restored to the working channel, its width was narrowed and it could not be reopened to its greatest width. In this situation, the clip operator had to use that clip with a somewhat narrow width, or the narrowed clip could be disposed of before firing. Therefore, ZEOCLIP facilitated clip application in limited and tense moments as well as safely accomplishing endoscopic treatment. Recently, some preloaded, disposable endoclip-fixing devices have been widely used. These disposable devices require neither clip loading nor sterilization. However, single-use disposable devices are considered fairly expensive at approximately JPY 9000 (about USD $90) per device. Although ZEOCLIP is a reusable device, it provides almost similar functionality to that of a single-use disposable device. We believe that the ZEOCLIP will be a mainstay among endoscopic clip devices. In the present study, we presented favorable operating characteristics and clinical feasibility of using ZEOCLIP. These preferable characteristics of ZEOCLIP can be applied to endoscopic hemostasis
Digestive Endoscopy 2015; 27: 106–112
and closure of perforations or fistulas. Further study is necessary to demonstrate the effectiveness of ZEOCLIP for other purposes. We recognize that the present study has limitations including: (i) the retrospective nature of the clinical study; (ii) the study did not incorporate a control group of patients who underwent clip application using different kinds of clip devices; and (iii) the ability of closing a defect was assessed only with ex-vivo tissue. In conclusion, the ZEOCLIP is useful for closing large defects and is readily opened to a maximum clip width. Further, ZEOCLIP is feasible for clip closure of a post-EMR defect and facilitates clip application in lesions at anatomically difficult locations.
ACKNOWLEDGMENTS
T
HE AUTHORS THANK the doctors and nurses of Haga Red Cross Hospital and Shinozaki Medical Clinic for their excellent technical assistance, cooperation and insightful discussions.
CONFLICT OF INTERESTS
A
UTHOR H.Y. HAS a consultant relationship in FUJIFILM Corporation and has received honoraria, grants and royalties from the company. He has patents for doubleballoon endoscope and ESD devices produced by FUJIFILM Corporation. The funding source had no role in the design, practice or analysis of this study. Authors S.S., K.S., T.O. and A.L. declare no conflict of interests for this article. No funding was provided for this study.
REFERENCES 1 Gibbs DH, Opelka FG, Beck DE, Hicks TC, Timmcke AE, Gathright JB, Jr. Postpolypectomy colonic hemorrhage. Dis. Colon Rectum 1996; 39: 806–10. 2 Shioji K, Suzuki Y, Kobayashi M et al. Prophylactic clip application does not decrease delayed bleeding after colonoscopic polypectomy. Gastrointest. Endosc. 2003; 57: 691–4. 3 Hayashi T, Yonezawa M, Kawabara T. The study on staunch clip for the treatment by endoscopy. Gastroenterol Endosc. 1975; 17: 92–101. 4 Grupka MJ, Benson J. Endoscopic clipping. J. Dig. Dis. 2008; 9: 72–8. 5 Raju GS, Gajula L. Endoclips for GI endoscopy. Gastrointest. Endosc. 2004; 59: 267–79. 6 Su MY, Hsu CM, Ho YP et al. Endoscopic mucosal resection for colonic non-polypoid neoplasms. Am. J. Gastroenterol. 2005; 100: 2174–9.
© 2014 The Authors Digestive Endoscopy © 2014 Japan Gastroenterological Endoscopy Society
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doi: 10.1111/den.12329
Original Article
Utility of a new reusable clip device for endoscopic treatment Satoshi Shinozaki,1,2 Keijiro Sunada,2 Toshiya Otake,2,3 Alan T. Lefor4 and Hironori Yamamoto2 1
Shinozaki Medical Clinic, 2Division of Gastroenterology, Department of Medicine, 4Department of Surgery, Jichi Medical University and 3Department of Gastroenterology, Haga Red Cross Hospital, Tochigi, Japan Background and Aim: Existing reusable endoscopic clip devices have some problems regarding opening the device and precise control of clip application. The aim of the present study was to evaluate reusable clip devices for endoscopic treatment. Methods: Ability to close a large defect and grip force were evaluated using ex-vivo porcine colon. We assessed clip loading and opening in a non-clinical setting and describe the resulting learning curve. To evaluate clinical utility, data for clip application in 72 post-endoscopic mucosal resection (EMR) defects in 40 patients were retrospectively analyzed. Results: There was no difference in the ability to close a 20-mm
Conclusions: ZEOCLIP is more quickly and easily opened to its maximum width compared with EZClip, and is feasible for clip application after EMR.
