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Cold snare polypectomy reduced delayed postpolypectomy bleeding compared with conventional hot polypectomy: a propensity score-matching analysis

Cold snare polypectomy reduced delayed postpolypectomy bleeding compared with conventional hot... Original article Cold snare polypectomy reduced delayed postpolypectomy bleeding compared with conventional hot polypectomy: a propensity score-matching analysis Authors Takeshi Yamashina, Manabu Fukuhara, Takanori Maruo, Gensho Tanke, Saiko Marui, Ryota Sada, Mio Taki, Yoshiaki Ohara, Azusa Sakamoto, Shinichiro Henmi, Yugo Sawai, Sumio Saito, Norihiro Nishijima, Akihiro Nasu, Hideyuki Komekado, Akira Sekikawa, Masanori Asada, Takehiko Tumura, Ryuichi Kita, Toru Kimura, Yukio Osaki Institution DPPB after CSP and compare it with that of HP. A propensity Department of Gastroenterology and Hepatology, Osaka score model was used as a secondary analysis. Red Cross Hospital, Osaka, Japan Patients and methods This was a retrospective cohort study conducted in a single municipal hospital. We identi- submitted 21.8.2016 fied 539 patients with colorectal polyps from 2 mm to 11 accepted after revision 10.2.2017 mm in size who underwent CSP (804 polyps in 330 patients) or HP (530 polyps in 209 patients) between July 2013 and Bibliography June 2015. DOI https://doi.org/10.1055/s-0043-105578 | Results There were no cases of DPPB in the CSP group. Endoscopy International Open 2017; 05: E587–E594 Conversely, DPPB occurred in 4 patients (1.9 %) after HP, re- © Georg Thieme Verlag KG Stuttgart · New York sulting in a significant difference between the CSP and HP ISSN 2364-3722 groups (0.008 % vs 0 %, P = 0.02). Propensity score-match- ing analysis created 402 matched pairs, yielding a signifi- Corresponding author cantly higher DPPB rate in the HP group than CSP group Takeshi Yamashin, Department of Gastroenterology and (0.02 % vs 0 %, P = 0.04). However, significantly more pa- Hepatology, Osaka Red Cross Hospital, Osaka, Japan, tients in the CSP group had unclear horizontal margins 30 Fudegasaki, Tenouji, Osaka 543-8555, Japan that precluded assessment (83 vs 38 cases, P < 0.001). The Fax: (+81) 6-(6774)-5131 retrieval failure rate was significantly higher in the CSP [email protected] group than in the HP group (3 % vs 0.7 %, P = 0.01). Conclusions DPPB waslessfrequent withCSP than HP,as ABSTRACT selected by the propensity score-matching model. Our findings indicate that CSP is recommended polypectomy in Background and study aims Cold snare polypectomy daily clinical setting. However, special care should be taken (CSP) for small colorectal polyps has lower incidence of ad- during polyp retrieval and horizontal margin assessment, verse events, especially delayed postpolypectomy bleeding and these issues could be taken into account in follow-up (DPPB). However, few data are available on comparisons of after CSP. the incidence of DPPB of CSP and hot polypectomy (HP). The aim of this study was to evaluate the incidence of with electrocautery to remove colorectal polyps. However, Introduction two major adverse events (AEs), delayed post-polypectomy Colorectal carcinoma (CRC) is the fourth-most-common cause bleeding (DPPB) and perforation have remained an issue. In of cancer-related mortality worldwide [1] , and it is the third- previous reports, the incidence of DPPB of HP was 0.6 % to 2 % most-common cancer, with nearly 1.4 million new cases in [5 – 10]. Moreover, polyp size, shape, and location are risk fac- 2012 [2] . Most cases originate from adenomas [3] and their re- tors for DPPB [6, 10]. moval reduces the risk of death from CRC [4]. Therefore, if ade- In contrast, as far back as 20 years ago, cold snare polypec- nomas and cancers are detected early in their development, tomy (CSP) for small colorectal polyps has been reported to be they can be cured by endoscopic therapy. a safe and effective polyp removal method without electrocau- Hot polypectomy (HP), including hot snare polypectomy, tery [11 – 13]. This method is also superior to conventional po- endoscopic mucosal resection (EMR) and hot biopsy polypecto- lypectomy in terms of procedure time [14]. Thus, currently, CSP my, are the most commonly performed endoscopic therapies has gained notoriety. Moreover, the incidence of DPPB was re- Yamashina Takeshi et al. Cold snare polypectomy … Endoscopy International Open 2017; 05: E587–E594 E587 This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited. Original article ported to be 0 % to 1.8 % for CSP in previous prospective studies ways supervised the procedure in introduction period. The [15 –19], whichtends to be lower thanthat ofHP eveninpa- polyp was snared, including normal surrounding mucosa and tients that continued to receive anticoagulant treatment [17]. the snare was closed for transection of the polyp without elec- However, a previous study included only a small number of pa- trocautery. HP was performed with a similar type of videoendo- tients, and few studies have compared the incidence of DPPB of scope used for polypoid lesions. The same colonoscopists that CSP and HP in daily clinical setting. performed CSP mainly used the XEMEX Bipolar Snare S DRAGO- Randomized controlled trials are the most effective way of NARE™ (Xemex, Tokyo, Japan) to perform HP. As for EMR, nor- scientifically testing new medical interventions. However, the mal saline is injected into the submucosa before excision. The rate of DPPB is relatively low, and many cases are needed to Intelligent Cut and Coagulation 200 (ERBE Elektromedizin, Tü- conduct randomized controlled trials. Paspatis et al. conducted bingen, Germany) or VIO 300 D (ERBE) was used as a power a randomized controlled trial comparing CSP with hot snare HP source for electrical bipolar cutting and bipolar coagulation, in the occurrence of DPPB [19]. However, they didn’tstratify by and all participant endoscopists used the same setting. Before polyp size, and in it was significantly larger in the HP group than February 2014, we conventionally underwent clipping in most the CSP group and there was no DPPB in either group. Recently, HP cases. From that time onwards, the mucosal defects after propensity score matching has become a popular alternative to CSP or HP were large or if blood was spurting immediately, the randomized controlled trials [20]. We therefore hypothesized mucosal defect was closed using endoscopic clips. Usually, CSP that it would be more effective to use propensity score match- was performed as an outpatient procedure. And as many other ing analysis to compare CSP directly with HP. The aim of this Japanese hospitals, HP usually required a two-day hospitaliza- study was to evaluate the incidence of DPPB after colorectal tion. In general, most of Japanese patients who undergo poly- CSP and compare it with that after HP. Additionally, we per- pectomy or EMR are hospitalized for a few days. All patients un- formed secondary analysis with a propensity score model. derwent postoperative follow-up hospital visits about two weeks after polypectomy. Patients and methods Propensity score matching analysis Patients To reduce the possibility of selection bias and to identify control This retrospective cohort study was performed in a single mu- subjects, we performed propensity score matching with a ratio nicipal hospital. We identified consecutive patients with colo- of 1:1 and nearest neighbor matching without replacement rectal polyps from 2 mm to 11 mm in size who underwent CSP within a caliper width of 0.02 and the