Is Submucosal Injection Helpful in Cold Snare Polypectomy for Small Colorectal Polyps?

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Clin Endosc. 2021;54(3):397-403

Publication date (electronic) : 2021 February 9

doi : https://doi.org/10.5946/ce.2020.226

Ji Hyun Song¹, Shai Friedland^,2,3

¹Department of Internal Medicine, Healthcare Research Institute, Seoul National University Hospital Healthcare System Gangnam Center, Seoul, Korea

²Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA

³Division of Gastroenterology, Veterans Affairs Palo Alto Health Care System, Palo Alto, CA, USA

Correspondence: Shai Friedland Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University School of Medicine, 291 Campus Drive, Stanford, CA 94305, USA Tel: +1-650-787-7099, Fax: +1-650-321-7917, E-mail: shai_friedland@yahoo.com

Received 2020 August 18; Revised 2020 October 23; Accepted 2020 October 27.

Abstract

INTRODUCTION

Cold snare polypectomy (CSP) is a safe and effective method to remove small colorectal polyps (5–9 mm) due to the lack of diathermy-related complications, including postpolypectomy syndrome, delayed bleeding, and perforation [1]. Several studies have reported that complete resection rate for CSP is significantly higher than that for cold forceps polypectomy in diminutive and small colorectal polyps [2,3]. A randomized controlled trial reported that complete resection rate for CSP was not lower than that for hot snare polypectomy (HSP) in 4–9 mm colorectal polyps [4]. Another meta-analysis showed that CSP had a shorter procedure time and tended to result in less delayed bleeding than HSP [5].

Recent studies have reported that cold snare polypectomy with submucosal injection (cold snare endoscopic mucosal resection [CS-EMR]) can be used to remove even larger polyps (≥10 mm) [6,7]. A prospective, randomized controlled study in China showed that CS-EMR was safe and effective for the treatment of 6–20 mm colorectal polyps [8]. Another study reported that the efficacy of CS-EMR was comparable to that of EMR for small colon polyps [9]. Polyp pre-lifting with submucosal chromoendoscopy—injection of a colored fluid—can sharply delineate lesion margins and help remove abnormal tissues using a cold snare [9].

However, data on the effect of submucosal injection in CS-EMR have been limited for small polyps by comparing CS-EMR and CSP. Therefore, this study aimed to compare the efficacy and safety of CS-EMR and CSP and to evaluate risk factors for immediate bleeding during the small polyp resection.

PATIENTS AND METHODS

RESULTS

A total of 100 small colorectal polyps were identified in 58 patients. Table 1 shows the patient characteristics. The average age of patients was 67.5 years, predominantly comprised of men, as expected based on the majority-male demographics of the Veterans Administration Hospital. Nearly half of patients (46.6%) were taking antiplatelet agents, mostly aspirin. Two patients received dual antiplatelet therapy (aspirin and clopidogrel). Ten patients (17.2%) were taking anticoagulants: three with warfarin, six with DOACs, and one with low-molecular-weight heparin. One patient was taking both antiplatelets and anticoagulants (ticagrelor and apixaban). A total of 36 patients (62%) had one or more comorbidities, 20 (35%) had diabetes, 14 (24%) had coronary artery disease, 7 (12%) had atrial fibrillation, and 4 (7%) had chronic obstructive pulmonary disease.

Table 1.

Clinical Characteristics of the Patients

Table 2 shows the characteristics of colon polyps along with the comparison of CSP and CS-EMR groups. The mean size of all polyps was 6.39 mm. A total of 60 polyps were classified as the protruded type (Is, Isp, and Ip), and 40 polyps were classified as the flat elevated type (IIa). Two patients had pedunculated polyps, all removed by CS-EMR. Fifty-four polyps were located in the right colon. In majority of patients, bowel preparation was good (segmental BBPS was 2 or 3). The complete resection rate was 92% and 96% in the CSP and CS-EMR groups, respectively, but without statistically significant difference. The total procedure time was significantly longer in the CS-EMR than that in the CSP group (78.76 sec vs. 23.14 sec, p<0.001). Resection and bleeding times were not significantly different between the two groups. According to the histological diagnosis, 79 polyps were adenomas, 9 were hyperplastic polyps, and 4 were serrated adenomas. The proportion of patients taking antiplatelet agents was higher in the CS-EMR group (54% vs. 30%, p=0.025). After polypectomy, 8 patients showed immediate bleeding and 2 showed delayed bleeding. One of them showed both immediate and delayed bleeding, and a total of 9patients had post-polypectomy bleeding (PPB). No differences in the PPB rate were observed between the CSP and CS-EMR groups. No patients had perforation.

Table 2.

Comparison between Cold Snare Polypectomy and Cold Snare Endoscopic Mucosal Resection Group

Results of univariate analyses on risk factors for PPB are summarized in Table 3. DOAC (OR, 24.688; 95% CI, 4.106–148.432) and polyp size (OR, 1.740; 95% CI, 1.060–2.858) were associated with an increased risk of PPB.

Table 3.

Univariate Analysis of Risk Factors for Postpolypectomy Bleeding (n=100)

In multivariate analysis (Table 4), warfarin (OR, 42.334; 95% CI, 1.006–1,781.758) and DOACs (OR=35.244; 95% CI, 3.853–322.397) showed a higher risk of PPB.

Table 4.