full-thickness defect and the grip force comparing the new clip device (ZEOCLIP®) and a previously used reusable clip device (EZClip®). Although the time to load the ZEOCLIP was almost same
Key words: clip application, endoscopic mucosal resection (EMR), endoscopic treatment, polypectomy, reusable clip device
INTRODUCTION
E
NDOSCOPIC CLIP DEVICES are widely used for various purposes including marking, hemostasis and closure of perforations or fistulae. The main adverse event after colonoscopic polypectomy is bleeding, which occurs after approximately 1% of procedures, and is usually treated by clip application.1,2 Endoscopic clips were first introduced more than 30 years ago3 and have undergone remarkable improvement, mainly being used in the treatment of nonvariceal bleeding. Currently available clip devices are divided into disposable (single-use) devices and reusable (reloadable) delivery devices with disposable clips.4,5 A single-use, preloaded clip device used in Japan is the Resolution Clip® (Boston Scientific Corporation, Natick, MA, USA) with the ability to be reopened, allowing repositioning of the clip after closing, as
Corresponding: Hironori Yamamoto, Division of Gastroenterology, Department of Medicine, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke, Tochigi 329-0498, Japan. Email: ireef @jichi.ac.jp Received 6 April 2014; accepted 30 June 2014.
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as the EZClip, the time to open the ZEOCLIP was significantly shorter than the EZClip (P < 0.001). Opening width of the ZEOCLIP was significantly wider than the EZClip (P < 0.05). We successfully accomplished closure of post-EMR defects by clip application in 72 lesions using ZEOCLIP. Reopening/repositioning and restoring it to the working channel were more frequently carried out in a noneasy location than in an easy location (11/35 [31%] vs 4/37 [11%], P = 0.030; and 21/35 [60%] vs 1/37 [3%], P < 0.001, respectively).
long as the device has not been fired. In Japan, reusable delivery devices using disposable clips are commercially available, and reusable clip devices (EZClip®; Olympus Corp., Tokyo, Japan) are much more popular than single-use devices. However, there are some difficulties with the available reusable devices including: (i) the greatest width for opening the clip is not always achievable; (ii) inability to reopen and reposition the device; and (iii) inability to restore the device to the working channel or sheath. In 2011, the ZEOCLIP® (Zeon Medical, Tokyo, Japan) was released in Japan. Unlike existing reusable clip devices, this reusable device has a different clip application mechanism that facilitates various functions including: (i) it always achieves the greatest opening width; (ii) it enables reopening and repositioning of the clip multiple times, as long as it has not been fired; and (iii) the design facilitates restoration of the device to the working channel or outer sheath after opening (Table 1). We have used the ZEOCLIP since April 2013 in Haga Red Cross Hospital, and have carried out clip application after endoscopic mucosal resection (EMR) using this device. The aim of the present study was to evaluate the following: (i) ability to close a full-thickness defect using the clip and the
© 2014 The Authors Digestive Endoscopy © 2014 Japan Gastroenterological Endoscopy Society
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Table 1 Comparison of reusable clip devices
Clip loading Greatest width and angle Achieving greatest opening width Rotation Reopening and repositioning Restoration to the working channel or outer sheath Signs of firing Price of reusable delivery catheter Price of disposable clips
ZEOCLIP
EZClip
Two steps 10 mm, 90 degrees Always Easy Enabled Enabled No sound 50 000 JPY (≈ USD $500) 750 JPY (≈ USD $7.50)
One step 10 mm, 90 degrees Not always Easy Unable Unable A ‘click’ sound 82 500 JPY (≈ USD $825) 975 JPY (≈ USD $9.75)
JPY, Japanese yen; USD, United States dollars.
grip force tested using an ex-vivo model; (ii) ease of loading a clip and opening it to its greatest width in a non-clinical setting; and (iii) clinical feasibility of using ZEOCLIP to close a post-EMR defect in clinical use.