polyps for which the pro- or HP between July 2013 and June 2015 in our prospectively pensity score could not be matched because of a greater caliper maintained database of Osaka Red Cross Hospital, and enrolled distance were excluded from further analysis. To estimate the them into this analysis. Before February 2014, we mainly per- propensity score, we used a logistic regression model. Factors formed HP and after February 2014, we mainly performed CSP. related to DPPB have been previously reported to be polyp si- Patients with colorectal polyps larger than 5 mm who were re- zes, polyps located in the right-sided colon and polyp shape commended to undergo polypectomy and all polyps resected [6, 10]. Hence, variables included in the propensity score model endoscopically during screening colonoscopies were included were polyp size, polyp location (right-sided colon vs left-sided in the study. Patients who underwent colorectal HP and CSP colon) and polyp shape (Ip and Isp vs Is and IIa). procedures during operation or patients with perforation dur- Data analysis and definition of outcomes ing the procedure were excluded. This manuscript was prepar- ed accordingto the Strengtheningthe ReportingofObserva- The procedural details were recorded prospectively in a data- tional Studies in Epidemiology (STROBE) Statement [21]. base and their medical records were thoroughly investigated. The collected data included patient age, gender (male or fe- Endoscopic procedure and perioperative male), location (cecum, ascending colon, transverse colon, des- management cending colon, sigmoid colon, or rectum), tumor size, morpho- CSP or HP was performed under intravenous sedation with mid- logical type, and histological type (adenoma or serrated le- azolam. During colonoscope withdrawal, polyp location was sions, or carcinoma). The characteristics of lesions in the CSP documented and size was measured using biopsy forceps with group were compared with those in the HP group. Primary end- a 2.2-mm outer diameter or snares with an outer diameter of point of this study was DPPB rate after colorectal CSP and com- 11 mm to 20 mm. The phenotypes of polyps were classified ac- pare it with that after HP. Other AEs, retrieval failure rate and cording to the Paris classification [22]. Before polypectomy, horizontal margin were evaluated as secondary endpoints. chromoendoscopy or magnifying endoscopy was performed to DPPB was defined as hemochezia occurring > 24 hours after exclude the non-neoplastic lesions. The CSP was performed colorectal polypectomy that required an endoscopic hemostat- with a videoendoscope (CF-HQ290, PCF-PQ260 L, Olympus ic procedure. Medical Systems, Tokyo, Japan) for small (≤ 11 mm) polypoid le- Statistical analysis sions using Profile™ Polypectomy Snares (Boston Scientific Ja- pan, Tokyo, Japan) by 15 experienced colonoscopists who have The Fisher’sexact test or χ test was used for analysis of catego- sufficient expertise and experience of colorectal polypectomy. rical data. Quantitative data were compared using the Stu- They all thoroughly experienced CSP or otherwise specialists al- dent’s t test or Mann-Whitney U test. P<0.05 (two-sided) was Yamashina Takeshi et al. Cold snare polypectomy … Endoscopy International Open 2017; 05: E587–E594 E588 This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited. botic agents: aspirin; 8, clopidogrel; 3, cilostazol; 2, aspirin-dia- luminate;1,sarpogrelate; 1, limaprost alfadex; 1, apixaban; 1, 765 patients with colorectal polyp treated between July 2013 and June 2015 rivaroxaban; 1. Conversely in total 530 polyps in 209 patients were included in our analysis of HP group (Polypectomy: 329, Excluded EMR: 181, Hot biopsy: 20), and the baseline characteristics are ▪ polyps >11 mm n = 194 ▪ underwent HP and CSP presented in Table 1. Patients comprised 142 men and 69 n = 27 womenwithamedian age(range) of 66 (30 – 91) years. The ▪ With two antithrombotic agents n = 2 median resected tumor size (range) was 5 (2 – 11) mm, and ▪ No meticulous operative the lesions were located in the cecum, ascending colon, trans- record n = 3 verse colon, descending colon, sigmoid colon, and rectum in 28, 105, 123, 57, 169, and 49 cases, respectively. In the HP CSP n = 330 HP n = 209 group, eight patients discontinued the antithrombotic therapy and none of the patients continued the antithrombotic therapy. No differences were observed in gender, age, location or mor- ▶ Fig. 1 Flow diagram. CSP, cold snare polypectomy; HP, hot poly- phology between the CSP and HP groups (▶Table 2). pectomy Procedure-related outcomes In this study, therewerenocases of DPPB in theCSP group. considered significant. All statistical analyses were carried out Otherwise, although two cases were used clips for closure of using SPSS statistics version 23 (SPSS, Chicago, IL, USA). the mucosal defect, DPPB occurred in four patients (1.9 %) who underwent HP in different colonoscopists for colorectal polyps, resulting in a significant difference between the CSP Results and HP groups (0.008 % vs 0 %, P = 0.02). However, the HP group Baseline data had a significantly larger median resected polyp size (4 mm vs During the study period, 765 patients with colorectal polyps 5 mm, P = 0.01). There was no statistically significant differ- were treated by CSP or HP at the Osaka Red Cross Hospital dur- ence in histological type of polyp or assessment of the hori- ing the study period. A total of 226 patients were excluded zontal margin between the groups. The HP group had a signif- from the analysis because they had polyps > 11 mm (n = 194), icantly larger number of clips used for closure of the mucosal underwent another colorectal HP at the same time (n = 27), defect or hemoclip (79 % vs 6 %, P < 0.001). The retrieval failure continued treatment with two antithrombotic agents (n = 2) or rate was significantly higher in the CSP group than in the HP had no meticulous operative record (n = 3). A flow diagram of group (4 % vs 1 %, P = 0.001). All DPPB cases were managed the participants is shown in Fig. 1. In total, 804 polyps in 330 conservatively with the endoscopic hemostatic procedure and patients were included in our analysis of CSP group, and the no other serious AEs, such as perforation or postpolypectomy baseline characteristics are presented in ▶Table 1.Patients syndrome, were observed in either group. comprised 196 men and 134 women with a median age (range) Procedure-related outcomes after propensity score of 68 (27 – 91) years. The median resected tumor size (range) matching was 4 (2 – 11) mm, and the lesions were located in the cecum, ascending colon, transverse colon, descending colon, sigmoid The matching factors and treatment outcomes between the colon, and rectum in 50, 197, 203, 82, 206, and 66 cases, CSP and HP groups after propensity score matching are shown respectively (▶Table 2). Eighteen patients received antithrom- in ▶Table 3. Four hundred and two pairs were matched. Ten Table 1 Baseline characteristics of patients (n = 539). CSP group HP group P value Patients 330 209 0.07 ▪ Male (%) 196 (59 %) 142 (68 %) ▪ Female (%) 134 (41 % 69 (32 %) Median age (range, years) 68 (27 – 91) 66 (30 – 91) 1.0 Antithrombotic therapy < 0.001 ▪ None or discontinuation 312 209 ▪ Continuation 18 0 CSP, cold snare polypectomy; HP, hot snare polypectomy 1 2 χ test Student’s t test. Yamashina Takeshi et al. Cold snare polypectomy … Endoscopy International Open 2017; 05: E587–E594 E589 This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited. Original article Table 2 Baseline