Efficacy of innovative polyglycolic acid sheet device delivery station system: a randomized prospective study

Efficacy of innovative polyglycolic acid sheet device delivery station system: a randomized... Background Although there have been several reports of treating large post-endoscopic submucosal dissection (ESD) ulcers by covering them with a polyglycolic acid sheet (PGAs), this approach presents problems regarding PGAs delivery. This study assessed the usefulness of a device delivery station system (DDSS) to evaluate the appropriate and rapid PGAs coat- ing method with DDSS. Methods Thirty-nine of 41 patients who were diagnosed with early gastric cancer over 20 mm in diameter and pathologi- cally diagnosed with well-differentiated adenocarcinoma were randomly allocated to the following two groups according to delivery method: the conventional PGAs delivery group (C group) (n = 19) and the new DDSS group (DDSS group) (n = 20). The primary outcome was the coating area per minute in the C group and DDSS group (cm /min). Results There were significant differences in the coating time (min), with values of 34.1 (15.0–60.7) vs. 16.85 (11.5–27.2) min for the C group and DDSS group, respectively (p = 0.001). There was also a significant difference in coating area per minute, with values of 0.261 (0.02–1.00) and 0.96 (0.173–2.06) cm /min for the C group and DDSS group, respectively (p = 0.001). There were four cases of post-ESD bleeding (1–7 days after ESD) in the C group compared with 0 in the DDSS group, which represented a significant difference (p = 0.030). Conclusions The DDSS was very useful for rapidly delivering and tightly attaching a PGAs to control post-ESD bleeding. Trial registration University Hospital Medical Network (UMIN) 000026377. Keywords Delivery of polyglycolic acid sheet · Coating area per minute · Post-endoscopic submucosal dissection bleeding · Device delivery station system There have been several reports of treatments for large, an over-the-scope clip (OTSC) system (Ovesco Endoscopy artificial post-endoscopic submucosal dissection (ESD) GmbH, Tüebingen, Germany) [1] and covering an ulcer ulcers, such as natural ulcer healing, ulcer closure using with a polyglycolic acid sheet (PGAs) (Gunze Co., Kyoto, Japan); treatment with a PGAs has been used in particular to prevent post-ESD bleeding [2, 3]. Although mechanical Electronic supplementary material The online version of this means of closing larger and deeper mucosal defects via a article (https://doi.org/10.1007/s00464-017-6019-6) contains hemoclip or OTSC system, which reach deeper, submucosal supplementary material, which is available to authorized users. layers after ESD, effectively prevent post-ESD bleeding or * Hirohito Mori delayed perforation to some extent, such mechanical clo- hiro4884@med.kagawa-u.ac.jp sures create a mucosal bridge over the remaining muscu- lar layer when applied without a coating or covering for Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki, larger, deeper defects reaching submucosal layers. Filling Kita, Kagawa 761-0793, Japan and covering a large, deep defect with a PGAs is a more Department of Pharmacology, Kagawa University, 1750-1 natural and effective way for treating large post-ESD arti- Ikenobe, Miki, Kita, Kagawa 761-0793, Japan ficial ulcers to prevent post-ESD adverse events, such as Department of Gastroenterological Surgery, Ehime bleeding and perforation. It is especially difficult to close Rosai Hospital, 13-27, Minamikomatsubara, Niihama, artificial ulcers ≥ 5 cm using a hemoclip or OTSC closure. Ehime 792-8550, Japan Vol:.(1234567890) 1 3 Surgical Endoscopy (2018) 32:3076–3086 3077 As such, filling and covering large artificial defects with a Patients and methods PGAs is a more ideal treatment approach; however, it is dif- ficult to deliver and thoroughly cover an ulcer floor with This study was conducted with approval from the ethics a thin PGAs using only a pan-endoscope, especially under committees of the Ehime Rosai and Kagawa University wet conditions. PGAs delivery is one of the main problems Hospitals (Approval No. 80) and in accordance with the of treating artificial ulcers. The conventional PGAs coating Declaration of Helsinki. The patients provided verbal and method is very time consuming and causes maneuverability written informed consent. This trial was also registered difficulties [4 –8]. As a 30- to 40-mm square-shaped PGAs is with the University Hospital Medical Information Network gripped by grasping forceps through the endoscopic channel (UMIN000026377) following the CONSORT check list. and delivered from the mouth to the stomach along with the Forty-one patients who were diagnosed with early gastric endoscope, the PGAs is exposed to saliva and gastric juices, cancer over 20 mm in diameter by narrow band imaging and it is difficult for the PGAs to maintain its sheet shape magnified endoscopic examination (NBI-ME) and patho- under such wet conditions. Once a PGAs becomes curled up logically diagnosed with well-differentiated adenocarcinoma in the stomach, it is very difficult if not impossible to uncurl from biopsy specimens were eligible for this prospective the PGAs into its sheet form using an endoscope [9, 10]. randomized study. Two patients refused to participate and This study aimed to evaluate the efficacy of appropriate and were excluded. The remaining 39 patients were randomly rapid PGAs coating method using device delivery station allocated using the sealed envelope method into the follow- system (DDSS). ing two groups according to the delivery method: the con- ventional PGAs delivery group (n = 19) (C group) and the new DDSS group (n = 20) (DDSS group) (Fig. 1). Patients taking ticlopidine hydrochloride, clopidogrel sulfate or Fig. 1 Flow chart of this study 1 3 3078 Surgical Endoscopy (2018) 32:3076–3086 aspirin were switched to cilostazol 3 days before ESD, patients by performing a statistical analysis using Graph- and they discontinued cilostazol the day of ESD. All anti- Pad Prism (http://biostat.mc.vanderbilt.edu/wiki/Main/ platelet drugs were resumed the day after ESD. The three PowerSampleSize). endoscopists who performed ESD were members of the Japan Gastroenterological Endoscopy Society and received Devices a lecture on the DDSS beforehand. In the C group, a 50-mm square-shaped PGAs was Endoscopes: GIF TYPE XP260NS (Olympus Co., Tokyo, gripped by grasping forceps through an endoscopic channel Japan). and delivered from the mouth to the stomach along with Incisional knife: Dual knife®(KD-650  L), IT knife the endoscope. The PGAs coating time was defined as the 2®(KD-611L) (Olympus Co., Tokyo, Japan). duration from the beginning of endoscope insertion into the Incisional generator device: ERBE VIO300D (Elektro- mouth to the end of the fibrin glue coating process. medizin, Tübingen, Germany). In the DDSS group, a nasal endoscope with an attached CO insufflation device: OLYMPUS UCR (Olympus Co., DDSS was prepared beforehand following specified proce- Tokyo, Japan). dures. The PGAs coating time was defined the same as it was PGAs (Gunze Co., Kyoto, Japan). for the C group. In addition to several parameters measured during ESD, other calculations and analyses were conducted Procedures for using the PGAs DDSS (Videos 1 as follows: and 2) The short axis (S) and long axis (L) (cm) of the ellipsoid dissected specimen were measured after ESD. Video 1 The ellipsoid coating area was defined as the area calcu- An endoscopic injection sclerotherapy (EIS) balloon (MD- lated by the following formula: the ellipsoid coating area 47411L, 8 mm in diameter, 60 mm in length) (Sumitomo (cm ) = π × L/2 × S/2 (π = 3.14) Bakelite Co., Tokyo, Japan) and a nasal endoscope (GIF The coating area per minute was calculated by the follow- TYPE XP260NS, Olympus Co., Tokyo, Japan) were pre- ing formula: the coating area per minute (cm /min) = the pared. Ring-shaped threads 3–4 mm in diameter of different ellipsoid coating area (cm )/the PGAs coating time (min) colors were placed in each corner of the 50-mm PGAs. A 5-cm thread was attached to one side of the square PGAs and was used for housing PGAs in the EIS balloon (Fig. 2A). The nasal endoscope was inserted into the EIS balloon, and the Outcomes 5-cm thread attached on PGAs was pulled through the EIS balloon (Fig. 2B). PGAs was stored in the gap between the Primary outcome nasal endoscope and the EIS balloon (Fig. 2C). PGAs was 1. Coating area per minute in the C group and DDSS distributed equally around the nasal endoscope (Fig. 2D). group, respectively (cm /min). PGAs was equally distributed around the nasal endoscope (Fig. 3A, B). Approximately 4.5 ml of air was insufflated, which did not cause outer EIS balloon swelling (Fig. 3C). Secondary outcomes Thus completing the preparation of the nasal endoscope with PGAs delivery system (NE-PGAs) was made (Fig. 3D). 