METHODS
instructions). To apply the clip at the desired location, the clip operator moves the slider proximally until tactile resistance is felt in the handle. After the completing the closure, the clip operator moves the slider distally to release the clip. Then, the clip operator restores the exposed wing-like hook into the outer sheath.
Clip devices
Ex-vivo model
W
To evaluate the ability of the ZEOCLIP to close a large full-thickness defect, we used ex-vivo porcine colon. We also assessed the ability of the EZClip as a control in the same experiment. The resected colon was attached to a soft board using needles. To determine the ability of closing defects comparing the two kinds of clip devices, a standard 20-mm full-thickness defect was made in the porcine colon (Fig. 2a). First, we closed a 20-mm defect using each clip device. We defined ‘success’ as closure of the defect and a fired clip on the mucosa (Fig. 2b). We defined ‘failure’ as when a clip was repelled by the mucosa. Second, we assessed the grip force of the clip after closing the defect. The porcine colon was fixed with a metal fastener. We attached the metal fastener to the ex-vivo colon 20 mm away from the edge of the defect, and pulled the fastener using a spring scale (Fig. 2c), documenting the force applied when the clip detached from the colon.
E USED THE ZEOCLIP reusable clip device (ZP-S195S [reusable delivery catheter] and ZP-CH [standard disposable clip]; Zeon Medical). A different reusable clip device, the EZClip, (HX-110QR [reusable delivery catheter] and HX-610-090 [standard disposable clip]; Olympus) was used as a control. Both devices have a maximal aperture width of 10 mm. The delivery system for the ZEOCLIP consists of a central metal wire, a metal inner sheath and a metal outer sheath. The tip of the metal wire within the inner sheath has a metal wing-like hook, which can catch the proximal side of a disposable clip (Fig. 1a). First, the clip operator loads the clip onto the device (Fig. 1b,c) and stores the clip in the outer sheath. This loading procedure is easily and rapidly accomplished using the applicator (Fig. 1d). Second, the endoscopist inserts the delivery catheter through the working channel. Once the clip device is observed to be exiting the tip of the endoscope, the clip operator pulls the outer sheath to fully expose the clip and inner sheath. If the location is anatomically difficult, the clip operator can restore the clip into the outer sheath and the working channel. When the clip is at the desired location, the clip operator moves the slider proximally to close the clip (Fig. 1e). As the clip-firing mechanism in this new device is different from the EZClip, the clip operator can reopen and reposition the clip multiple times to set the location appropriately at any time before firing (although this feature is not documented in the manufacturer’s
Evaluation of clip loading and opening in a non-clinical setting To assess the operability of clip loading and opening using ZEOCLIP and EZClip, 10 nurses who had not participated in endoscopic clip placement participated in this study in a non-clinical setting. After receiving simple instructions, thenurses loaded the clip onto the device and stored the clip in the outer sheath, and then opened it. We measured loading time, opening time and width between the jaws of the device.
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a
b
c
d
e
Figure 1 Operation of the ZEOCLIP. (a) The delivery catheter with a wing-like hook (left) and the ZEOCLIP (right). (b) The wing-like hook is about to catch the proximal side of the ZEOCLIP. (c) After loading the clip, the metal ring (arrow) is recognized at the proximal side of ZEOCLIP. (d) The wing-like hook is inserted into the applicator. This loading procedure can be easily and rapidly accomplished using this applicator. (e) The metal ring (arrow) is pushed by the inner sheath to close the clip.
Participants repeated the procedure five times and we described the learning curve.