characteristics of lesions. CSP group HP group P value (n = 804) (n = 530) Location 0.3 ▪ Cecum 50 (6 %) 28 (5 %) ▪ Ascending colon 197 (25 %) 105 (20 %) ▪ Transverse colon 203 (25 %) 122 (23 %) ▪ Descending colon 82 (10 %) 57 (11 %) ▪ Sigmoid colon 206 (26 %) 169 (32 %) ▪ Rectum 66 (8 %) 49 (9 %) Morphology 0.6 ▪ Pedunculated type 16 (2 %) 24 (5 %) ▪ Semipedunculated type 130 (16 %) 132 (25 %) ▪ Sessile type 548 (68%) 239 (45%) ▪ Superficial elevated type 110 (14 %) 130 (25 %) ▪ Superficial depressed type 0 2 (0.4 %) ▪ Submucosal tumor 0 3 (0.6 %) Median tumor size (range, mm) 4 (2 – 11) 5 (2 – 11) 0.01 Histological type 0.1 ▪ Adenocarcinoma 0 (0 %) 12 (2 %) ▪ Adenoma 685 (85 %) 445 (84 %) ▪ Hyperplastic polyp 52 (6 %) 37 (7 %) ▪ Sessile serrated adenoma polyp 11 (1 %) 11 (2 %) ▪ Traditional serrated polyp 2 (0.2 %) 0 ▪ Non-neoplastic lesion 21 (3 %) 16 (3 %) ▪ Retrieval failure 33 (4 %) 6 (1 %) Retrieval 0.001 ▪ Success 771 (96%) 524 (99%) ▪ Failure 33 (4 %) 6 (1 %) 4 1 Horizontal margin 0.1 ▪ Clear 530 (76%) 424 (80%) ▪ Positive 10 1 ▪ Negative 520 423 ▪ Unclear 168 (24%) 106 (20%) Clipping for disclosure < 0.001 ▪ None 752 (94 %) 109 (21 %) ▪ Clipping 52 (6 %) 421 (79 %) CSP, cold snare polypectomy; HP, hot snare polypectomy χ2test Mann-Whitney U test Fisher's exact test only adenomatous lesions were analyzed. Yamashina Takeshi et al. Cold snare polypectomy … Endoscopy International Open 2017; 05: E587–E594 E590 This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited. Table 3 Characteristics of the patients and lesions after propensity score-matching. CSP group HP group P value Patients 231 177 ▪ (Male/Female) (138 /93) (122 /55) Antithrombotic therapy < 0.006 ▪ None or discontinuation 221 177 ▪ Continuation 10 177 Polyps 402 402 Location 1.0 ▪ Right-side colon 208 (52 %) 208 (52 %) ▪ Left-side colon 168 (42 %) 168 (42 %) ▪ Rectum 26 (6 %) 26 (6 %) Morphology 1.0 ▪ Pedunculated type 9 (2 %) 9 (2 %) ▪ Semipedunculated type 82 (20 %) 82 (20 %) ▪ Sessile type 221 (55%) 221 (55%) ▪ Superficial elevated type 90 (22 %) 90 (22 %) Median tumor size (range, mm) 5 (2 – 11) 5 (2 – 11) 1.0 Retrieval 0.01 ▪ Success 388 (97%) 399 (99%) ▪ Failure 14 (3 %) 3 (1 %) 4 2 Horizontal margin < 0.001 ▪ Clear 282 (77%) 325 (90%) ▪ Positive 8 1 ▪ Negative 274 324 ▪ Unclear 83 (23 %) 38 (10 %) Clipping for disclosure 38 (9 %) 325 (81 %) < 0.001 ▪ None 364 (91 %) 77 (19 %) CSP, cold snare polypectomy; HP, hot snare polypectomy Fisher's exact test 2 2 χ test Mann-Whitney U test only adenomatous lesions were analyzed. patients received antithrombotic agents in CSP group. With re- Discussion gard to treatment outcomes, the DPPB rate for colorectal polyps was significantly higher in the HP group than in the CSP CSP is a polypectomy method that has gained considerable no- group (0.02% vs 0%, P = 0.04)( Table 4). The HP group had a toriety in recent years, as it is a safe and efficient method for significantly larger number of clips used for closure of the mu- small polyps. In this study, we removed 804 polyps, easily and cosal defect or hemoclip (81 % vs 9 %, P < 0.001). Significantly safely, including those of 18 patients (73 polyps) on single an- more patients in the CSP group had unclear horizontal margin tithrombotic therapy. There was no increase in the rate of AEs, precluding its assessment (83 vs 38 cases, P < 0.001). The retrie- and particularly, there were no cases of DPPB in the CSP group. val failure rate was significantly higher in the CSP group than in Furthermore, we used propensity score-matching analysis be- the HP group (3 % vs 0.7 %, P = 0.01). tween the CSP and HP groups to reduce or minimize the effects of sampling bias (location, size and morphology) in non-ran- domized studies [20]. As a result, we showed that CSP is signif- icantlysuperior toHPinreducing DPPB after colorectal polyp Yamashina Takeshi et al. Cold snare polypectomy … Endoscopy International Open 2017; 05: E587–E594 E591 This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited. Original article this may have resulted from the small crushed specimens which Table 4 Adverse events. stem largelyfromour nothavingused a dedicatedcoldsnare. CSP group HP group P value This outcome could be improved by more extensive mucosal resection or modifying the existing cold snare. However, Adverse events n = 330 n = 209 endoscopists should always keep in mind the difficulty of ▪ Delayed bleeding 0 4 0.02 pathological margin assessment with CSP. Furthermore, in the CSP group, polyp retrieval failure has be- ▪ Perforation 0 0 1.0 come an issue [34, 35]. In our study, the polyp retrieval failure Adverse events after pro- n= 231 n=177 rate was 4 %, and polyp retrieval failure was significantly more pensity score-matching frequent in the CSP group even after propensity score match- ▪ Delayed bleeding 0 4 0.04 ing analysis. Although we couldn't investigate in this study, ▪ Perforation 0 0 1.0 this may be because the size of the resected specimen obtained with CSP is smaller than that obtained with HP by submucosal CSP, cold snare polypectomy; HP, hot snare polypectomy Fisher's exact test injection even though the tumor size is the same. Moreover, after CSP, there is more or less immediate bleeding, which may impair the endoscopic visibility. It was suggested in some endoscopic resection. Although in previous reports, DPPB oc- reports that immediate polyp retrieval by suction or by pulling curred less commonly after CSP [15 – 18], this is the first study the polyp into the colonoscope channel, then transecting it to show this result in a large sample of patients/polyps by using while suctioning, yielded a high rate of polyp retrieval [35, 36]. propensity score matching analysis. In other words, if patients However, all endoscopists need to be extremely careful while undergo HP in these clinical setting, it would cause significantly performing the polyp retrieval. more DPPB than CSP. Hence our findings indicate that CSP is re- We underwent clipping when the mucosal defects were commended polypectomy in these clinical setting. large or if blood was spurting immediately. Some reports de- In general, the incidence of DPPB after HP has been report- scribed that prophylactic clipping prevent DPPB [37 – 39]. In edly higher in patients receiving anticoagulation therapy [23, contrast, some studies have demonstrated that there was no 24] even though warfarin is interrupted prior to the HP proce- difference [40 – 43]. In this study, the HP group had a signifi- dure [25]. However, Horiuchi et al. also reported that DPPB re- cantly larger number of clips used for closure of the mucosal quiring hemostasis occurred significantly less frequently after defect. However, there is significantly higher rate of DPPB in CSP than it did after HP despite continuation of anticoagulants. HP group. Many factors will affect DPPB and it is still controver- [17] In our study, we were able to remove polyps safely in eigh- sial. teen patients on single anticoagulant therapy. We therefore Our study had some limitations. First, although the study consider that CSP has the potential to safely remove subcenti- participants were prospectively enrolled into our database, the metric polyps in patients receiving single anticoagulant ther- detailed data of the patients were retrospectively collected apy. Conversely, in the guidelines of The American Society for from medical records. Of course, we routinely use the same Gastrointestinal Endoscopy and The European Society of Gas- care plan for all patients undergoing HP or CSP and symptoms trointestinal