2. Post-ESD bleeding (1–7 days after ESD): post-ESD bleeding was defined as bleeding that required an inter - Video 2 vention with hemostatic forceps. 3. Post-ESD perforation (1–7 days after ESD). Esophagogastroduodenoscopy revealed rather thick, 0-IIa-type, early gastric cancer 45  mm in diameter in Sample size calculation the posterior wall of the body of the stomach (Fig. 4A). The post-ESD artificial ulcer became 50 mm in diame- After we conducted a pilot study of five patients in the C ter (Fig. 4B). NE-PGAs was inserted from the mouth to group and five patients in the DDSS group (a total of ten the stomach (Fig.  4C). After 4.5 ml of air was deflated patients), we found significant differences between the from the EIS balloon, the nasal endoscope was pulled two groups in the coating area per minute (C) (C and out through the EIS balloon (Fig. 4D). By pulling out the C) (cm /min). Based on these results, the sample size nasal endoscope slowly, PGAs was observed (Fig. 4E). By DDSS required for an α error of 0.05 and a power of 0.8 with a grasping the thread, PGAs could be pulled out from the standard deviation of 0.0351 was calculated to be 20 NE-PGAs (Fig. 4F). PGAs was brought to the post-ESD 1 3 Surgical Endoscopy (2018) 32:3076–3086 3079 Fig. 2 PGAs with ring-shaped threads of four different colors. A tors. For example, the thread on the contralateral side to the black A PGAs was cut into a 50-mm square sheet. Ring-shaped threads thread was green, and that to the white thread was purple. B A nasal 3–4  mm in diameter of four different colors were placed in the cor - endoscope was inserted into an endoscopic injection sclerotherapy ners of a 50-mm square sheet. A ring-shaped thread was also placed (EIS) balloon, and the 5-cm thread on one side of the square PGAs in the center of PGAs. The location of each colored thread is impor- was pulled through the EIS balloon. C PGAs was stored in the gap tant for recognizing the orientation of PGAs, especially if PGAs between the nasal endoscope and the EIS balloon by pulling the becomes wet and curled up in the stomach due to unpredicted fac- thread. D Then, PGAs was placed equally around the nasal endoscope ulcer (Fig.  5A). PGAs was unfolded by referencing the Results four threads attached to the corners (Fig. 5B). All of the threads attached to PGAs were clipped and fixed equally There were no significant differences in patient age or gender (Fig. 5C). More clips were added just above the ulcer floor (p = 0.66 and 0.848, respectively) between the C group and (Fig. 5D). Beriplast P Combi-Set Tissue Adhesive®(CSL DDSS group. Regarding the location of lesions, in the C Behring K.K., Tokyo, Japan) (combination of fibrin glue group (19 lesions), six were upper (U) lesions, seven were and thrombin) was applied equally to the artificial ulcer middle (M) lesions, and six were lower (L) lesions. In the (Fig. 5E). The tight attachment of PGAs to the post-ESD DDSS group (20 lesions), five were U lesions, eight were M artificial ulcer floor was completed (Fig.  5F). lesions, and seven were L lesions. There was no significant difference in lesion location (p = 0.209). The macroscopic findings of lesions revealed that the Statistical analysis 0-IIa, 0-IIc, and 0-IIa + IIc types accounted for 6, 4, and 9 lesions, respectively, in the C group. In the DDSS group, the For comparing the relative frequencies between groups, 0-IIa, 0-IIc, and 0-IIa + IIc types accounted for 7, 5, and 8 data were analyzed using Fisher’s exact test or the χ test. lesions, respectively. There was no significant difference in The Mann–Whitney U test was used to compare continu- the macroscopic findings (p = 0.479) (Table 1). ous variables with a significance level of p < 0.05. St a- There was also no significant difference in the ellipsoid 2 2 tistical analyses were performed using GraphPad Prism dissected area (cm ), with areas of 16.9 (3.68–25.3) cm version 5.00 for Windows (GraphPad Software, San Diego, and 15.3 (3.56–27.2) cm for the C group and DDSS group, CA, USA). respectively (p = 0.555) (Table 2) (Fig. 6A). There was a 1 3 3080 Surgical Endoscopy (2018) 32:3076–3086 Fig. 3 PGAs stored equally around the nasal endoscope by air insuf- PGAs was sealed between the endoscope and the inner bulge of the flation. A Using tweezers, PGAs was adjusted to be placed equally swollen balloon, then, insufflating approximately 4.5 ml of air did not around the nasal endoscope. B As viewed from in front of the endo- cause the outer balloon to swell and PGAs was sealed in the center of scope tip, the PGAS was placed in the gap between the EIS and nasal an EIS balloon. D Thus completing the preparation of the nasal endo- endoscope. C As EIS balloons swell equally outward and inward, scope with PGAs delivery system (NE-PGAs) was made significant difference in the coating time (min), with values after ESD) in the C group compared with 0 in the DDSS of 34.1 (15.0–60.7) and 16.85 (11.5–27.2) min for the C group, which was significantly different (p = 0.030). There group and DDSS group, respectively (p = 0.001) (Fig. 6B). were 0 cases of perforation during ESD in both groups, with In the coating areas per minute (cm /min), there was a sig- no significant difference (p = 0.725) (Table 2). Instances of nificant difference, with values of 0.261 (0.02–1.00) cm / post-ESD bleeding were successfully controlled with hemo- min and 0.96 (0.173–2.06) cm /min (p = 0.001) (Table 2) static forceps. Total seven patients in C groups and eight (Fig. 6C) for the C group and DDSS group, respectively. patients in DDSS groups allowed us to perform follow up Anticoagulants were used in four and five patients in the EGD examination. Patients those PGAs remained until post- C group and DDSS group, respectively (p = 0.777). Anti- operational day (POD) 3, 7, 14, 30, and 60 were 4/2/1/0/0 platelet drugs were used in three and four patients in the patients in C groups, and 1/2/5/0/0 patients in DDSS groups C group and DDSS group, respectively (p = 0.740). There with significant difference (p = 0.0006). The typical heal- were no signic fi ant die ff rences between the groups (Table  1). ing course of the PGAS-coated post-ESD ulcer floor in the Among antiplatelet drugs, aspirin/ticlopidine hydrochlo- DDSS group is shown in Fig. 7. Images were captured of ride/clopidogrel sulfate were taken by 2/3/2 patients in the C the PGAS-coated ulcer floor just after ESD (Fig.  7A) and group and by 3/4/2 patients in the DDSS group, respectively. on POD 3 (Fig. 7B), POD 7 (Fig. 7C), POD 14 (Fig. 7D), There was no significant difference in the use of antiplatelet POD 30 (Fig. 7E), and POD 60 (Fig. 7F). drugs between the groups (p = 0.383) (Table 1). There were Pathological examinations revealed no significant dif- 4 (21% of C group) cases of post-ESD bleeding (1–7 days ferences in early cancer invasion depth, i.e., mucosal, 1 3 Surgical Endoscopy (2018) 32:3076–3086 3081 Fig. 4 Procedures for delivering a PGAs using the DDSS. A Esoph- air was deflated from the EIS balloon and the nasal endoscope was agogastroduodenoscopy revealed rather thick 0-IIa-type early gastric pulled out through the EIS balloon with PGAs. E By pulling out cancer 45  mm in diameter in the posterior wall of the body of the the nasal endoscope slowly, the white and black threads attached to stomach. ESD was completed within 50 min with bleeding prevented PGAs corners could be observed. While the EIS balloon and PGAs by conducting pre-coagulation with coagulation forceps. B The post- remained in the stomach, the nasal endoscope was replaced by an oral ESD artificial