Patients and therapeutic procedures This was a retrospective analysis of patients who underwent clip closure using the ZEOCLIP after EMR. The single exclusion criterion was a large polyp not suitable for EMR. Written informed consent was obtained for colonoscopy and
EMR procedures. Clinical data were obtained from patient medical records, photographs and videos. This study was approved by the Institutional Review Board of Haga Red Cross Hospital. We began using the ZEOCLIP in April 2013. From April to July 2013, 97 EMR were carried out in 53 patients at Haga Red Cross Hospital in the Department of Gastroenterology. We used the ZEOCLIP in 40 of 53 patients in whom 72 EMR procedures were done. The EMR procedure is described
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a
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b
c
Figure 2 Closing a full-thickness defect and grip force in the ex-vivo model. (a) A standard 20 mm fullthickness defect is made in ex-vivo porcine colon. (b) The defect is closed using ZEOCLIP. (c) Measuring the grip force by pulling the ex-vivo tissue using a spring scale.
elsewhere.6 A colonoscope with a transparent hood at the tip was used. We carried out clip application to close the post-EMR defect in all patients. For the EMR procedure, the location, macroscopic form, and size of the polyp were recorded. Procedure time for clip application, number of clips, reopening/repositioning, restoring to the working channel and difficulty of endoscopic access were also recorded. Post-polypectomy bleeding and antiplatelet/anticoagulant intake was also recorded. When we carried out clip application at a location that was anatomically difficult to access, we sometimes failed and were forced to repeat the procedure. We classified EMR location based on access difficulty into ‘easy location’ and ‘non-easy location’ categories. In the present study, the definition of an ‘easy location’ was: (i) colonoscope did not slip down because of a sharp bend; and (ii) target polyp was easily observed in the visual field (e.g. not behind haustra).
Statistical analysis Categorical data were compared using the Fisher’s exact test, whereas data with a normal distribution were compared using the paired Student’s t-test. Differences were considered to be statistically significant when P < 0.05.
RESULTS Closing a defect and grip force in the ex-vivo model
F
IRST, WE ASSESSED the utility of the ZEOCLIP and EZClip to close a 20-mm full-thickness defect using ex-vivo porcine colon (Fig. 2), repeating the procedure 10 times. To close the defect, there were no differences between the two clip devices tested with regard to success rate (Table 2). Second, we evaluated the grip force after clip application. The grip force of ZEOCLIP and EZClip were both approximately 0.5 newtons, with no significant difference in grip force between the two clips (Table 2). Overall, the ZEOCLIP and EZClip were equal in their ability to close a large defect with similar grip force.
Favorable operability of ZEOCLIP in loading and opening To assess the utility of the ZEOCLIP device, 10 nurses who had never handled a clip device carried out loading and opening of the device five times (Fig. 3). EZClip was tested as a control. No significant differences were recognized in loading time between the ZEOCLIP and EZClip in all procedures, despite different loading mechanisms (Fig. 3a).
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Table 2 Comparison of the ability to close a 20-mm defect and grip force
Closing a 20-mm defect ZEOCLIP EZClip Measurement of the grip force (N: newtons, mean ± SD) ZEOCLIP EZClip
Success
Failure
10 10
0 0
5.60 ± 3.23 4.65 ± 2.47
a (seconds)
P = 1.000
P = 0.471
b
By the fifth repetition of the procedure, the loading time of both types of clip was approximately 7 s (Fig. 3a). Clip opening time for ZEOCLIP was significantly shorter than that of EZClip throughout the five repetitions (P < 0.001 for all procedures). The opening time for ZEOCLIP was approximately 1 s (Fig. 3b). Although the opening time of EZClip became shorter with repetition, the opening time did not reach the same level as ZEOCLIP (Fig. 3b). Next we evaluated the opening width of both clip devices. All participants achieved the greatest width (10 mm) using ZEOCLIP in all procedures, but no-one achieved the greatest width (10 mm) using EZClip the first time. In all procedures, the opening width for EZClip was significantly less than for ZEOCLIP (P < 0.05) (Fig. 3c). Most participants could not recognize the timing of full opening of EZClip the first and second times despite receiving instructions. Although the times for EZClip were improved by training, the results did not reach the same level as that of ZEOCLIP (Fig. 3c).