Endoscopy, the risk of DPPB is low among patients were recorded routinely. However, we cannot exclude the pos- undergoing HP and being treated with aspirin as antiplatelet sibility of missing data in some medical records regarding pa- monotherapy [26, 27]. However, patients receiving thienopyri- tients’ symptoms, such as minor delayed bleeding. Second, dines were recommended to be treated as having a high risk of this study was conducted in a single municipal hospital. Al- DPPB [26, 27] and some reports suggested that the DPPB rate though using a standardized protocol for CSP and perioperative of HP was higher in the group that continued to use thienopyr- management can provide pure results, the number of DPPB pa- idines [28, 29]. Although Repici et al. reported that single anti- tients is insufficient because of the rate of DPPB is relatively platelet therapy was an independent predictor of immediate low. And we may be not able to properly assess DPPB outcomes. postpolypectomy bleeding, their patients underwent CSP, in- This should be further evaluated in a future multicenter study. cluding 33 patients on thienopyridines, and there were no Further data in the area of optimal endoscopic technique for cases of DPPB [16]. This was comparable with our study results patients prescribed antithrombotic agents are necessary to in that we were able to remove nine polyps safely in patients on better inform endoscopy-related decisions and implement the single thienopyridine therapy. In our study, we excluded pa- best clinical practices. Third, we excluded the patients under- tients taking two antithrombotic agents; such patients should going HP and CSP during the same session to avoid confusion therefore be further evaluated in a future multicenter study. in terms of which procedure was attributable for the DPPB. Some studies reported that the rate of histologic eradication However, previous reports indicated that the rate of DPPB of of CSP was 93.2 % to 99 % [15, 30, 31]. This is a high rate, equal CSP was 0 – 1.8 % [15 – 18] and our incidence of DPPB was 0 %. to that of HP [32]. In previous reports, the evaluable horizontal Consequently, it is considered a negligible risk if DPPB occurred margin rate of CSP was 42.2 % to 60 % [15, 33], lower than that in patients undergoing HP and CSP during the same session. of the HP [33]. In our study, although we achieved a lower pro- Forth, there would be a possibility of inter-operator variability. portion of cases of positive horizontal margin (1.4 %), there Although all colonoscopists who participated in this study un- were 24 % of cases of unclear horizontal margin. We believe derwent both CSP and HP, some colonoscopists may prefer Yamashina Takeshi et al. Cold snare polypectomy … Endoscopy International Open 2017; 05: E587–E594 E592 This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited. [11] Tappero G, Gaia E, De Giuli P et al. Cold snare excision of small colo- CSP to HP and conversely. However, CSP and HP is a simple and rectal polyps. Gastrointest Endosc 1992; 38: 310 – 313 well established method, we thought it may be negligible effect [12] Waye JD. New methods of polypectomy. Gastrointest Endosc Clin N on DPPB. This would be also further evaluated in a future multi- Am 1997; 7: 413 – 422 center study. [13] Uno Y, Obara K, Zheng P et al. Cold snare excision is a safe method for diminutive colorectal polyps. Tohoku J Exp Med 1997; 183: 243 – 249 [14] Ichise Y, Horiuchi A, Nakayama Y et al. Prospective randomized com- Conclusion parison of cold snare polypectomy and conventional polypectomy for In conclusion, CSP is a safe method for the removal of subcenti- small colorectal polyps. Digestion 2011; 84: 78 – 81 meter polyps, and it is even a safe method for the removal of [15] Takeuchi Y, Yamashina T, Matsuura N et al. Feasibility of cold snare these lesions in patients receiving single anticoagulant therapy polypectomy in Japan: A pilot study. World J. Gastrointest Endosc 2015; 7: 1250 – 1256 or single antiplatelet therapy. Moreover, we showed by a pro- pensity score-matching model that DPPB occurred with less [16] Repici A, Hassan C, Vitetta E et al. Safety of cold polypectomy for < 10 mm polyps at colonoscopy : a prospective multicenter study. frequency after CSP than it did after HP. Our findings indicate Endoscop 2012; 44: 27 – 31 that CSP is recommended polypectomy in daily clinical setting. [17] Horiuchi A, Nakayama Y, Kajiyama M et al. Removal of small colorectal However, special care should be taken during polyp retrieval polyps in anticoagulated patients: a prospective randomized com- and horizontal margin assessment, and these issues could be parison of cold snare and conventional polypectomy. Gastrointest taken into account in follow-up after CSP. Endosc 2014; 79: 417 – 423 [18] Park S-K, Ko BM, Han JP et al. A prospective randomized comparative study of cold forceps polypectomy by using narrow-band imaging Acknowledgements endoscopy versus cold snare polypectomy in patients with diminutive The authors thank all endoscopists and our colleagues at the colorectal polyps. Gastrointest Endosc 2016; 83: 527 – 532 Department of Gastroenterology and Hepatology, Osaka Red [19] Paspatis GA, Tribonias G, Konstantinidis K et al. A prospective ran- Cross Hospital, who supported this study. domized comparison of cold vs hot snare polypectomy in the occur- rence of postpolypectomy bleeding in small colonic polyps. Colorec- tal Dis 2011; 13: 345 – 348 Competing interests [20] Rosenbaum PR, Rubin DB. The central role of the propensity score in observational studies for causal effects. Biometrika 1983; 70: 41 – 55 [21] von Elm E, Altman DG, Egger M et al. The Strengthening the Report- None ing of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. 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Ther 2013; 37: 947 – 952 [10] Choung BS, Kim SH, Ahn DS et al. Incidence and risk factors of delayed [30] Lee CK, Shim J-J, Jang JY. Cold snare polypectomy vs. Cold forceps postpolypectomy bleeding: a retrospective cohort study. J Clin Gas- polypectomy using double-biopsy technique for removal of diminu- troenterol 2014; 48: 784 – 789 tive colorectal polyps: a prospective randomized study. Am. J. Gas- troenterol 2013; 108: 1593 – 1600 Yamashina Takeshi et al. Cold snare polypectomy … Endoscopy International Open 2017; 05: E587–E594 E593 This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited. Original article [31] Kim JS, Lee B-I, Choi H et al. Cold snare polypectomy versus cold for- [38] Matsumoto M, Fukunaga S, Saito Y et al. Risk factors for delayed ceps polypectomy for diminutive and small colorectal polyps: a ran- bleeding after endoscopic resection for large colorectal tumors. Jpn. domized controlled trial. Gastrointest. Endosc 2015; 81: 741 – 747 J. Clin. Oncol 2012; 42: 1028 – 1034 [32] Pohl H, Srivastava A, Bensen SP et al. Incomplete polyp resection [39] Zhang Q-S, Han B, Xu J-H et al. Clip closure of defect after endoscopic during colonoscopy-results of the complete adenoma resection resection in patients with larger colorectal tumors decreased the ad- (CARE) study. Gastroenterology 2013; 144: 74 – 80 verse events. Gastrointest. Endosc 2015; 82: 904 – 909 [33] Saito D, Hayashida M, Miura M et al. A comparative study between [40] Shioji K, Suzuki Y, Kobayashi M et al. Prophylactic clip application does cold nare polypectomy and endoscopic mucosal resection for resec- not decrease delayed bleeding after colonoscopic polypectomy. Gas- tion of colorectal polyps. (In Japanese with English