ulcer became 50 mm in diameter. C A nasal endoscope endoscope to proceed with the treatment. F By grasping the thread with a PGAs (NE-PGAs) was inserted and passed from the mouth attached to the corner of PGAs, PGAs was pulled out from NE-PGAs to the stomach. D After placing NE-PGAs in the stomach, 4.5 ml of submucosal or sm massive, with 13, 4, and 2 cases in the approximately 3 months (15 weeks). Early anti-inflam- C group and 15, 3, and 2 cases in the DDSS group show- matory effects and rich granulation tissue formation not ing mucosal and submucosal invasion depths, respectively only prevent deformation of the post-ESD artificial ulcer (p = 0.593) (Table 2). by fibroblasts but also play a role in protecting the ulcer floor from exogenous materials and factors [11]. These protective mechanisms seem to be very similar to reactions Discussion induced by steroid local injection therapy to prevent steno- sis or deformation of the esophagus or stomach [12–14]. PGAs are made of PGA, which is widely used in bio- Although a PGAs has no inherent hemostatic activity, cov- absorbable sutures in the surgical field. During the heal- ering the ulcer floor with a PGAs and coating the covering ing process of a post-ESD artificial ulcer, a PGAs exerts with fibrin glue provide protection, deformity prevention, anti-inflammatory effects and prompts the creation of rich and hemostatic effects. The tight attachment of a PGAs to granulation tissue. Simultaneously, the PGAs prompts the artificial floor is necessary to obtain a sufficient hemo- the migration of epidermal cells over the rich granula- static effect; insufficient attachment leads to post-ESD tion tissue and accelerates the activity of fibroblasts to bleeding. PGAs is very useful for covering post-ESD ulcer form collagenous tissue with a scar. After these processes, floors to provide protection from exogenous materials and the PGAs becomes almost completely absorbed within hemostasis with an additional fibrin glue coating [15, 16]. 1 3 3082 Surgical Endoscopy (2018) 32:3076–3086 Fig. 5 Tight PGAs attachment. A PGAs was brought to the post- PGAs to the post-ESD artificial ulcer floor. D The periphery of PGAs artificial ulcer using forceps. B PGAs was unfolded by referencing was clipped and fixed equally just above the ulcer floor for tight the four threads attached to the corners and the one thread attached attachment. Finally, the red thread at the center of PGAs was fixed to the center of the PGAs (black thread: yellow arrow, white thread: at the center of the artificial ulcer. E Beriplast P Combi-Set Tissue white arrow, green thread: green arrow, purple thread: pink arrow, Adhesive®(combination of fibrin glue and thrombin) was applied red thread: blue arrow). C PGAs was clipped and fixed equally on equally to the artificial ulcer. F PGAs was completely and tightly each of the four corners by referring to the four colored threads, and attached to the post-ESD artificial ulcer floor clipping the center of PGAs was very important for tightly attaching Table 1 Baseline characteristics C group (n = 19) DDSS group (n = 20) p value* Age, years (median[range]) 76 [52–91] 77 [49–93] 0.66* Gender (male/female) 11/8 12/8 0.848** Locations of lesions 0.209**  U 6 5  M 7 8  L 6 7 Macroscopic findings of lesions 0.479***  0-IIa 6 7  0-IIc 4 5  0-IIa + IIc 9 8 Oral administration of antithrombotic agents  Anticoagulants 4 5 0.777*  Antiplatelets 3 4 0.740*  Aspirin/ticlopidine hydrochloride/clopidogrel sulfate 2/3/2 3/4/2 0.383**** *Unpaired t test, **χ test, ***Fisher’s exact test, ****non-repeated measures ANOVA test C group conventional PGAs delivery group, DDSS group PGAs delivery group using device delivery station system 1 3 Surgical Endoscopy (2018) 32:3076–3086 3083 Table 2 Results C group (n = 19) DDSS group (n = 20) p value* Ellipsoid dissected area (cm ), median (range) 16.9 (3.68–25.3) 15.3 (3.56–27.2) 0.555* Coating time (min), median (range) 34.1 (15.0–60.7) 16.85 (11.5–27.2) 0.001* Coating area per minute (cm /min), median (range) 0.261 (0.02–1.00) 0.96 (0.173–2.06) 0.001* Post-ESD bleeding (1–7 days after ESD) (cases) 4 (21%) 0 (0%) 0.030* Post-ESD perforation (1–7 days after ESD) (cases) 0 0 0.725* PGAs remained POD 3, 7, 14, 30, and 60 in ulcer floor 4/2/1/0/0 (Total 7 patients) 1/2/5/0/0 (Total 8 patients) 0.0006** Pathological invasion depth 0.593** M 13 15 Sm1 4 3 Sm massive 2 2 *Mann–Whitney U test, **Fisher’s exact test C group conventional PGAs delivery group, DDSS group PGAs delivery group using device delivery station system Fig. 6 Results. A There were no significant differences in the ellip- for the C and DDSS groups, respectively (p = 0.001). C There was a 2 2 soid dissected area (A) (cm ), with values of 16.9 (3.68–25.3) and significant difference in the coating area per minute (C) (cm /min), 2 2 15.3 (3.56–27.2) cm for the C and DDSS groups, respectively with values of 0.261 (0.02–1.00) and 0.96 (0.173–2.06) cm /min for (p = 0.555). B There were significant differences in the coating time the C and DDSS groups, respectively (p = 0.001) (T) (min), with values of 34.1 (15.0–60.7) and 16.85 (11.5–27.2) min On the other hand, there are two major problems in apply- and produced a prototype of the innovative device, i.e., ing a PGAs to a post-ESD ulcer floor, as follows: ① rapidly the E-DDSS (Fig. 8A). The E-DDSS can deliver various delivering the thin PGAs without exposing it to saliva or endoscopic devices that can be placed within the diges- gastric juice [10]; and ② tightly attaching the PGAs to the tive tract via a detachable functionality under completely ulcer floor using only a flexible endoscope such that a suf- sealed conditions (Fig. 8B). E-DDSS has two chambers ficient hemostatic effect is obtained [9 ]. For ①, we have in which PGAs were stored, and it was delivered by split- developed a novel endoscopic device delivery concept ting one side of the device by unlocked system (Fig. 8C). 1 3 3084 Surgical Endoscopy (2018) 32:3076–3086 Fig. 7 Typical healing course of the PGAs-coated post-ESD ulcer coated ulcer floor on POD 7. D The PGAs-coated ulcer floor on POD floor. A The PGAs-coated ulcer floor just after ESD. B The PGAs- 14. E The PGAs-coated ulcer floor on POD 30. F The PGAs-coated coated ulcer floor on post-operation day (POD) 3. C The PGAs- ulcer floor on POD 60 There were two types of E-DDSS prototypes (3 or 5 cm crucial events especially for patients who take antiplatelet in length) (Fig.  8D). From the E-DDSS attached to the agents. There were some reports that post-bleeding events endoscope, it is possible to pull out items loaded in the occurred within 7–14 days after ESD. Follow-up EGDs circumferential cavities, such as hemostatic gauze or a until POD 60 revealed PGAs remained on POD 7–14 in PGAs (Fig. 8E). The E-DDSS can be attached to an oral almost of all patients without post-ESD bleeding events. endoscope or a nasal endoscope (Fig. 8F). The E-DDSS Using a PGAs with four ring-shaped colored threads also is now being tested in several in vivo experiments. As a enabled the effective, tight attachment of the PGAS such DDSS that can deliver a PGAs is included within one of that post-ESD bleeding was decreased among patients the concepts of the E-DDSS, in this study, a DDSS that using antithrombotic agents [17–19]. In our study, with used an existing EIS balloon was used to deliver a PGAs, limitation of small number, although PGAs prevented and this approach yielded better results than the conven- post-ESD bleeding, it could not prevent the deformity of tional delivery method. However, using the DDSS with a post-ESD ulcer. Although there were several reports that nasal endoscope for PGAs delivery (NE-PGAs) required PGAs prevented stricture of esophagus after ESD [3, 11], the immediate replacement of the nasal endoscope by an we could not confirm anti-deformity effect of PGAs. Con- oral endoscope, which slightly increased the procedure sidering the healing process, PGAs prompts the migration duration [10]. For ②, tight PGAs attachment was achieved of epidermal cells and accelerates the activity of fibro- by using a PGAs with four ring-shaped colored threads blasts to form collagenous tissue with a scar, and these placed in the four corners