Multivariate Analysis of Risk Factors for Postpolypectomy Bleeding

DISCUSSION

Colonoscopic polypectomy can decrease the incidence of and mortality from colorectal cancer [14,15]. Conventional polypectomy uses an electrosurgical current that increases the risk of complications, including bleeding, perforation, and postpolypectomy syndrome [16,17]. Recently, the introduction of CSP, the mechanical resection of colorectal polyps without electrocautery, has attracted attention as a possible alternative [18]. In a recent prospective cohort study, CSP was performed on 1,198 small colorectal polyps, and no patients had delayed bleeding or perforation [19]. Another retrospective cohort study reported that the incidence of delayed PPB was significantly lower in the CSP than that in the HSP group [20]. According to a histological study comparing CSP and HSP specimens, HSP damaged the deep layers of the colon wall involving larger vessels, whereas CSP was limited to the shallow submucosa, which would be the reason for decreased incidence of delayed bleeding after CSP [21]. The European Society of Gastrointestinal Endoscopy (ESGE) clinical guidelines also recommend CSP as a resection technique for sessile or flat small colorectal polyps [22].

Submucosal injection before HSP provides a thermal safety cushion and makes defining the lesion margin easy [16]. Although injection for thermal safety is not required with CSP, submucosal injection may be helpful to resect polyps by sharply delineating the polyp margin and “loosening up” the submucosa [6]. Submucosal injection before CSP, also known as CS-EMR, has been reported in several studies. Recent studies reported that large colon polyps with an average size of 2 cm were successfully resected using CS-EMR without major adverse events [6,7,23]. The rate of residual or recurrent adenoma was reported as 0.6%–9.7% on follow-up colonoscopy within 1 year after CS-EMR, which is comparable to results of HSP [7,24]. However, most of these reports were studies on CS-EMR for large colorectal polyps measuring >1 cm. To the best of our knowledge, this is the first study to evaluate the effectiveness of submucosal injection in CSP for small polyps by comparing CSP and CS-EMR. In this study, no difference in the complete resection rate or the incidence of complications was observed between the CSP and CS-EMR groups, and the total procedure time was significantly increased with CS-EMR. These results suggest that submucosal injection is not helpful in CSP for small colorectal polyps.

In this study, the rate of immediate bleeding was 8% (8 cases), which is similar to that of previous studies [19]. Two patients (2.0%) had delayed bleeding; one of whom developed both immediate and delayed bleeding. He had been taking aspirin and warfarin for coronary artery disease and switched to heparin bridge therapy after the warfarin discontinuation because surgery was scheduled a week later. After the procedure, hemostasis was performed with clips for immediate bleeding. Delayed bleeding occurred at 3 days post-procedure. Colonoscopy showed an ulcer at the clip site with an adherent clot; therefore, additional clips were placed. Another patient with delayed bleeding was also safely treated with a hemoclip without transfusion. No patient had massive bleeding requiring surgery or transfusion, and all patients with bleeding were treatable with endoscopic procedures. No patients had colonic perforation.

This study analyzed the risk factors for PPB, including both immediate and delayed bleeding because only a small number (2) of patients developed delayed bleeding. Results showed that the risk of PPB increased with both warfarin (OR, 42.334; 95% CI, 1.006–1,781.758) and DOACs (OR, 35.244; 95% CI, 3.853–322.397). Warfarin is well known for increasing risk of procedure-related bleeding [25,26]. DOACs have been reported to be relatively safe compared to warfarin in terms of postpolypectomy bleeding [27,28]. Conversely, based on our results, a recent study reported that PPB risk was similar between patients taking warfarin and those taking DOACs [29]. Longer duration of anticoagulant use interruption prior to colonoscopy would possibly reduce bleeding risks associated with residual anticoagulant activity; however, this may expose patients to a higher risk of cardiovascular complications. Large-scale prospective studies will be needed to definitively answer remaining questions on the effects of DOACs on colonoscopy outcomes.

Polyp size was suspected to be a risk factor for PPB in univariate analysis (OR, 1.740; 95% CI, 1.060–2.858) but did not show statistically significant results in multivariate analysis. In previous studies, larger polyps (>1 cm) have been reported as risk factors for immediate and delayed PPB [30,31].

This study has several limitations. First because of the small number of study patients, the incidence of complications was insufficient to show a statistically significant difference. In addition, only two patients had delayed bleeding; therefore, risk factors for immediate and delayed bleeding could not be analyzed separately. If a study is conducted with a larger number of polyps in the future, whether submucosal injection will be clinically helpful in CSP for small colorectal polyps may be clarified.

Second, the evaluation of complete resection was confirmed only based on endoscopic gross findings. The muscularis mucosae (MM) is known to be only partially removed in cold snare polypectomy. If prior injection (CS-EMR) enables removal of the entire MM beneath the lesion and enables a negative vertical margin, the remnant/recurrence would be less frequent. If a histological examination was performed, more accurate results could be achieved. We washed the resection site after polypectomy with water and observed resection margins in detail. Only patients with clearly evident resection margin without remnant lesions were judged as complete resection, and the complete resection rate was 94%. A recent study reported a pathologic complete resection rate of 93.2% after CSP, which is similar to the results of our study [3].

Third, in patients taking antithrombotic agents, whether to discontinue or maintain the drugs was determined by evaluating the cardiovascular risk of each patient according to higher-risk endoscopic procedures. Patients who discontinued antithrombotics for several days before the procedure were also classified as taking antithrombotics. Therefore, the risk of bleeding from antithrombotic agents might have been evaluated as lower than the actual risk.

Patients were not randomized and those receiving submucosal injection had their procedures performed earlier than those who did not receive submucosal injection. Although no obvious statistical differences in the demographics were observed in the two groups and no other known technical changes in procedures occurred during the study period, we cannot exclude the effect of unknown biases.

Finally, the study was conducted at a Veteran’s hospital; therefore, majority of patients were men, and only 5% were women.

In conclusion, the effect of submucosal injection in cold snare polypectomy was not significant for small colorectal polyps. Anticoagulants such as warfarin and DOACs are risk factors for postpolypectomy bleeding, and patients taking these medications should be treated carefully to prevent postpolypectomy bleeding.

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