abstract.). Gastro- trointest. Endosc 2003; 57: 691 – 694 enterol. Endosc 2016; 58: 32 – 37 [41] Boustière C, Veitch A, Vanbiervliet G et al. Endoscopy and antiplatelet [34] Komeda Y, Suzuki N, Sarah M et al. Factors associated with failed agents. European Society of Gastrointestinal Endoscopy (ESGE) polyp retrieval at screening colonoscopy. Gastrointest. Endosc 2013; Guideline. Endoscopy 2011; 43: 445 – 461 77: 395 – 400 [42] Matsumoto M, Kato M, Oba K et al. Multicenter randomized con- [35] Fernandes C, Pinho R, Ribeiro I et al. Risk factors for polyp retrieval trolled study to assess the effect of prophylactic clipping on post-po- failure in colonoscopy. United Eur. Gastroenterol. J 2015; 3: 387 – 392 lypectomy delayed bleeding. Dig. Endosc 2016; 28: 570 – 576 [36] Deenadayalu VP, Rex DK. Colon polyp retrieval after cold snaring. [43] Dokoshi T, Fujiya M, Tanaka K et al. A randomized study on the effec- Gastrointest. Endosc 2005; 62: 253 – 256 tiveness of prophylactic clipping during endoscopic resection of colon polyps for the prevention of delayed bleeding. Biomed Res. Int 2015; [37] Liaquat H, Rohn E, Rex DK. Prophylactic clip closure reduced the risk 02: 1 – 6 of delayed postpolypectomy hemorrhage: experience in 277 clipped large sessile or flat colorectal lesions and 247 control lesions. Gastro- intest. Endosc 2013; 77: 401 – 407 Yamashina Takeshi et al. Cold snare polypectomy … Endoscopy International Open 2017; 05: E587–E594 E594 This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Endoscopy International Open Pubmed Central

Cold snare polypectomy reduced delayed postpolypectomy bleeding compared with conventional hot polypectomy: a propensity score-matching analysis

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Pubmed Central
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2364-3722
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10.1055/s-0043-105578
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Abstract

Original article Cold snare polypectomy reduced delayed postpolypectomy bleeding compared with conventional hot polypectomy: a propensity score-matching analysis Authors Takeshi Yamashina, Manabu Fukuhara, Takanori Maruo, Gensho Tanke, Saiko Marui, Ryota Sada, Mio Taki, Yoshiaki Ohara, Azusa Sakamoto, Shinichiro Henmi, Yugo Sawai, Sumio Saito, Norihiro Nishijima, Akihiro Nasu, Hideyuki Komekado, Akira Sekikawa, Masanori Asada, Takehiko Tumura, Ryuichi Kita, Toru Kimura, Yukio Osaki Institution DPPB after CSP and compare it with that of HP. A propensity Department of Gastroenterology and Hepatology, Osaka score model was used as a secondary analysis. Red Cross Hospital, Osaka, Japan Patients and methods This was a retrospective cohort study conducted in a single municipal hospital. We identi- submitted 21.8.2016 fied 539 patients with colorectal polyps from 2 mm to 11 accepted after revision 10.2.2017 mm in size who underwent CSP (804 polyps in 330 patients) or HP (530 polyps in 209 patients) between July 2013 and Bibliography June 2015. DOI https://doi.org/10.1055/s-0043-105578 | Results There were no cases of DPPB in the CSP group. Endoscopy International Open 2017; 05: E587–E594 Conversely, DPPB occurred in 4 patients (1.9 %) after HP, re- © Georg Thieme Verlag KG Stuttgart · New York sulting in a significant difference between the CSP and HP ISSN 2364-3722 groups (0.008 % vs 0 %, P = 0.02). Propensity score-match- ing analysis created 402 matched pairs, yielding a signifi- Corresponding author cantly higher DPPB rate in the HP group than CSP group Takeshi Yamashin, Department of Gastroenterology and (0.02 % vs 0 %, P = 0.04). However, significantly more pa- Hepatology, Osaka Red Cross Hospital, Osaka, Japan, tients in the CSP group had unclear horizontal margins 30 Fudegasaki, Tenouji, Osaka 543-8555, Japan that precluded assessment (83 vs 38 cases, P < 0.001). The Fax: (+81) 6-(6774)-5131 retrieval failure rate was significantly higher in the CSP [email protected] group than in the HP group (3 % vs 0.7 %, P = 0.01). Conclusions DPPB waslessfrequent withCSP than HP,as ABSTRACT selected by the propensity score-matching model. Our findings indicate that CSP is recommended polypectomy in Background and study aims Cold snare polypectomy daily clinical setting. However, special care should be taken (CSP) for small colorectal polyps has lower incidence of ad- during polyp retrieval and horizontal margin assessment, verse events, especially delayed postpolypectomy bleeding and these issues could be taken into account in follow-up (DPPB). However, few data are available on comparisons of after CSP. the incidence of DPPB of CSP and hot polypectomy (HP). The aim of this study was to evaluate the incidence of with electrocautery to remove colorectal polyps. However, Introduction two major adverse events (AEs), delayed post-polypectomy Colorectal carcinoma (CRC) is the fourth-most-common cause bleeding (DPPB) and perforation have remained an issue. In of cancer-related mortality worldwide [1] , and it is the third- previous reports, the incidence of DPPB of HP was 0.6 % to 2 % most-common cancer, with nearly 1.4 million new cases in [5 – 10]. Moreover, polyp size, shape, and location are risk fac- 2012 [2] . Most cases originate from adenomas [3] and their re- tors for DPPB [6, 10]. moval reduces the risk of death from CRC [4]. Therefore, if ade- In contrast, as far back as 20 years ago, cold snare polypec- nomas and cancers are detected early in their development, tomy (CSP) for small colorectal polyps has been reported to be they can be cured by endoscopic therapy. a safe and effective polyp removal method without electrocau- Hot polypectomy (HP), including hot snare polypectomy, tery [11 – 13]. This method is also superior to conventional po- endoscopic mucosal resection (EMR) and hot biopsy polypecto- lypectomy in terms of procedure time [14]. Thus, currently, CSP my, are the most commonly performed endoscopic therapies has gained notoriety. Moreover, the incidence of DPPB was re- Yamashina Takeshi et al. Cold snare polypectomy … Endoscopy International Open 2017; 05: E587–E594 E587 This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited. Original article ported to be 0 % to 1.8 % for CSP in previous prospective studies ways supervised the procedure in introduction period. The [15 –19], whichtends to be lower thanthat ofHP eveninpa- polyp was snared, including normal surrounding mucosa and tients that continued to receive anticoagulant treatment [17]. the snare was closed for transection of the polyp without elec- However, a previous study included only a small number of pa- trocautery. HP was performed with a similar type of videoendo- tients, and few studies have compared the incidence of DPPB of scope used for polypoid lesions. The same colonoscopists that CSP and HP in daily clinical setting. performed CSP mainly used the XEMEX Bipolar Snare S DRAGO- Randomized controlled trials are the most effective way of NARE™ (Xemex, Tokyo, Japan) to perform HP. As for EMR, nor- scientifically testing new medical interventions. However, the mal saline is injected into the submucosa before excision. The rate of DPPB is relatively low, and many cases are needed to Intelligent Cut and Coagulation 200 (ERBE Elektromedizin, Tü- conduct randomized controlled trials. Paspatis et al. conducted bingen, Germany) or VIO 300 D (ERBE) was used as a power a randomized controlled trial comparing CSP with hot snare HP source for electrical bipolar cutting and bipolar coagulation, in the occurrence of DPPB [19]. However, they didn’tstratify by and all