of the sheet to more easily rec- effects might be able to prevent post-ESD bleeding, but ognize the orientation of the PGAs and facilitate sheet not deformity of stomach. Further multi-center studies are fixation with hemoclips. Post-ESD bleeding is one of the 1 3 Surgical Endoscopy (2018) 32:3076–3086 3085 Fig. 8 Concept and prototype of the endoscopic device delivery sta- condition. C E-DDSS has two chambers in which PGAs were stored, tion system (E-DDSS). A The E-DDSS can deliver various endo- and it was delivered by splitting one side of the device by unlocked scopic devices and place them within the digestive tract via a detach- system. D Two E-DDSS prototypes (3 or 5  cm in length). E From able functionality while maintaining completely sealed conditions. B independent E-DDSS attached to the endoscope, it is possible to E-DDSS can deliver various endoscopic devices and detained within pull out loaded items, such as hemostatic gauze or a PGAs. F The the digestive tract by detachable function under completely sealed E-DDSS can be attached to an oral endoscope or a nasal endoscope Open Access This article is distributed under the terms of the Creative needed to confirm the main effect of PGAs under the same Commons Attribution 4.0 International License (http://creativecom- coating method like DDSS. mons.org/licenses/by/4.0/), which permits unrestricted use, distribu- In conclusion, this DDSS was very useful for rapidly tion, and reproduction in any medium, provided you give appropriate delivering and tightly attaching a PGAs to control post- credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. ESD bleeding. Acknowledgements This research was (partially) supported by The Translational Research Program and the Strategic PRomotion for prac- References tical applications of INnovative medical Technology (TR-SPRINT) from the Japan Agency for Medical Research and Development 1. Maekawa S, Nomura R, Murase T, Ann Y, Harada M (2015) (AMED). Complete closure of artificial gastric ulcer after endoscopic sub- mucosal dissection by combined use of a single over-the-scope Author Contributions MH was responsible for conception and design; clip and through-the-scope clips (with videos). Surg Endosc GY, KH, KS, NN, KN analyzed and interpreted the data; MH and MT 29:500–504 drafted the article; MT criticized the revision of the article for impor- 2. Takimoto K, Toyonaga T, Matsuyama K (2012) Endoscopic tissue tant intellectual content; MT finally approved of the article. shielding to prevent delayed perforation associated with endo- scopic submucosal dissection for duodenal neoplasms. Endoscopy 44:E414–E415 Compliance with ethical standards 3. Sakaguchi Y, Tsuji Y, Ono S, Saito I, Kataoka Y, Takahashi Y, Nakayama C, Shichijo S, Matsuda R, Minatsuki C, Asada-Hiray- Conflict of interest Dr. Hirohito Mori was partially supported by ama I, Niimi K, Kodashima S, Yamamichi N, Fujishiro M, Koike the Japan Agency for Medical Research and Development (AMED). K. (2015) Polyglycolic acid sheets with fibrin glue can prevent Drs. Yu Guan, Hideki Kobara, Seiki Kobayashi, Noriko Nishiyama, esophageal stricture after endoscopic submucosal dissection. Nobuya Kobayashi, Tsutomu Masaki have no conflicts of interest or Endoscopy. 47:336–340 financial ties to disclose. 4. Doyama H, Tominaga K, Yoshida N, Takemura K, Yamada S (2014) Endoscopic tissue shielding with polyglycolic acid sheets, 1 3 3086 Surgical Endoscopy (2018) 32:3076–3086 fibrin glue and clips to prevent delayed perforation after duodenal 13. Hanaoka N, Ishihara R, Takeuchi Y, Uedo N, Higashino K, Ohta endoscopic resection. Dig Endosc 26(Suppl 2):41–45 T, Kanzaki H, Hanafusa M, Nagai K, Matsui F, Iishi H, Tatsuta 5. Takimoto K, Imai Y, Matsuyama K (2014) Endoscopic tissue M, Ito Y (2012) Intralesional steroid injection to prevent stricture shielding method with polyglycolic acid sheets and fibrin glue after endoscopic submucosal dissection for esophageal cancer: a to prevent delayed perforation after duodenal endoscopic submu- controlled prospective study. Endoscopy 44:1007–1011 cosal dissection. Dig Endosc 26(Suppl 2):46–49 14. Mori H, Rafiq K, Kobara H, Fujihara S, Nishiyama N, Kobayashi 6. Tsuji Y, Ohata K, Gunji T, Shozushima M, Hamanaka J, Ohno A, M, Himoto T, Haba R, Hagiike M, Izuishi K, Okano K, Suzuki Ito T, Yamamichi N, Fujishiro M, Matsuhashi N, Koike K (2014) Y, Masaki T (2012) Local steroid injection into the artificial ulcer Endoscopic tissue shielding method with polyglycolic acid sheets created by endoscopic submucosal dissection for gastric cancer: and fibrin glue to cover wounds after colorectal endoscopic sub- prevention of gastric deformity. Endoscopy 44:641–648 mucosal dissection (with video). Gastrointest Endosc 79:151–155 15. Tsuji Y, Fujishiro M, Kodashima S, Ono S, Niimi K, Mochizuki 7. Takao T, Takegawa Y, Shinya N, Tsudomi K, Oka S, Ono H S, Asada-Hirayama I, Matsuda R, Minatsuki C, Nakayama C, (2015) Tissue shielding with polyglycolic acid sheets and fibrin Takahashi Y, Sakaguchi Y, Yamamichi N, Koike K (2015) Poly- glue on ulcers induced by endoscopic submucosal dissection in a glycolic acid sheets and fibrin glue decrease the risk of bleeding porcine model. Endosc Int Open 3:E146–E151 after endoscopic submucosal dissection of gastric neoplasms (with 8. Ono H, Takizawa K, Kakushima N, Tanaka M, Kawata N (2015) video). Gastrointest Endosc 81:906–912 Application of polyglycolic acid sheets for delayed perforation 16. Ono S, Tsuji Y, Fujishiro M, Kodashima S, Yamamichi N, Koike after endoscopic submucosal dissection of early gastric cancer. K (2014) An effective technique for delivery of polyglycolic acid Endoscopy 47(Suppl 1 UCTN):E18–E19 sheet after endoscopic submucosal dissection of the esophagus: 9. Takao T, Takegawa Y, Ono H, Takao M, Oka S, Shinya N, Kut- the clip and pull method. Endoscopy 46(Suppl 1 UCTN):E44–E45 sumi H, Azuma T (2017) A novel and effective delivery method 17. Shindo Y, Matsumoto S, Miyatani H, Yoshida Y, Mashima H for polyglycolic acid sheets to post-endoscopic submucosal dis- (2016) Risk factors for postoperative bleeding after gastric endo- section ulcers. Endoscopy 49:359–364 scopic submucosal dissection in patients under antithrombotics. 10. Mori H, Kobara H, Rahman A, Nishiyama N, Nishiyama A, World J Gastrointest Endosc 8:349–356 Suzuki Y, Masaki T (2017) Innovative delivery method using a 18. Matsumura T, Arai M, Maruoka D, Okimoto K, Minemura S, detachable device to deliver a large polyglycolic acid sheet to a Ishigami H, Saito K, Nakagawa T, Katsuno T, Yokosuka O (2014) gastric ulcer perforation. Endoscopy 49(7):E165–E167 Risk factors for early and delayed post-operative bleeding after 11. Iizuka T, Kikuchi D, Yamada A, Hoteya S, Kajiyama Y, Kaise M endoscopic submucosal dissection of gastric neoplasms, includ- (2015) Polyglycolic acid sheet application to prevent esophageal ing patients with continued use of antithrombotic agents. BMC stricture after endoscopic submucosal dissection for esophageal Gastroenterol 14:172 squamous cell carcinoma. Endoscopy 47:341–344 19. Fukuda H, Yamaguchi N, Isomoto H, Matsushima K, Minami H, 12. Hashimoto S, Kobayashi M, Takeuchi M, Sato Y, Narisawa R, Akazawa Y, Ohnita K, Takeshima F, Shikuwa S, Nakao K (2016) Aoyagi Y (2011) The efficacy of endoscopic triamcinolone injec- Polyglycolic acid felt sealing method for prevention of bleeding tion for the prevention of esophageal stricture after endoscopic related to endoscopic submucosal dissection in patients taking submucosal dissection. Gastrointest Endosc 74:1389–1393 antithrombotic agents. Gastroenterol Res Pract 2016:1457357 1 3 http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Surgical Endoscopy Springer Journals

Efficacy of innovative polyglycolic acid sheet device delivery station system: a randomized prospective study

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Springer Journals
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Copyright © 2017 by The Author(s)
Subject
Medicine & Public Health; Surgery; Gynecology; Gastroenterology; Hepatology; Proctology; Abdominal Surgery
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0930-2794
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1432-2218
D.O.I.
