Int J Colorectal Dis DOI 10.1007/s00384-014-1901-3
ORIGINAL ARTICLE
Risk factors for delayed bleeding after endoscopic submucosal dissection for colorectal neoplasms Motomi Terasaki & Shinji Tanaka & Kenjiro Shigita & Naoki Asayama & Soki Nishiyama & Nana Hayashi & Koichi Nakadoi & Shiro Oka & Kazuaki Chayama
Accepted: 2 May 2014 # Springer-Verlag Berlin Heidelberg 2014
Abstract Purpose Although delayed bleeding is a major complication of endoscopic submucosal dissection (ESD) for colorectal neoplasms, few reports have assessed the risk factors for delayed bleeding after colorectal ESD. Methods This study included 363 consecutive patients in whom 377 colorectal neoplasms were resected using ESD between April 2006 and August 2012. We classified patients and lesions into two groups on the basis of presence or absence of delayed bleeding and retrospectively compared the clinicopathological characteristics and clinical outcomes of ESD between the two groups. Results Delayed bleeding occurred in 25 (6.6 %) of 377 lesions, and all cases of delayed bleeding were successfully controlled by endoscopic procedures. With respect to patientrelated factors, there was no significant difference between the groups in mean age, sex ratio, and current use of antithrombotic agents. With respect to lesion-related factors, there was no significant difference between the groups in mean lesion size, growth pattern, and mean procedure time (p=0.6). Lesions located in the rectum (vs colon, p=0.0005) and lesions with severe submucosal fibrosis (vs no or mild fibrosis, p=0.022) were significantly related to delayed bleeding. Upon multivariate analysis, lesions located in the rectum (vs colon, odds ratio 4.19; p=0.0009) were significantly related to delayed bleeding after colorectal ESD. M. Terasaki : K. Shigita : N. Asayama : S. Nishiyama : N. Hayashi : K. Nakadoi : K. Chayama Department of Gastroenterology and Metabolism, Hiroshima University Graduate School of Biomedical Sciences, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan S. Tanaka (*) : S. Oka Department of Endoscopy, Hiroshima University Hospital, Hiroshima, Japan e-mail:
[email protected]
Conclusions This study demonstrated that location of lesions in the rectum was a significant independent risk factor for delayed bleeding after ESD for colorectal neoplasms. Keywords Colorectal neoplasm . Endoscopic submucosal dissection . Delayed bleeding . Submucosal fibrosis
Introduction Endoscopic submucosal dissection (ESD) has been widely performed as curative treatment for early esophageal cancer and early gastric cancer [1–3] and for colorectal neoplasms in recent years [4–11]. However, when performing ESD for colorectal lesions, the intestinal wall is thin and the endoscope is difficult to manipulate; therefore, colorectal ESD should be performed by experienced endoscopists [9, 10]. Since April 2012, colorectal ESD has been approved for health insurance coverage in Japan, and the number of colorectal ESD procedures is expected to increase per institution. Therefore, the assessment and prediction of risks of complications provide important and useful information before colorectal ESD. The main complications of colorectal ESD are intestinal perforation and delayed bleeding. Some studies have assessed the risk factors for perforation during colorectal ESD [12–14]; however, few studies have assessed the risk factors for delayed postoperative bleeding. In this study, we aimed to clarify the risk factors for delayed bleeding after colorectal ESD.