participant endoscopists used the same setting. Before polyp size, and in it was significantly larger in the HP group than February 2014, we conventionally underwent clipping in most the CSP group and there was no DPPB in either group. Recently, HP cases. From that time onwards, the mucosal defects after propensity score matching has become a popular alternative to CSP or HP were large or if blood was spurting immediately, the randomized controlled trials [20]. We therefore hypothesized mucosal defect was closed using endoscopic clips. Usually, CSP that it would be more effective to use propensity score match- was performed as an outpatient procedure. And as many other ing analysis to compare CSP directly with HP. The aim of this Japanese hospitals, HP usually required a two-day hospitaliza- study was to evaluate the incidence of DPPB after colorectal tion. In general, most of Japanese patients who undergo poly- CSP and compare it with that after HP. Additionally, we per- pectomy or EMR are hospitalized for a few days. All patients un- formed secondary analysis with a propensity score model. derwent postoperative follow-up hospital visits about two weeks after polypectomy. Patients and methods Propensity score matching analysis Patients To reduce the possibility of selection bias and to identify control This retrospective cohort study was performed in a single mu- subjects, we performed propensity score matching with a ratio nicipal hospital. We identified consecutive patients with colo- of 1:1 and nearest neighbor matching without replacement rectal polyps from 2 mm to 11 mm in size who underwent CSP within a caliper width of 0.02 and the polyps for which the pro- or HP between July 2013 and June 2015 in our prospectively pensity score could not be matched because of a greater caliper maintained database of Osaka Red Cross Hospital, and enrolled distance were excluded from further analysis. To estimate the them into this analysis. Before February 2014, we mainly per- propensity score, we used a logistic regression model. Factors formed HP and after February 2014, we mainly performed CSP. related to DPPB have been previously reported to be polyp si- Patients with colorectal polyps larger than 5 mm who were re- zes, polyps located in the right-sided colon and polyp shape commended to undergo polypectomy and all polyps resected [6, 10]. Hence, variables included in the propensity score model endoscopically during screening colonoscopies were included were polyp size, polyp location (right-sided colon vs left-sided in the study. Patients who underwent colorectal HP and CSP colon) and polyp shape (Ip and Isp vs Is and IIa). procedures during operation or patients with perforation dur- Data analysis and definition of outcomes ing the procedure were excluded. This manuscript was prepar- ed accordingto the Strengtheningthe ReportingofObserva- The procedural details were recorded prospectively in a data- tional Studies in Epidemiology (STROBE) Statement [21]. base and their medical records were thoroughly investigated. The collected data included patient age, gender (male or fe- Endoscopic procedure and perioperative male), location (cecum, ascending colon, transverse colon, des- management cending colon, sigmoid colon, or rectum), tumor size, morpho- CSP or HP was performed under intravenous sedation with mid- logical type, and histological type (adenoma or serrated le- azolam. During colonoscope withdrawal, polyp location was sions, or carcinoma). The characteristics of lesions in the CSP documented and size was measured using biopsy forceps with group were compared with those in the HP group. Primary end- a 2.2-mm outer diameter or snares with an outer diameter of point of this study was DPPB rate after colorectal CSP and com- 11 mm to 20 mm. The phenotypes of polyps were classified ac- pare it with that after HP. Other AEs, retrieval failure rate and cording to the Paris classification [22]. Before polypectomy, horizontal margin were evaluated as secondary endpoints. chromoendoscopy or magnifying endoscopy was performed to DPPB was defined as hemochezia occurring > 24 hours after exclude the non-neoplastic lesions. The CSP was performed colorectal polypectomy that required an endoscopic hemostat- with a videoendoscope (CF-HQ290, PCF-PQ260 L, Olympus ic procedure. Medical Systems, Tokyo, Japan) for small (≤ 11 mm) polypoid le- Statistical analysis sions using Profile™ Polypectomy Snares (Boston Scientific Ja- pan, Tokyo, Japan) by 15 experienced colonoscopists who have The Fisher’sexact test or χ test was used for analysis of catego- sufficient expertise and experience of colorectal polypectomy. rical data. Quantitative data were compared using the Stu- They all thoroughly experienced CSP or otherwise specialists al- dent’s t test or Mann-Whitney U test. P<0.05 (two-sided) was Yamashina Takeshi et al. Cold snare polypectomy … Endoscopy International Open 2017; 05: E587–E594 E588 This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited. botic agents: aspirin; 8, clopidogrel; 3, cilostazol; 2, aspirin-dia- luminate;1,sarpogrelate; 1, limaprost alfadex; 1, apixaban; 1, 765 patients with colorectal polyp treated between July 2013 and June 2015 rivaroxaban; 1. Conversely in total 530 polyps in 209 patients were included in our analysis of HP group (Polypectomy: 329, Excluded EMR: 181, Hot biopsy: 20), and the baseline characteristics are ▪ polyps >11 mm n = 194 ▪ underwent HP and CSP presented in Table 1. Patients comprised 142 men and 69 n = 27 womenwithamedian age(range) of 66 (30 – 91) years. The ▪ With two antithrombotic agents n = 2 median resected tumor size (range) was 5 (2 – 11) mm, and ▪ No meticulous operative the lesions were located in the cecum, ascending colon, trans- record n = 3 verse colon, descending colon, sigmoid colon, and rectum in 28, 105, 123, 57, 169, and 49 cases, respectively. In the HP CSP n = 330 HP n = 209 group, eight patients discontinued the antithrombotic therapy and none of the patients continued the antithrombotic therapy. No differences were observed in gender, age, location or mor- ▶ Fig. 1 Flow diagram. CSP, cold snare polypectomy; HP, hot poly- phology between the CSP and HP groups (▶Table 2). pectomy Procedure-related outcomes In this study, therewerenocases of DPPB in theCSP group. considered significant. All statistical analyses were carried out Otherwise, although two cases were used clips for closure of using SPSS statistics version 23 (SPSS, Chicago, IL, USA). the mucosal defect, DPPB occurred in four patients (1.9 %) who underwent HP in different colonoscopists for colorectal polyps, resulting in a significant difference between the CSP Results and HP groups (0.008 % vs 0 %, P = 0.02). However, the HP group Baseline data had a significantly larger median resected polyp size (4 mm vs During the study period, 765 patients with colorectal polyps 5 mm, P = 0.01). There was no statistically significant differ- were treated by CSP or HP at the Osaka Red Cross Hospital dur- ence in histological type of polyp or assessment of the hori- ing the study period. A total of 226 patients were excluded zontal margin between the groups. The HP group had a signif- from the analysis because they had polyps > 11 mm (n = 194), icantly larger number of clips used for closure of the mucosal underwent another colorectal HP at the same time (n = 27), defect or hemoclip (79 % vs 6 %, P < 0.001). The retrieval failure continued treatment with two antithrombotic agents (n = 2) or rate was significantly higher in the CSP group than in the