10.1007/s00464-017-6019-6
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Abstract

Background Although there have been several reports of treating large post-endoscopic submucosal dissection (ESD) ulcers by covering them with a polyglycolic acid sheet (PGAs), this approach presents problems regarding PGAs delivery. This study assessed the usefulness of a device delivery station system (DDSS) to evaluate the appropriate and rapid PGAs coat- ing method with DDSS. Methods Thirty-nine of 41 patients who were diagnosed with early gastric cancer over 20 mm in diameter and pathologi- cally diagnosed with well-differentiated adenocarcinoma were randomly allocated to the following two groups according to delivery method: the conventional PGAs delivery group (C group) (n = 19) and the new DDSS group (DDSS group) (n = 20). The primary outcome was the coating area per minute in the C group and DDSS group (cm /min). Results There were significant differences in the coating time (min), with values of 34.1 (15.0–60.7) vs. 16.85 (11.5–27.2) min for the C group and DDSS group, respectively (p = 0.001). There was also a significant difference in coating area per minute, with values of 0.261 (0.02–1.00) and 0.96 (0.173–2.06) cm /min for the C group and DDSS group, respectively (p = 0.001). There were four cases of post-ESD bleeding (1–7 days after ESD) in the C group compared with 0 in the DDSS group, which represented a significant difference (p = 0.030). Conclusions The DDSS was very useful for rapidly delivering and tightly attaching a PGAs to control post-ESD bleeding. Trial registration University Hospital Medical Network (UMIN) 000026377. Keywords Delivery of polyglycolic acid sheet · Coating area per minute · Post-endoscopic submucosal dissection bleeding · Device delivery station system There have been several reports of treatments for large, an over-the-scope clip (OTSC) system (Ovesco Endoscopy artificial post-endoscopic submucosal dissection (ESD) GmbH, Tüebingen, Germany) [1] and covering an ulcer ulcers, such as natural ulcer healing, ulcer closure using with a polyglycolic acid sheet (PGAs) (Gunze Co., Kyoto, Japan); treatment with a PGAs has been used in particular to prevent post-ESD bleeding [2, 3]. Although mechanical Electronic supplementary material The online version of this means of closing larger and deeper mucosal defects via a article (https://doi.org/10.1007/s00464-017-6019-6) contains hemoclip or OTSC system, which reach deeper, submucosal supplementary material, which is available to authorized users. layers after ESD, effectively prevent post-ESD bleeding or * Hirohito Mori delayed perforation to some extent, such mechanical clo- hiro4884@med.kagawa-u.ac.jp sures create a mucosal bridge over the remaining muscu- lar layer when applied without a coating or covering for Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki, larger, deeper defects reaching submucosal layers. Filling Kita, Kagawa 761-0793, Japan and covering a large, deep defect with a PGAs is a more Department of Pharmacology, Kagawa University, 1750-1 natural and effective way for treating large post-ESD arti- Ikenobe, Miki, Kita, Kagawa 761-0793, Japan ficial ulcers to prevent post-ESD adverse events, such as Department of Gastroenterological Surgery, Ehime bleeding and perforation. It is especially difficult to close Rosai Hospital, 13-27, Minamikomatsubara, Niihama, artificial ulcers ≥ 5 cm using a hemoclip or OTSC closure. Ehime 792-8550, Japan Vol:.(1234567890) 1 3 Surgical Endoscopy (2018) 32:3076–3086 3077 As such, filling and covering large artificial defects with a Patients and methods PGAs is a more ideal treatment approach; however, it is dif- ficult to deliver and thoroughly cover an ulcer floor with This study was conducted with approval from the ethics a thin PGAs using only a pan-endoscope, especially under committees of the Ehime Rosai and Kagawa University wet conditions. PGAs delivery is one of the main problems Hospitals (Approval No. 80) and in accordance with the of treating artificial ulcers. The conventional PGAs coating Declaration of Helsinki. The patients provided verbal and method is very time consuming and causes maneuverability written informed consent. This trial was also registered difficulties [4 –8]. As a 30- to 40-mm square-shaped PGAs is with the University Hospital Medical Information Network gripped by grasping forceps through the endoscopic channel (UMIN000026377) following the CONSORT check list. and delivered from the mouth to the stomach along with the Forty-one patients who were diagnosed with early gastric endoscope, the PGAs is exposed to saliva and gastric juices, cancer over 20 mm in diameter by narrow band imaging and it is difficult for the PGAs to maintain its sheet shape magnified endoscopic examination (NBI-ME) and patho- under such wet conditions. Once a PGAs becomes curled up logically diagnosed with well-differentiated adenocarcinoma in the stomach, it is very difficult if not impossible to uncurl from biopsy specimens were eligible for this prospective the PGAs into its sheet form using an endoscope [9, 10]. randomized study. Two patients refused to participate and This study aimed to evaluate the efficacy of appropriate and were excluded. The remaining 39 patients were randomly rapid PGAs coating method using device delivery station allocated using the sealed envelope method into the follow- system (DDSS). ing two groups according to the delivery method: the con- ventional PGAs delivery group (n = 19) (C group) and the new DDSS group (n = 20) (DDSS group) (Fig. 1). Patients taking ticlopidine hydrochloride, clopidogrel sulfate or Fig. 1 Flow chart of this study 1 3 3078 Surgical Endoscopy (2018) 32:3076–3086 aspirin were switched to cilostazol 3 days before ESD, patients by performing a statistical analysis using Graph- and they discontinued cilostazol the day of ESD. All anti- Pad Prism (http://biostat.mc.vanderbilt.edu/wiki/Main/ platelet drugs were resumed the day after ESD. The three PowerSampleSize). endoscopists who performed ESD were members of the Japan Gastroenterological Endoscopy Society and received Devices a lecture on the DDSS beforehand. In the C group, a 50-mm square-shaped PGAs was Endoscopes: GIF TYPE XP260NS (Olympus Co., Tokyo, gripped by grasping forceps through an endoscopic channel Japan). and delivered from the mouth to the stomach along with Incisional knife: Dual knife®(KD-650  L), IT knife the endoscope. The PGAs coating time was defined as the 2®(KD-611L) (Olympus Co., Tokyo, Japan). duration from the beginning of endoscope insertion into the Incisional generator device: ERBE VIO300D (Elektro- mouth to the end of the fibrin glue coating process. medizin, Tübingen, Germany). In the DDSS group, a nasal endoscope with an attached CO insufflation device: OLYMPUS UCR (Olympus Co., DDSS was prepared beforehand following specified proce- Tokyo, Japan). dures. The PGAs coating time was defined the same as it was PGAs (Gunze Co., Kyoto, Japan). for the C group. In addition to several parameters measured during ESD, other calculations and analyses were conducted Procedures for using the PGAs DDSS (Videos 1 as follows: and 2) The short axis (S) and long axis (L) (cm) of the ellipsoid dissected specimen were measured after ESD. Video 1 The ellipsoid coating area was defined as the area calcu- An endoscopic injection sclerotherapy (EIS) balloon (MD- lated by the following formula: the ellipsoid coating area 47411L, 8 mm in diameter, 60 mm in length) (Sumitomo (cm ) = π × L/2 × S/2 (π = 3.14) Bakelite Co., Tokyo, Japan) and a nasal endoscope (GIF The coating area per minute was calculated by the follow- TYPE XP260NS, Olympus Co., Tokyo, Japan) were pre- ing formula: the coating area per minute (cm /min) = the pared. Ring-shaped threads 3–4 mm in diameter of different ellipsoid coating area (cm )/the PGAs coating time (min) colors were placed in each corner of the 50-mm PGAs. A 5-cm thread was attached to one side of the square PGAs and was used for housing PGAs in the EIS balloon (Fig. 2A). The nasal endoscope was inserted into the EIS balloon, and the Outcomes 5-cm thread attached on PGAs was pulled through the EIS balloon (Fig. 2B). PGAs was stored in the gap between the Primary outcome nasal endoscope and the EIS balloon (Fig. 2C). PGAs was 1. Coating area per minute in the C group and DDSS distributed equally around the nasal endoscope (Fig. 2D). group, respectively (cm /min). PGAs was equally distributed around the nasal endoscope (Fig. 3A, B). Approximately 4.5 ml of air was insufflated, which did not cause outer EIS balloon swelling (Fig. 3C). Secondary outcomes Thus completing the preparation of the nasal endoscope with PGAs delivery system (NE-PGAs) was made (Fig. 3D). 