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Shichijo et al. Mini-invasive Surg 2022;6:19  https://dx.doi.org/10.20517/2574-1225.2021.121  Page 7 of 13

               However, preventive coagulation of visible vessels after colorectal ESD is not common when considering the
               risk of delayed perforation and post-ESD coagulation syndrome because of the thinness of the colon wall. A
               meta-analysis of eight studies concluded that prophylactic endoscopic closure might reduce the incidence of
                                        [64]
               delayed bleeding (5.2%-0.9%) .

               Perforation
               Intraprocedural perforations can usually be closed using endoclips and managed conservatively without
               surgical intervention when closed completely [65-67] , whereas delayed perforation may lead to peritonitis and
               require emergency surgery. Delayed perforation usually occurs within 48 h following ESD and presents with
               fever and severe abdominal pain. Considering the presence of free air on computed tomography (CT)
               images, consultation with surgeons for the indication of surgery is mandatory. We reported that about half
               of the cases of delayed perforation can be managed conservatively with fasting and antibiotics, whereas the
                                               [68]
               other half require emergency surgery . Recently, feasibility of endoscopic closure for delayed perforation
               using clips, endoloop, over-the-scope clip (OTSC; Ovesco, Tübingen, Germany), and polyglycolic acid sheet
               has been reported [69-71] .


               Here, we present a case of delayed perforation that was managed with OTSC. A 46-year-old woman with a
               laterally spreading tumor in the transverse colon was referred to our hospital. Colonoscopy at our
               institution revealed a 25-mm-sized non-granular type laterally spreading tumor without apparent signs of
               invasion [Figure 4A]. The lesion was removed en bloc by ESD in 33 min [Figure 4B] without muscle injury
               and prophylactic closure of the wound [Figure 4C]. The patient complained of severe abdominal pain 35 h
               following ESD; subsequently, a fever of 38.6 °C was recorded. CT revealed extraluminal air and increased fat
               concentration [Figure 4D]; therefore, delayed perforation was diagnosed, and antibiotics (tazobactam
               piperacillin hydrate) were initiated. The abdominal pain was localized, suggesting local peritonitis; hence,
               we decided to examine the ESD wound with colonoscopy using carbon dioxide insufflation.


               Colonoscopy 43 h after ESD revealed a 3-mm hole at the base of the ESD wound [Figure 5A]. Once we
               withdrew the colonoscope, after attaching an over-the-scope clip (OTSC, 11/6t) at the tip of the
               colonoscope, we re-approached the perforation site. Subsequently, the OTSC was placed after suctioning the
               perforation site and the surrounding tissue [Figure 5B]. A contrast agent was sprayed through the working
               channel of the colonoscope, and a CT scan showed no extraluminal leakage of the contrast medium, abscess
               formation, or ascites. Although laboratory tests the day after closure showed a peak C-reactive protein level
               of 31.2 mg/dL, her abdominal pain resolved gradually. Oral intake commenced on day 7 post-ESD, and she
               was discharged on day 8.

               Post ESD coagulation syndrome
               Even without definitive evidence of perforation on imaging, PECS sometimes occurs after colorectal ESD.
               Its incidence is 4.8%-40.2% [72-77] , and PECS leads to deviation from the clinical path and a longer
               hospitalization period, although PECS can be managed conservatively with antibiotics and fasting. Known
               risk factors for PECS are female sex [72-74] , proximal location of the lesion (cecum [73,74] , cecum or ascending
                                                    [76]
                    [72]
                                                                           [74]
               colon , and cecum to descending colon ), larger size [72,76] , fibrosis , and piecemeal resection . Lee
                                                                                                    [76]
               et al.  reported that prophylactic antibiotics reduced the incidence of PECS in a single-center randomized
                   [77]
               controlled trial. The study was performed at a single center, and the sample size was relatively small;
               therefore, we conducted a multicenter randomized controlled trial to examine the efficacy of perioperative
               antibiotics for the incidence of PECS (PPAP trial, performance of perioperative antibiotics for PECS) . A
                                                                                                      [78]
               prospective, multicenter, randomized controlled, parallel superiority trial was completed at 21 Japanese
               tertiary institutions. Patients with superficial colorectal lesions ≥ 20 mm and those who were planned ESD
               for a single lesion were eligible. Patients with perforation during or after ESD were excluded. Before the ESD
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