HP had no meticulous operative record (n = 3). A flow diagram of group (4 % vs 1 %, P = 0.001). All DPPB cases were managed the participants is shown in Fig. 1. In total, 804 polyps in 330 conservatively with the endoscopic hemostatic procedure and patients were included in our analysis of CSP group, and the no other serious AEs, such as perforation or postpolypectomy baseline characteristics are presented in ▶Table 1.Patients syndrome, were observed in either group. comprised 196 men and 134 women with a median age (range) Procedure-related outcomes after propensity score of 68 (27 – 91) years. The median resected tumor size (range) matching was 4 (2 – 11) mm, and the lesions were located in the cecum, ascending colon, transverse colon, descending colon, sigmoid The matching factors and treatment outcomes between the colon, and rectum in 50, 197, 203, 82, 206, and 66 cases, CSP and HP groups after propensity score matching are shown respectively (▶Table 2). Eighteen patients received antithrom- in ▶Table 3. Four hundred and two pairs were matched. Ten Table 1 Baseline characteristics of patients (n = 539). CSP group HP group P value Patients 330 209 0.07 ▪ Male (%) 196 (59 %) 142 (68 %) ▪ Female (%) 134 (41 % 69 (32 %) Median age (range, years) 68 (27 – 91) 66 (30 – 91) 1.0 Antithrombotic therapy < 0.001 ▪ None or discontinuation 312 209 ▪ Continuation 18 0 CSP, cold snare polypectomy; HP, hot snare polypectomy 1 2 χ test Student’s t test. Yamashina Takeshi et al. Cold snare polypectomy … Endoscopy International Open 2017; 05: E587–E594 E589 This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited. Original article Table 2 Baseline characteristics of lesions. CSP group HP group P value (n = 804) (n = 530) Location 0.3 ▪ Cecum 50 (6 %) 28 (5 %) ▪ Ascending colon 197 (25 %) 105 (20 %) ▪ Transverse colon 203 (25 %) 122 (23 %) ▪ Descending colon 82 (10 %) 57 (11 %) ▪ Sigmoid colon 206 (26 %) 169 (32 %) ▪ Rectum 66 (8 %) 49 (9 %) Morphology 0.6 ▪ Pedunculated type 16 (2 %) 24 (5 %) ▪ Semipedunculated type 130 (16 %) 132 (25 %) ▪ Sessile type 548 (68%) 239 (45%) ▪ Superficial elevated type 110 (14 %) 130 (25 %) ▪ Superficial depressed type 0 2 (0.4 %) ▪ Submucosal tumor 0 3 (0.6 %) Median tumor size (range, mm) 4 (2 – 11) 5 (2 – 11) 0.01 Histological type 0.1 ▪ Adenocarcinoma 0 (0 %) 12 (2 %) ▪ Adenoma 685 (85 %) 445 (84 %) ▪ Hyperplastic polyp 52 (6 %) 37 (7 %) ▪ Sessile serrated adenoma polyp 11 (1 %) 11 (2 %) ▪ Traditional serrated polyp 2 (0.2 %) 0 ▪ Non-neoplastic lesion 21 (3 %) 16 (3 %) ▪ Retrieval failure 33 (4 %) 6 (1 %) Retrieval 0.001 ▪ Success 771 (96%) 524 (99%) ▪ Failure 33 (4 %) 6 (1 %) 4 1 Horizontal margin 0.1 ▪ Clear 530 (76%) 424 (80%) ▪ Positive 10 1 ▪ Negative 520 423 ▪ Unclear 168 (24%) 106 (20%) Clipping for disclosure < 0.001 ▪ None 752 (94 %) 109 (21 %) ▪ Clipping 52 (6 %) 421 (79 %) CSP, cold snare polypectomy; HP, hot snare polypectomy χ2test Mann-Whitney U test Fisher's exact test only adenomatous lesions were analyzed. Yamashina Takeshi et al. Cold snare polypectomy … Endoscopy International Open 2017; 05: E587–E594 E590 This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited. Table 3 Characteristics of the patients and lesions after propensity score-matching. CSP group HP group P value Patients 231 177 ▪ (Male/Female) (138 /93) (122 /55) Antithrombotic therapy < 0.006 ▪ None or discontinuation 221 177 ▪ Continuation 10 177 Polyps 402 402 Location 1.0 ▪ Right-side colon 208 (52 %) 208 (52 %) ▪ Left-side colon 168 (42 %) 168 (42 %) ▪ Rectum 26 (6 %) 26 (6 %) Morphology 1.0 ▪ Pedunculated type 9 (2 %) 9 (2 %) ▪ Semipedunculated type 82 (20 %) 82 (20 %) ▪ Sessile type 221 (55%) 221 (55%) ▪ Superficial elevated type 90 (22 %) 90 (22 %) Median tumor size (range, mm) 5 (2 – 11) 5 (2 – 11) 1.0 Retrieval 0.01 ▪ Success 388 (97%) 399 (99%) ▪ Failure 14 (3 %) 3 (1 %) 4 2 Horizontal margin < 0.001 ▪ Clear 282 (77%) 325 (90%) ▪ Positive 8 1 ▪ Negative 274 324 ▪ Unclear 83 (23 %) 38 (10 %) Clipping for disclosure 38 (9 %) 325 (81 %) < 0.001 ▪ None 364 (91 %) 77 (19 %) CSP, cold snare polypectomy; HP, hot snare polypectomy Fisher's exact test 2 2 χ test Mann-Whitney U test only adenomatous lesions were analyzed. patients received antithrombotic agents in CSP group. With re- Discussion gard to treatment outcomes, the DPPB rate for colorectal polyps was significantly higher in the HP group than in the CSP CSP is a polypectomy method that has gained considerable no- group (0.02% vs 0%, P = 0.04)( Table 4). The HP group had a toriety in recent years, as it is a safe and efficient method for significantly larger number of clips used for closure of the mu- small polyps. In this study, we removed 804 polyps, easily and cosal defect or hemoclip (81 % vs 9 %, P < 0.001). Significantly safely, including those of 18 patients (73 polyps) on single an- more patients in the CSP group had unclear horizontal margin tithrombotic therapy. There was no increase in the rate of AEs, precluding its assessment (83 vs 38 cases, P < 0.001). The retrie- and particularly, there were no cases of DPPB in the CSP group. val failure rate was significantly higher in the CSP group than in Furthermore, we used propensity score-matching analysis be- the HP group (3 % vs 0.7 %, P = 0.01). tween the CSP and HP groups to reduce or minimize the effects of sampling bias (location, size and morphology) in non-ran- domized studies [20]. As a result, we showed that CSP is signif- icantlysuperior toHPinreducing DPPB after colorectal polyp Yamashina Takeshi et al. Cold snare polypectomy … Endoscopy International Open 2017; 05: E587–E594 E591 This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited. Original article this may have resulted from the small crushed specimens which Table 4 Adverse events. stem largelyfromour nothavingused a dedicatedcoldsnare. CSP group HP group P value This outcome could be improved by more extensive mucosal resection or modifying the existing cold snare. However, Adverse events n = 330 n = 209 endoscopists should always keep in mind the difficulty of ▪ Delayed bleeding 0 4 0.02 pathological margin assessment with CSP. Furthermore, in the CSP group, polyp retrieval failure has be- ▪ Perforation 0 0 1.0 come an issue [34, 35]. In our study, the polyp retrieval failure Adverse events after pro- n= 231 n=177 rate was 4 %, and polyp retrieval failure was significantly more pensity score-matching frequent in the CSP group even after propensity score match- ▪ Delayed bleeding 0 4 0.04 ing analysis. Although we couldn't investigate in this study, ▪ Perforation 0 0 1.0 this may be because the size of the resected specimen obtained with CSP is smaller than that obtained with HP by submucosal CSP, cold snare polypectomy; HP, hot snare polypectomy Fisher's exact test injection even though the tumor size is the same. Moreover, after CSP, there is more or less immediate bleeding, which may impair the endoscopic visibility. It was suggested in some endoscopic resection. Although in previous reports, DPPB oc- reports that immediate polyp retrieval by suction or by pulling curred less commonly after CSP [15 – 18], this is the first study the polyp into the colonoscope channel, then transecting it to show this result in a large sample of patients/polyps by using while suctioning, yielded a high rate of polyp retrieval [35, 36]. propensity score matching analysis. In other words, if patients However, all endoscopists need to be extremely careful while undergo HP in these clinical setting, it would cause significantly performing the polyp retrieval. more DPPB