2. Post-ESD bleeding (1–7 days after ESD): post-ESD bleeding was defined as bleeding that required an inter - Video 2 vention with hemostatic forceps. 3. Post-ESD perforation (1–7 days after ESD). Esophagogastroduodenoscopy revealed rather thick, 0-IIa-type, early gastric cancer 45  mm in diameter in Sample size calculation the posterior wall of the body of the stomach (Fig. 4A). The post-ESD artificial ulcer became 50 mm in diame- After we conducted a pilot study of five patients in the C ter (Fig. 4B). NE-PGAs was inserted from the mouth to group and five patients in the DDSS group (a total of ten the stomach (Fig.  4C). After 4.5 ml of air was deflated patients), we found significant differences between the from the EIS balloon, the nasal endoscope was pulled two groups in the coating area per minute (C) (C and out through the EIS balloon (Fig. 4D). By pulling out the C) (cm /min). Based on these results, the sample size nasal endoscope slowly, PGAs was observed (Fig. 4E). By DDSS required for an α error of 0.05 and a power of 0.8 with a grasping the thread, PGAs could be pulled out from the standard deviation of 0.0351 was calculated to be 20 NE-PGAs (Fig. 4F). PGAs was brought to the post-ESD 1 3 Surgical Endoscopy (2018) 32:3076–3086 3079 Fig. 2 PGAs with ring-shaped threads of four different colors. A tors. For example, the thread on the contralateral side to the black A PGAs was cut into a 50-mm square sheet. Ring-shaped threads thread was green, and that to the white thread was purple. B A nasal 3–4  mm in diameter of four different colors were placed in the cor - endoscope was inserted into an endoscopic injection sclerotherapy ners of a 50-mm square sheet. A ring-shaped thread was also placed (EIS) balloon, and the 5-cm thread on one side of the square PGAs in the center of PGAs. The location of each colored thread is impor- was pulled through the EIS balloon. C PGAs was stored in the gap tant for recognizing the orientation of PGAs, especially if PGAs between the nasal endoscope and the EIS balloon by pulling the becomes wet and curled up in the stomach due to unpredicted fac- thread. D Then, PGAs was placed equally around the nasal endoscope ulcer (Fig.  5A). PGAs was unfolded by referencing the Results four threads attached to the corners (Fig. 5B). All of the threads attached to PGAs were clipped and fixed equally There were no significant differences in patient age or gender (Fig. 5C). More clips were added just above the ulcer floor (p = 0.66 and 0.848, respectively) between the C group and (Fig. 5D). Beriplast P Combi-Set Tissue Adhesive®(CSL DDSS group. Regarding the location of lesions, in the C Behring K.K., Tokyo, Japan) (combination of fibrin glue group (19 lesions), six were upper (U) lesions, seven were and thrombin) was applied equally to the artificial ulcer middle (M) lesions, and six were lower (L) lesions. In the (Fig. 5E). The tight attachment of PGAs to the post-ESD DDSS group (20 lesions), five were U lesions, eight were M artificial ulcer floor was completed (Fig.  5F). lesions, and seven were L lesions. There was no significant difference in lesion location (p = 0.209). The macroscopic findings of lesions revealed that the Statistical analysis 0-IIa, 0-IIc, and 0-IIa + IIc types accounted for 6, 4, and 9 lesions, respectively, in the C group. In the DDSS group, the For comparing the relative frequencies between groups, 0-IIa, 0-IIc, and 0-IIa + IIc types accounted for 7, 5, and 8 data were analyzed using Fisher’s exact test or the χ test. lesions, respectively. There was no significant difference in The Mann–Whitney U test was used to compare continu- the macroscopic findings (p = 0.479) (Table 1). ous variables with a significance level of p < 0.05. St a- There was also no significant difference in the ellipsoid 2 2 tistical analyses were performed using GraphPad Prism dissected area (cm ), with areas of 16.9 (3.68–25.3) cm version 5.00 for Windows (GraphPad Software, San Diego, and 15.3 (3.56–27.2) cm for the C group and DDSS group, CA, USA). respectively (p = 0.555) (Table 2) (Fig. 6A). There was a 1 3 3080 Surgical Endoscopy (2018) 32:3076–3086 Fig. 3 PGAs stored equally around the nasal endoscope by air insuf- PGAs was sealed between the endoscope and the inner bulge of the flation. A Using tweezers, PGAs was adjusted to be placed equally swollen balloon, then, insufflating approximately 4.5 ml of air did not around the nasal endoscope. B As viewed from in front of the endo- cause the outer balloon to swell and PGAs was sealed in the center of scope tip, the PGAS was placed in the gap between the EIS and nasal an EIS balloon. D Thus completing the preparation of the nasal endo- endoscope. C As EIS balloons swell equally outward and inward, scope with PGAs delivery system (NE-PGAs) was made significant difference in the coating time (min), with values after ESD) in the C group compared with 0 in the DDSS of 34.1 (15.0–60.7) and 16.85 (11.5–27.2) min for the C group, which was significantly different (p = 0.030). There group and DDSS group, respectively (p = 0.001) (Fig. 6B). were 0 cases of perforation during ESD in both groups, with In the coating areas per minute (cm /min), there was a sig- no significant difference (p = 0.725) (Table 2). Instances of nificant difference, with values of 0.261 (0.02–1.00) cm / post-ESD bleeding were successfully controlled with hemo- min and 0.96 (0.173–2.06) cm /min (p = 0.001) (Table 2) static forceps. Total seven patients in C groups and eight (Fig. 6C) for the C group and DDSS group, respectively. patients in DDSS groups allowed us to perform follow up Anticoagulants were used in four and five patients in the EGD examination. Patients those PGAs remained until post- C group and DDSS group, respectively (p = 0.777). Anti- operational day (POD) 3, 7, 14, 30, and 60 were 4/2/1/0/0 platelet drugs were used in three and four patients in the patients in C groups, and 1/2/5/0/0 patients in DDSS groups C group and DDSS group, respectively (p = 0.740). There with significant difference (p = 0.0006). The typical heal- were no signic fi ant die ff rences between the groups (Table  1). ing course of the PGAS-coated post-ESD ulcer floor in the Among antiplatelet drugs, aspirin/ticlopidine hydrochlo- DDSS group is shown in Fig. 7. Images were captured of ride/clopidogrel sulfate were taken by 2/3/2 patients in the C the PGAS-coated ulcer floor just after ESD (Fig.  7A) and group and by 3/4/2 patients in the DDSS group, respectively. on POD 3 (Fig. 7B), POD 7 (Fig. 7C), POD 14 (Fig. 7D), There was no significant difference in the use of antiplatelet POD 30 (Fig. 7E), and POD 60 (Fig. 7F). drugs between the groups (p = 0.383) (Table 1). There were Pathological examinations revealed no significant dif- 4 (21% of C group) cases of post-ESD bleeding (1–7 days ferences in early cancer invasion depth, i.e., mucosal, 1 3 Surgical Endoscopy (2018) 32:3076–3086 3081 Fig. 4 Procedures for delivering a PGAs using the DDSS. A Esoph- air was deflated from the EIS balloon and the nasal endoscope was agogastroduodenoscopy revealed rather thick 0-IIa-type early gastric pulled out through the EIS balloon with PGAs. E By pulling out cancer 45  mm in diameter in the posterior wall of the body of the the nasal endoscope slowly, the white and black threads attached to stomach. ESD was completed within 50 min with bleeding prevented PGAs corners could be