(seconds)
c
Clinical feasibility of using ZEOCLIP for closing a post-EMR defect We carried out clip application after a total of 72 EMR procedures in 40 patients (Table 3; Fig. 4). In 72 EMR procedures, 35 locations were classified as non-easy and 37 as easy. Mean size of the resected polyps was 7.0 ± 2.9 mm (range, 3–20), and the polyps were mainly located in the sigmoid and ascending colons. En bloc resection was successfully carried out for all polyps. Delayed bleeding or perforation did not occur in any patient. The mean (± SD) number of clips used per post-EMR defect was 1.82 ± 0.89 (range, 1–4). The number of clips used for clip application was proportional to the procedure time for clip application (Table 3). We successfully accomplished closure of all post-EMR defects using ZEOCLIP. Only one of 132 clips (0.8%) failed to be applied during reopening and repositioning. No clips were applied in such a way as to be crossed over each other. The ZEOCLIP can be reopened/repositioned or restored to the working channel because of the design of the device
Figure 3 Use of ZEOCLIP and EZClip in loading and opening in a non-clinical setting. (a) Learning curve for clip loading time of both devices for five repetitions. (b) Learning curve for clip opening time. (c) Learning curve for clip opening width. *P < 0.05, ** P < 0.001.
(although not described in the manufacturer’s instructions). We frequently took advantage of this feature in locations that were anatomically difficult to access. In non-easy locations, the clip operator and endoscopist tried to adjust the opened clip to the desired position by reopening/repositioning and tried to avoid mucosal damage by restoring the device to the working channel. Reopening/repositioning was significantly more frequently carried out in non-easy locations than in easy locations (11/35 [31%] vs 4/37 [11%], P = 0.030). Restoring the device to the working channel was also significantly more
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Table 3 Clinical characteristics of patients, colorectal polyps and clip application Patients, n Age (mean ± SD) (years) Gender (male/female) Lesions, n Size (mean ± SD), mm Shape (sessile/pedunculated) Distribution (rectum, sigmoid, descending, transverse, ascending, cecum) Difficulty of the location (easy/non-easy) Time for clip application (s) 1 clip (n = 31) 2 clips (n = 28) 3 clips (n = 8) 4 clips (n = 5)
a
40 67.6 ± 11.4 27/13 72 7.0 ± 2.9 68/4 2, 25, 6, 19, 16, 4
37/35
48.6 ± 23.4 150.6 ± 50.4 191.8 ± 53.8 267.4 ± 33.0
b
frequently carried out in non-easy locations than in easy locations (21/35 [60%] vs 1/37 [3%], P < 0.001).
DISCUSSION
I
N THE PRESENT study, the ZEOCLIP had a greater ability for closing a large full-thickness defect, favorable operability in regard to opening and clinical feasibility of clip closure of post-EMR defects in 72 EMR procedures in 40 patients. This was particularly true in locations difficult to access anatomically. The ZEOCLIP was readily reopened/ repositioned or restored to the working channel. To complete a post-EMR defect closure, appropriate positioning and safety are very important. Even if the post-EMR defect is located in an anatomically difficult-to-access location, mucosal injury or perforation caused by sharp clip jaws must be avoided. These data reveal that reopening/ repositioning or restoring the device to the working channel was frequently needed in non-easy locations, and suggest that ZEOCLIP may help prevent mucosal injury or perforation. Among the adverse events associated with endoscopy, a perforation defect caused by the use of the endoscope or device must be closed adequately. In this emergency situation, clip closure of the perforation defect must first be successfully accomplished. Even if the location is endoscopically difficult to access, rapid and accurate clip application is essential. Failure of the clip to fire correctly may result in enlargement of the defect with resultant leak. Having a short opening time and the ability to readily open to the greatest width, the ZEOCLIP facilitates clip application in this situation. When endoscopists carry out perforation closure and hemostasis, treatment must be accomplished in a short time in a tense
c
Figure 4 (a) Colonoscopic view of a sessile polyp in the transverse colon. (b) Post-endoscopic mucosal resection defect. (c) Three clips (ZEOCLIP) are successfully applied to close the defect.