than CSP. Hence our findings indicate that CSP is re- We underwent clipping when the mucosal defects were commended polypectomy in these clinical setting. large or if blood was spurting immediately. Some reports de- In general, the incidence of DPPB after HP has been report- scribed that prophylactic clipping prevent DPPB [37 – 39]. In edly higher in patients receiving anticoagulation therapy [23, contrast, some studies have demonstrated that there was no 24] even though warfarin is interrupted prior to the HP proce- difference [40 – 43]. In this study, the HP group had a signifi- dure [25]. However, Horiuchi et al. also reported that DPPB re- cantly larger number of clips used for closure of the mucosal quiring hemostasis occurred significantly less frequently after defect. However, there is significantly higher rate of DPPB in CSP than it did after HP despite continuation of anticoagulants. HP group. Many factors will affect DPPB and it is still controver- [17] In our study, we were able to remove polyps safely in eigh- sial. teen patients on single anticoagulant therapy. We therefore Our study had some limitations. First, although the study consider that CSP has the potential to safely remove subcenti- participants were prospectively enrolled into our database, the metric polyps in patients receiving single anticoagulant ther- detailed data of the patients were retrospectively collected apy. Conversely, in the guidelines of The American Society for from medical records. Of course, we routinely use the same Gastrointestinal Endoscopy and The European Society of Gas- care plan for all patients undergoing HP or CSP and symptoms trointestinal Endoscopy, the risk of DPPB is low among patients were recorded routinely. However, we cannot exclude the pos- undergoing HP and being treated with aspirin as antiplatelet sibility of missing data in some medical records regarding pa- monotherapy [26, 27]. However, patients receiving thienopyri- tients’ symptoms, such as minor delayed bleeding. Second, dines were recommended to be treated as having a high risk of this study was conducted in a single municipal hospital. Al- DPPB [26, 27] and some reports suggested that the DPPB rate though using a standardized protocol for CSP and perioperative of HP was higher in the group that continued to use thienopyr- management can provide pure results, the number of DPPB pa- idines [28, 29]. Although Repici et al. reported that single anti- tients is insufficient because of the rate of DPPB is relatively platelet therapy was an independent predictor of immediate low. And we may be not able to properly assess DPPB outcomes. postpolypectomy bleeding, their patients underwent CSP, in- This should be further evaluated in a future multicenter study. cluding 33 patients on thienopyridines, and there were no Further data in the area of optimal endoscopic technique for cases of DPPB [16]. This was comparable with our study results patients prescribed antithrombotic agents are necessary to in that we were able to remove nine polyps safely in patients on better inform endoscopy-related decisions and implement the single thienopyridine therapy. In our study, we excluded pa- best clinical practices. Third, we excluded the patients under- tients taking two antithrombotic agents; such patients should going HP and CSP during the same session to avoid confusion therefore be further evaluated in a future multicenter study. in terms of which procedure was attributable for the DPPB. Some studies reported that the rate of histologic eradication However, previous reports indicated that the rate of DPPB of of CSP was 93.2 % to 99 % [15, 30, 31]. This is a high rate, equal CSP was 0 – 1.8 % [15 – 18] and our incidence of DPPB was 0 %. to that of HP [32]. In previous reports, the evaluable horizontal Consequently, it is considered a negligible risk if DPPB occurred margin rate of CSP was 42.2 % to 60 % [15, 33], lower than that in patients undergoing HP and CSP during the same session. of the HP [33]. In our study, although we achieved a lower pro- Forth, there would be a possibility of inter-operator variability. portion of cases of positive horizontal margin (1.4 %), there Although all colonoscopists who participated in this study un- were 24 % of cases of unclear horizontal margin. We believe derwent both CSP and HP, some colonoscopists may prefer Yamashina Takeshi et al. Cold snare polypectomy … Endoscopy International Open 2017; 05: E587–E594 E592 This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited. [11] Tappero G, Gaia E, De Giuli P et al. Cold snare excision of small colo- CSP to HP and conversely. However, CSP and HP is a simple and rectal polyps. Gastrointest Endosc 1992; 38: 310 – 313 well established method, we thought it may be negligible effect [12] Waye JD. New methods of polypectomy. Gastrointest Endosc Clin N on DPPB. This would be also further evaluated in a future multi- Am 1997; 7: 413 – 422 center study. [13] Uno Y, Obara K, Zheng P et al. Cold snare excision is a safe method for diminutive colorectal polyps. Tohoku J Exp Med 1997; 183: 243 – 249 [14] Ichise Y, Horiuchi A, Nakayama Y et al. Prospective randomized com- Conclusion parison of cold snare polypectomy and conventional polypectomy for In conclusion, CSP is a safe method for the removal of subcenti- small colorectal polyps. Digestion 2011; 84: 78 – 81 meter polyps, and it is even a safe method for the removal of [15] Takeuchi Y, Yamashina T, Matsuura N et al. Feasibility of cold snare these lesions in patients receiving single anticoagulant therapy polypectomy in Japan: A pilot study. World J. Gastrointest Endosc 2015; 7: 1250 – 1256 or single antiplatelet therapy. Moreover, we showed by a pro- pensity score-matching model that DPPB occurred with less [16] Repici A, Hassan C, Vitetta E et al. Safety of cold polypectomy for < 10 mm polyps at colonoscopy : a prospective multicenter study. frequency after CSP than it did after HP. Our findings indicate Endoscop 2012; 44: 27 – 31 that CSP is recommended polypectomy in daily clinical setting. [17] Horiuchi A, Nakayama Y, Kajiyama M et al. Removal of small colorectal However, special care should be taken during polyp retrieval polyps in anticoagulated patients: a prospective randomized com- and horizontal margin assessment, and these issues could be parison of cold snare and conventional polypectomy. Gastrointest taken into account in follow-up after CSP. Endosc 2014; 79: 417 – 423 [18] Park S-K, Ko BM, Han JP et al. A prospective randomized comparative study of cold forceps polypectomy by using narrow-band imaging Acknowledgements endoscopy versus cold snare polypectomy in patients with diminutive The authors thank all endoscopists and our colleagues at the colorectal polyps. Gastrointest Endosc 2016; 83: 527 – 532 Department of Gastroenterology and Hepatology, Osaka Red [19] Paspatis GA, Tribonias G, Konstantinidis K et al. A prospective ran- Cross Hospital, who supported this study. domized comparison of cold vs hot snare polypectomy in the occur- rence of postpolypectomy bleeding in small colonic polyps. Colorec- tal Dis 2011; 13: 345 – 348 Competing interests [20] Rosenbaum PR, Rubin DB. The central role of the propensity score in observational studies for causal effects. Biometrika 1983; 70: 41 – 55 [21] von Elm E, Altman DG, Egger M et al. The Strengthening the Report- None ing of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. 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Published: Jun 23, 2017

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