observed. While the EIS balloon and PGAs by conducting pre-coagulation with coagulation forceps. B The post- remained in the stomach, the nasal endoscope was replaced by an oral ESD artificial ulcer became 50 mm in diameter. C A nasal endoscope endoscope to proceed with the treatment. F By grasping the thread with a PGAs (NE-PGAs) was inserted and passed from the mouth attached to the corner of PGAs, PGAs was pulled out from NE-PGAs to the stomach. D After placing NE-PGAs in the stomach, 4.5 ml of submucosal or sm massive, with 13, 4, and 2 cases in the approximately 3 months (15 weeks). Early anti-inflam- C group and 15, 3, and 2 cases in the DDSS group show- matory effects and rich granulation tissue formation not ing mucosal and submucosal invasion depths, respectively only prevent deformation of the post-ESD artificial ulcer (p = 0.593) (Table 2). by fibroblasts but also play a role in protecting the ulcer floor from exogenous materials and factors [11]. These protective mechanisms seem to be very similar to reactions Discussion induced by steroid local injection therapy to prevent steno- sis or deformation of the esophagus or stomach [12–14]. PGAs are made of PGA, which is widely used in bio- Although a PGAs has no inherent hemostatic activity, cov- absorbable sutures in the surgical field. During the heal- ering the ulcer floor with a PGAs and coating the covering ing process of a post-ESD artificial ulcer, a PGAs exerts with fibrin glue provide protection, deformity prevention, anti-inflammatory effects and prompts the creation of rich and hemostatic effects. The tight attachment of a PGAs to granulation tissue. Simultaneously, the PGAs prompts the artificial floor is necessary to obtain a sufficient hemo- the migration of epidermal cells over the rich granula- static effect; insufficient attachment leads to post-ESD tion tissue and accelerates the activity of fibroblasts to bleeding. PGAs is very useful for covering post-ESD ulcer form collagenous tissue with a scar. After these processes, floors to provide protection from exogenous materials and the PGAs becomes almost completely absorbed within hemostasis with an additional fibrin glue coating [15, 16]. 1 3 3082 Surgical Endoscopy (2018) 32:3076–3086 Fig. 5 Tight PGAs attachment. A PGAs was brought to the post- PGAs to the post-ESD artificial ulcer floor. D The periphery of PGAs artificial ulcer using forceps. B PGAs was unfolded by referencing was clipped and fixed equally just above the ulcer floor for tight the four threads attached to the corners and the one thread attached attachment. Finally, the red thread at the center of PGAs was fixed to the center of the PGAs (black thread: yellow arrow, white thread: at the center of the artificial ulcer. E Beriplast P Combi-Set Tissue white arrow, green thread: green arrow, purple thread: pink arrow, Adhesive®(combination of fibrin glue and thrombin) was applied red thread: blue arrow). C PGAs was clipped and fixed equally on equally to the artificial ulcer. F PGAs was completely and tightly each of the four corners by referring to the four colored threads, and attached to the post-ESD artificial ulcer floor clipping the center of PGAs was very important for tightly attaching Table 1 Baseline characteristics C group (n = 19) DDSS group (n = 20) p value* Age, years (median[range]) 76 [52–91] 77 [49–93] 0.66* Gender (male/female) 11/8 12/8 0.848** Locations of lesions 0.209**  U 6 5  M 7 8  L 6 7 Macroscopic findings of lesions 0.479***  0-IIa 6 7  0-IIc 4 5  0-IIa + IIc 9 8 Oral administration of antithrombotic agents  Anticoagulants 4 5 0.777*  Antiplatelets 3 4 0.740*  Aspirin/ticlopidine hydrochloride/clopidogrel sulfate 2/3/2 3/4/2 0.383**** *Unpaired t test, **χ test, ***Fisher’s exact test, ****non-repeated measures ANOVA test C group conventional PGAs delivery group, DDSS group PGAs delivery group using device delivery station system 1 3 Surgical Endoscopy (2018) 32:3076–3086 3083 Table 2 Results C group (n = 19) DDSS group (n = 20) p value* Ellipsoid dissected area (cm ), median (range) 16.9 (3.68–25.3) 15.3 (3.56–27.2) 0.555* Coating time (min), median (range) 34.1 (15.0–60.7) 16.85 (11.5–27.2) 0.001* Coating area per minute (cm /min), median (range) 0.261 (0.02–1.00) 0.96 (0.173–2.06) 0.001* Post-ESD bleeding (1–7 days after ESD) (cases) 4 (21%) 0 (0%) 0.030* Post-ESD perforation (1–7 days after ESD) (cases) 0 0 0.725* PGAs remained POD 3, 7, 14, 30, and 60 in ulcer floor 4/2/1/0/0 (Total 7 patients) 1/2/5/0/0 (Total 8 patients) 0.0006** Pathological invasion depth 0.593** M 13 15 Sm1 4 3 Sm massive 2 2 *Mann–Whitney U test, **Fisher’s exact test C group conventional PGAs delivery group, DDSS group PGAs delivery group using device delivery station system Fig. 6 Results. A There were no significant differences in the ellip- for the C and DDSS groups, respectively (p = 0.001). C There was a 2 2 soid dissected area (A) (cm ), with values of 16.9 (3.68–25.3) and significant difference in the coating area per minute (C) (cm /min), 2 2 15.3 (3.56–27.2) cm for the C and DDSS groups, respectively with values of 0.261 (0.02–1.00) and 0.96 (0.173–2.06) cm /min for (p = 0.555). B There were significant differences in the coating time the C and DDSS groups, respectively (p = 0.001) (T) (min), with values of 34.1 (15.0–60.7) and 16.85 (11.5–27.2) min On the other hand, there are two major problems in apply- and produced a prototype of the innovative device, i.e., ing a PGAs to a post-ESD ulcer floor, as follows: ① rapidly the E-DDSS (Fig. 8A). The E-DDSS can deliver various delivering the thin PGAs without exposing it to saliva or endoscopic devices that can be placed within the diges- gastric juice [10]; and ② tightly attaching the PGAs to the tive tract via a detachable functionality under completely ulcer floor using only a flexible endoscope such that a suf- sealed conditions (Fig. 8B). E-DDSS has two chambers ficient hemostatic effect is obtained [9 ]. For ①, we have in which PGAs were stored, and it was delivered by split- developed a novel endoscopic device delivery concept ting one side of the device by unlocked system (Fig. 8C). 1 3 3084 Surgical Endoscopy (2018) 32:3076–3086 Fig. 7 Typical healing course of the PGAs-coated post-ESD ulcer coated ulcer floor on POD 7. D The PGAs-coated ulcer floor on POD floor. A The PGAs-coated ulcer floor just after ESD. B The PGAs- 14. E The PGAs-coated ulcer floor on POD 30. F The PGAs-coated coated ulcer floor on post-operation day (POD) 3. C The PGAs- ulcer floor on POD 60 There were two types of E-DDSS prototypes (3 or 5 cm crucial events especially for patients who take antiplatelet in length) (Fig.  8D). From the E-DDSS attached to the agents. There were some reports that post-bleeding events endoscope, it is possible to pull out items loaded in the occurred within 7–14 days after ESD. Follow-up EGDs circumferential cavities, such as hemostatic gauze or a until POD 60 revealed PGAs remained on POD 7–14 in PGAs (Fig. 8E). The E-DDSS can be attached to an oral almost of all patients without post-ESD bleeding events. endoscope or a nasal endoscope (Fig. 8F). The E-DDSS Using a PGAs with four ring-shaped colored threads also is now being tested in several in vivo experiments. As a enabled the effective, tight attachment of the PGAS such DDSS that can deliver a PGAs is included within one of that post-ESD bleeding was decreased among patients the concepts of the E-DDSS, in this study, a DDSS that using antithrombotic agents [17–19]. In our study, with used an existing EIS balloon was used to deliver a PGAs, limitation of small number, although PGAs prevented and this approach yielded better results than the conven- post-ESD bleeding, it could not prevent the deformity of tional delivery method. However, using the DDSS with a post-ESD ulcer. Although there were several reports that nasal endoscope for PGAs delivery (NE-PGAs) required PGAs prevented stricture of esophagus after ESD [3, 11], the immediate replacement of the nasal endoscope by an we could not confirm anti-deformity effect of PGAs. Con- oral endoscope, which