Patients and methods Patients We introduced ESD for colorectal neoplasms in November 2002 and have performed 550 colorectal ESD procedures thus
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far at Hiroshima University Hospital. In this study, after full establishment of the ESD procedure, we examined consecutive ESD cases in 363 patients with 377 lesions treated between April 2006 and August 2012, after excluding nine patients with nine lesions that were abandoned. The indications for ESD in our hospital were identical to those reported previously (Table 1) [4, 5, 15]. Before ESD, we examined all lesions primarily by magnifying endoscopy [16–20] and determined the indications for ESD in accordance with the indications given in Table 1. The study protocol was approved by the ethics committee of Hiroshima University Hospital, and written informed consent was obtained from all patients. ESD procedures The ESD procedures were performed by an endoscopic specialist (S.T.). We primarily used a Dual knife (Olympus Medical Systems Co., Ltd, Tokyo, Japan) or Flex knife (Olympus Medical Systems Co., Ltd); depending on the situation, we also used a Hook knife (Olympus Medical Systems Co., Ltd) and/or an SB knife Jr. (Sumitomo Bakelite Co., Ltd, Tokyo, Japan). Carbon dioxide (CO2) insufflation was used instead of room air insufflation. ESD procedures were performed using a high-resolution magnifying video endoscope (CF-H260AZI or CF-Q260JI; Olympus Optical Co., Ltd, Tokyo, Japan) or upper gastrointestinal endoscope (GIFQ260J; Olympus Optical Co., Ltd.). For the injection solution, we used a mixture with a 1:1 ratio of 0.4 % sodium hyaluronate (MucoUp R ; Johnson & Johnson, New Brunswick, NJ, USA) and 10 % glycerin solution, plus a small
Table 1 Indications for colorectal endoscopic submucosal dissection (ESD) (1) Large (>20 mm in diameter) lesions for which endoscopic treatment is indicated but for which en bloc resection by snare endoscopic mucosal resection EMR would be difficult LST of nongranular type (LST-NG), particularly the pseudo-depressed type Lesions showing a type VI pit pattern Cancer with submucosal infiltration Large depressed type tumor Large lesions of the protruded type suspected to be carcinoma* (2) Mucosal lesions with fibrosis caused by prolapse due to biopsy or peristalsis of the lesions** (3) Local residual early cancer after endoscopic resection (4) Sporadic localized tumors in chronic inflammation such as ulcerative colitis * Including an LST-G consisting of large nodules ** Caused by biopsy or peristalsis of lesion (prolapse) LST-NG laterally spreading tumor of the nongranular type, LST-G laterally spreading tumor of the granular type
amount of indigo carmine (indigo carmine/Muco UpR + glycerin: 0.2/20 mL). Histologic assessment The excised specimens were stretched and pinned on the flat board, fixed in 10 % buffered formalin, sliced into 2-mm sections, and assessed microscopically. Histopathologic diagnosis was performed according to the WHO classification system [21]. The depth of submucosal invasion was determined according to the General Rules for Clinical and Pathological Studies on Cancer of the Colon, Rectum, and Anus outlined by the Japanese Society for the Colon and Rectum (JSCCR) [22], and lesions were classified as adenoma (including tubular adenoma, tubulovillous adenoma, and serrated adenoma), carcinoma in situ (Ca-M), and adenocarcinoma with submucosal invasion (Ca-SM). Identification of risk factors for delayed bleeding after ESD In this study, delayed bleeding was defined according to the criteria reported by Tajiri et al. [23]. To identify risk factors for delayed bleeding after ESD, we compared patient-related factors, i.e., age, sex, and use of antithrombotic agents, and lesion-related factors, i.e., lesion size, location, growth pattern, histopathology, submucosal fibrosis, and procedure time. Tumor locations were in the colon and rectum. Lesions located in the rectum were grouped according to their location in the upper rectum (Ra) or the lower rectum (Rb). Based on their growth patterns, the tumors were classified into either polypoid tumors or laterally spreading tumors (LSTs). LSTs were further divided into granular type (LST-G) and nongranular type (LST-NG) [24]. According to the degree of submucosal fibrosis, tumors were divided into three groups: F0, F1, and F2, as described previously [12], which were further subdivided into two groups: F0 or F1 and F2. In this study, we classified delayed bleedings after ESD into early delayed bleeding (within 48 h after ESD) and late delayed bleeding (later than 48 h after ESD). Statistical analysis Values are shown as median with range or mean ± SD. Differences among continuous variables were analyzed by the Kruskal–Wallis H test, and differences among nominal variables were analyzed by the chi-square test with Yates’ modification. Multivariate analysis with logistic regression was used to identify risk factors for delayed bleeding. Odds ratios were calculated to estimate the relative risk of delayed bleeding when various factors were present. Analyses were performed using JMP statistical software version 9.02 (SAS Institute, Cary, NC, USA). A p value less than 0.05 was considered statistically significant.
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Results The mean age of 363 patients was 66.9±11.2 years, and the mean size of 377 lesions was 35.1±18.7 mm. Of the total 377 lesions, delayed bleeding occurred in 25 lesions (6.6 %). The mean number of days from ESD to onset of bleeding was 2.8± 3.1 days (range, 0–12 days), and the mean decrease in hemoglobin was 0.5±0.9 g/dL (range, 0–3.4 g/dL). No patients had hemorrhagic shock resulting from delayed bleeding, and no blood transfusions were required. All cases of delayed bleeding were successfully treated by endoscopic hemostasis involving clipping and/or hemostatic forceps, without surgical intervention.
bleeding was significantly higher (17/25; 68 %) than that of no delayed bleeding (111/352; 21.5 %) (p=0.0005). The rate of lesions with severe fibrosis (F2) with delayed bleeding (12/25; 48 %) was significantly higher (p=0.022) than that of lesions without bleeding (88/352; 25 %). The lesions located in the rectum and with those located in the colon are further detailed: lesion size was significantly greater (32.9 vs 40.0 mm; p=0.002), the rate of LST-G was significantly higher (35.3 vs 62.5 %; p