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atmosphere. A simple and rapid clip opening procedure may make a difference in such situations. We documented successful closure of a full-thickness defect using an ex-vivo animal model using both clips. However, we must be cautious in our interpretation as this was carried out with ex-vivo tissue, which may behave differently to living tissue. An in-vivo animal model may be more useful to evaluate comparison of clips for perforation closure in a future study. ZEOCLIP, the new device described here, has superiority with regard to a short opening time, reopening and repositioning, restoration of the device to the working channel or outer sheath, and cost-effectiveness compared with EZClip (Table 1). EZClip has superiority with regard to its simple procedure of clip loading and for its clear ‘click’ sound at the time of firing. In the present study, there was no difference in the loading time between ZEOCLIP and EZClip despite the different loading mechanisms. ZEOCLIP had a shorter opening time than EZClip and a certain full-opening ability. Although the opening time and the opening width of EZClip was improved by training, the results did not reach the same level as that of ZEOCLIP. The opening procedure for ZEOCLIP was just one step, as the clip operator pulled the outer sheath to expose the clip and inner sheath. There was a fairly complicated procedure needed when opening the EZClip including: (i) the clip operator exposed the root of the closed clip by pushing a handle; and (ii) the clip operator then pulled the handle slowly and carefully to open the clip, after which the clip operator stopped pulling the handle at the appropriate position to achieve the greatest width. If the clip operator pulled the handle strongly, the clip reclosed and passed through the point of greatest width and could not be reopened. Once the EZClip device was restored to the working channel, its width was narrowed and it could not be reopened to its greatest width. In this situation, the clip operator had to use that clip with a somewhat narrow width, or the narrowed clip could be disposed of before firing. Therefore, ZEOCLIP facilitated clip application in limited and tense moments as well as safely accomplishing endoscopic treatment. Recently, some preloaded, disposable endoclip-fixing devices have been widely used. These disposable devices require neither clip loading nor sterilization. However, single-use disposable devices are considered fairly expensive at approximately JPY 9000 (about USD $90) per device. Although ZEOCLIP is a reusable device, it provides almost similar functionality to that of a single-use disposable device. We believe that the ZEOCLIP will be a mainstay among endoscopic clip devices. In the present study, we presented favorable operating characteristics and clinical feasibility of using ZEOCLIP. These preferable characteristics of ZEOCLIP can be applied to endoscopic hemostasis
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and closure of perforations or fistulas. Further study is necessary to demonstrate the effectiveness of ZEOCLIP for other purposes. We recognize that the present study has limitations including: (i) the retrospective nature of the clinical study; (ii) the study did not incorporate a control group of patients who underwent clip application using different kinds of clip devices; and (iii) the ability of closing a defect was assessed only with ex-vivo tissue. In conclusion, the ZEOCLIP is useful for closing large defects and is readily opened to a maximum clip width. Further, ZEOCLIP is feasible for clip closure of a post-EMR defect and facilitates clip application in lesions at anatomically difficult locations.
ACKNOWLEDGMENTS
T
HE AUTHORS THANK the doctors and nurses of Haga Red Cross Hospital and Shinozaki Medical Clinic for their excellent technical assistance, cooperation and insightful discussions.
CONFLICT OF INTERESTS
A
UTHOR H.Y. HAS a consultant relationship in FUJIFILM Corporation and has received honoraria, grants and royalties from the company. He has patents for doubleballoon endoscope and ESD devices produced by FUJIFILM Corporation. The funding source had no role in the design, practice or analysis of this study. Authors S.S., K.S., T.O. and A.L. declare no conflict of interests for this article. No funding was provided for this study.
REFERENCES 1 Gibbs DH, Opelka FG, Beck DE, Hicks TC, Timmcke AE, Gathright JB, Jr. Postpolypectomy colonic hemorrhage. Dis. Colon Rectum 1996; 39: 806–10. 2 Shioji K, Suzuki Y, Kobayashi M et al. Prophylactic clip application does not decrease delayed bleeding after colonoscopic polypectomy. Gastrointest. Endosc. 2003; 57: 691–4. 3 Hayashi T, Yonezawa M, Kawabara T. The study on staunch clip for the treatment by endoscopy. Gastroenterol Endosc. 1975; 17: 92–101. 4 Grupka MJ, Benson J. Endoscopic clipping. J. Dig. Dis. 2008; 9: 72–8. 5 Raju GS, Gajula L. Endoclips for GI endoscopy. Gastrointest. Endosc. 2004; 59: 267–79. 6 Su MY, Hsu CM, Ho YP et al. Endoscopic mucosal resection for colonic non-polypoid neoplasms. Am. J. Gastroenterol. 2005; 100: 2174–9.
© 2014 The Authors Digestive Endoscopy © 2014 Japan Gastroenterological Endoscopy Society
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