slightly increased the procedure sidering the healing process, PGAs prompts the migration duration [10]. For ②, tight PGAs attachment was achieved of epidermal cells and accelerates the activity of fibro- by using a PGAs with four ring-shaped colored threads blasts to form collagenous tissue with a scar, and these placed in the four corners of the sheet to more easily rec- effects might be able to prevent post-ESD bleeding, but ognize the orientation of the PGAs and facilitate sheet not deformity of stomach. Further multi-center studies are fixation with hemoclips. Post-ESD bleeding is one of the 1 3 Surgical Endoscopy (2018) 32:3076–3086 3085 Fig. 8 Concept and prototype of the endoscopic device delivery sta- condition. C E-DDSS has two chambers in which PGAs were stored, tion system (E-DDSS). A The E-DDSS can deliver various endo- and it was delivered by splitting one side of the device by unlocked scopic devices and place them within the digestive tract via a detach- system. D Two E-DDSS prototypes (3 or 5  cm in length). E From able functionality while maintaining completely sealed conditions. B independent E-DDSS attached to the endoscope, it is possible to E-DDSS can deliver various endoscopic devices and detained within pull out loaded items, such as hemostatic gauze or a PGAs. F The the digestive tract by detachable function under completely sealed E-DDSS can be attached to an oral endoscope or a nasal endoscope Open Access This article is distributed under the terms of the Creative needed to confirm the main effect of PGAs under the same Commons Attribution 4.0 International License (http://creativecom- coating method like DDSS. mons.org/licenses/by/4.0/), which permits unrestricted use, distribu- In conclusion, this DDSS was very useful for rapidly tion, and reproduction in any medium, provided you give appropriate delivering and tightly attaching a PGAs to control post- credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. ESD bleeding. Acknowledgements This research was (partially) supported by The Translational Research Program and the Strategic PRomotion for prac- References tical applications of INnovative medical Technology (TR-SPRINT) from the Japan Agency for Medical Research and Development 1. Maekawa S, Nomura R, Murase T, Ann Y, Harada M (2015) (AMED). Complete closure of artificial gastric ulcer after endoscopic sub- mucosal dissection by combined use of a single over-the-scope Author Contributions MH was responsible for conception and design; clip and through-the-scope clips (with videos). Surg Endosc GY, KH, KS, NN, KN analyzed and interpreted the data; MH and MT 29:500–504 drafted the article; MT criticized the revision of the article for impor- 2. Takimoto K, Toyonaga T, Matsuyama K (2012) Endoscopic tissue tant intellectual content; MT finally approved of the article. shielding to prevent delayed perforation associated with endo- scopic submucosal dissection for duodenal neoplasms. Endoscopy 44:E414–E415 Compliance with ethical standards 3. Sakaguchi Y, Tsuji Y, Ono S, Saito I, Kataoka Y, Takahashi Y, Nakayama C, Shichijo S, Matsuda R, Minatsuki C, Asada-Hiray- Conflict of interest Dr. Hirohito Mori was partially supported by ama I, Niimi K, Kodashima S, Yamamichi N, Fujishiro M, Koike the Japan Agency for Medical Research and Development (AMED). K. (2015) Polyglycolic acid sheets with fibrin glue can prevent Drs. Yu Guan, Hideki Kobara, Seiki Kobayashi, Noriko Nishiyama, esophageal stricture after endoscopic submucosal dissection. Nobuya Kobayashi, Tsutomu Masaki have no conflicts of interest or Endoscopy. 47:336–340 financial ties to disclose. 4. Doyama H, Tominaga K, Yoshida N, Takemura K, Yamada S (2014) Endoscopic tissue shielding with polyglycolic acid sheets, 1 3 3086 Surgical Endoscopy (2018) 32:3076–3086 fibrin glue and clips to prevent delayed perforation after duodenal 13. Hanaoka N, Ishihara R, Takeuchi Y, Uedo N, Higashino K, Ohta endoscopic resection. Dig Endosc 26(Suppl 2):41–45 T, Kanzaki H, Hanafusa M, Nagai K, Matsui F, Iishi H, Tatsuta 5. Takimoto K, Imai Y, Matsuyama K (2014) Endoscopic tissue M, Ito Y (2012) Intralesional steroid injection to prevent stricture shielding method with polyglycolic acid sheets and fibrin glue after endoscopic submucosal dissection for esophageal cancer: a to prevent delayed perforation after duodenal endoscopic submu- controlled prospective study. Endoscopy 44:1007–1011 cosal dissection. Dig Endosc 26(Suppl 2):46–49 14. Mori H, Rafiq K, Kobara H, Fujihara S, Nishiyama N, Kobayashi 6. Tsuji Y, Ohata K, Gunji T, Shozushima M, Hamanaka J, Ohno A, M, Himoto T, Haba R, Hagiike M, Izuishi K, Okano K, Suzuki Ito T, Yamamichi N, Fujishiro M, Matsuhashi N, Koike K (2014) Y, Masaki T (2012) Local steroid injection into the artificial ulcer Endoscopic tissue shielding method with polyglycolic acid sheets created by endoscopic submucosal dissection for gastric cancer: and fibrin glue to cover wounds after colorectal endoscopic sub- prevention of gastric deformity. Endoscopy 44:641–648 mucosal dissection (with video). Gastrointest Endosc 79:151–155 15. Tsuji Y, Fujishiro M, Kodashima S, Ono S, Niimi K, Mochizuki 7. Takao T, Takegawa Y, Shinya N, Tsudomi K, Oka S, Ono H S, Asada-Hirayama I, Matsuda R, Minatsuki C, Nakayama C, (2015) Tissue shielding with polyglycolic acid sheets and fibrin Takahashi Y, Sakaguchi Y, Yamamichi N, Koike K (2015) Poly- glue on ulcers induced by endoscopic submucosal dissection in a glycolic acid sheets and fibrin glue decrease the risk of bleeding porcine model. Endosc Int Open 3:E146–E151 after endoscopic submucosal dissection of gastric neoplasms (with 8. Ono H, Takizawa K, Kakushima N, Tanaka M, Kawata N (2015) video). Gastrointest Endosc 81:906–912 Application of polyglycolic acid sheets for delayed perforation 16. Ono S, Tsuji Y, Fujishiro M, Kodashima S, Yamamichi N, Koike after endoscopic submucosal dissection of early gastric cancer. K (2014) An effective technique for delivery of polyglycolic acid Endoscopy 47(Suppl 1 UCTN):E18–E19 sheet after endoscopic submucosal dissection of the esophagus: 9. Takao T, Takegawa Y, Ono H, Takao M, Oka S, Shinya N, Kut- the clip and pull method. Endoscopy 46(Suppl 1 UCTN):E44–E45 sumi H, Azuma T (2017) A novel and effective delivery method 17. Shindo Y, Matsumoto S, Miyatani H, Yoshida Y, Mashima H for polyglycolic acid sheets to post-endoscopic submucosal dis- (2016) Risk factors for postoperative bleeding after gastric endo- section ulcers. Endoscopy 49:359–364 scopic submucosal dissection in patients under antithrombotics. 10. Mori H, Kobara H, Rahman A, Nishiyama N, Nishiyama A, World J Gastrointest Endosc 8:349–356 Suzuki Y, Masaki T (2017) Innovative delivery method using a 18. Matsumura T, Arai M, Maruoka D, Okimoto K, Minemura S, detachable device to deliver a large polyglycolic acid sheet to a Ishigami H, Saito K, Nakagawa T, Katsuno T, Yokosuka O (2014) gastric ulcer perforation. Endoscopy 49(7):E165–E167 Risk factors for early and delayed post-operative bleeding after 11. Iizuka T, Kikuchi D, Yamada A, Hoteya S, Kajiyama Y, Kaise M endoscopic submucosal dissection of gastric neoplasms, includ- (2015) Polyglycolic acid sheet application to prevent esophageal ing patients with continued use of antithrombotic agents. BMC stricture after endoscopic submucosal dissection for esophageal Gastroenterol 14:172 squamous cell carcinoma. Endoscopy 47:341–344 19. Fukuda H, Yamaguchi N, Isomoto H, Matsushima K, Minami H, 12. Hashimoto S, Kobayashi M, Takeuchi M, Sato Y, Narisawa R, Akazawa Y, Ohnita K, Takeshima F, Shikuwa S, Nakao K (2016) Aoyagi Y (2011) The efficacy of endoscopic triamcinolone injec- Polyglycolic acid felt sealing method for prevention of bleeding tion for the prevention of esophageal stricture after endoscopic related to endoscopic submucosal dissection in patients taking submucosal dissection. Gastrointest Endosc 74:1389–1393 antithrombotic agents. Gastroenterol Res Pract 2016:1457357 1 3

Journal

Surgical EndoscopySpringer Journals

Published: Jan 8, 2018

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