内镜黏膜切除术治疗大肠广基大息肉

目的探讨内镜黏膜切除术(EMR)对肠道广基大息肉样病变的治疗价值。方法采用结肠镜下大肠黏膜切除术治疗135例共157个结直肠广基大息肉。病灶黏膜下注射肾上腺素生理盐水后,一次圈套整块切除或分次圈套切除病变,回收全部标本送病理检查,术后结肠镜随访。结果全部息肉EMR一次切除,除3个位于直肠黏膜下的病灶小于1 cm外,其余均大于1.5 cm,最大的13 cm×12 cm,无手术并发症。术后病理:腺瘤123个,其中有异型增生80个;黏膜内癌11个;增生性息肉20个;直肠类癌3个。随访中,有2例大于7 cm的直肠腺瘤分别于术后1个月及3个月复查时复发,均给予热活检钳完整钳除,病理分别为增生性息肉和绒毛状腺瘤,再复查6-12个月无复发。结论EMR是治疗大肠癌前病变及黏膜内癌安全、有效的方法。     

Meta-analysis and systematic review of colorectal endoscopic mucosal resection

AIM： To evaluate the proportion of successful complete cure en-bloc resections of large colorectal polyps achieved by endoscopic mucosal resection （EMR）. METHODS： Studies using the EMR technique to resect large colorectal polyps were selected. Successful complete cure en-bloc resection was defined as one piece margin-free polyp resection. Articles were searched for in Medline, Pubmed, and the Cochrane Control Trial Registry, among other sources. RESULTS： An initial search identified 2620 reference articles, from which 429 relevant articles were selected and reviewed. Data was extracted from 25 studies （n = 5221） which met the inclusion criteria. All the studies used snares to perform EMR. Pooled proportion of en-bloc resections using a random effect model was 62.85% （95% CI： 51.50-73.52）. The pooled proportion for complete cure en-bloc resections using a random effect model was 58.66% （95% CI： 47.14-69.71）. With higher patient load （〉 200 patients）, this complete cure en-bloc resection rate improves from 44.19% （95% CI： 24.31-65.09） to 69.17% （95% CI： 51.11-84.61）. CONCLUSION： EMR is an effective technique for the resection of large colorectal polyps and offers an alternative to surgery.     

Difficult colorectal polypectomy: Technical tips and recent advances

Colonoscopy has been shown to be an effective modality to prevent colorectal cancer (CRC) development. CRC reduction is achieved by detecting and removing adenomas, which are precursors of CRC. Most colorectal polyps are small and do not pose a significant challenge for trained and skilled endoscopists. However, up to 15% of polyps are considered “difficult”, potentially causing life-threatening complications. A difficult polyp is defined as any polyp that is challenging for the endoscopist to remove owing to its size, shape, or location. Advanced polypectomy techniques and skills are required to resect difficult colorectal polyps. There were various polypectomy techniques for difficult polyps such as endoscopic mucosal resection (EMR), underwater EMR, Tip-in EMR, endoscopic submucosal dissection (ESD), or endoscopic full-thickness resection. The selection of the appropriate modality depends on the morphology and endoscopic diagnosis. Several technologies have been developed to aid endoscopists in performing safe and effective polypectomies, especially complex procedures such as ESD. These advances include video endoscopy system, equipment assisting in advanced polypectomy, and closure devices/techniques for complication management. Endoscopists should know how to use these devices and their availability in practice to enhance polypectomy performance. This review describes several useful strategies and tips for managing difficult colorectal polyps. We also propose the stepwise approach for difficult colorectal polyps.     

内镜下黏膜切除术治疗胃肠道息肉样病变的70例临床分析

目的 探讨内镜下黏膜切除术（ endoscopic mucosal resection,EMR） 在切除胃肠道息肉中的应用价值.方法 回顾性分析70例（82枚息肉）行EMR治疗胃肠道息肉的临床资料.结果 30例患者40枚胃息肉及40例患者42枚结肠息肉经EMR 治疗后,病变均完整切除,无出血、感染和穿孔等并发症发生.结论 EMR是临床上治疗胃肠道息肉的一种安全有效的内镜治疗手段,值得临床推广.     

阑尾腔内息肉内镜下治疗的初步观察

2016年1月—2020年12月间,在首都医科大学附属北京友谊医院消化内科行内镜下治疗的阑尾腔内息肉病例共6例,息肉直径0.3~1.3 cm。6例阑尾腔内息肉均顺利完成内镜下治疗,其中3例行内镜黏膜切除术整块切除、1例行内镜黏膜切除术分片切除、1例行内镜黏膜下剥离术切除、1例予活检钳冷钳除。6例术后均未出现出血、穿孔、感染和急性阑尾炎等并发症。3例术后复查创面愈合良好、无复发,其余3例暂未复查结肠镜。以上结果初步证实,阑尾腔内息肉行内镜下治疗安全和有效。     

EMR of large sessile colorectal polyps

BACKGROUND: EMR optimizes histopathologic assessment of resected lesions. This study evaluated the outcome of EMR of large sessile colorectal polyps in terms of complications and recurrence. METHODS: An uncontrolled prospective study was conducted of a cohort of 136 patients with sessile colorectal polyps referred for EMR. After submucosal injection, EMR was performed piecemeal by either snare polypectomy alone or with cap aspiration. RESULTS: In 136 patients, a total of 139 sessile polyps were resected, 86 of which were in the right colon. Median polyps diameter was 20 mm in the right colon and 30 mm in the other colonic segments. Intraprocedure bleeding occurred after 15 polypectomies (10.8%) and was controlled endoscopically in all cases; there was no delayed bleeding. Post-polypectomy syndrome occurred in 5 patients (3.7%). There was no perforation. Invasive carcinoma was found in 17 sessile colorectal polyps, and surgery was performed in 10 of 17 cases. Follow-up colonoscopy in 93 patients without invasive carcinoma (96 polyps), over a median of 12.3 months, disclosed local recurrence of 21 adenomatous polyps (21.9%). Colonoscopic follow-up in 5 of the 7 patients, who had sessile colorectal polyps with invasive carcinoma and did not undergo surgery, disclosed no local recurrence. CONCLUSIONS: EMR, including EMR with cap aspiration, is effective and safe for removal of sessile colorectal polyps throughout the colon.     

内镜下黏膜切除术治疗大肠平坦型病变30例

目的：探讨内镜下黏膜切除术（EMR）在大肠平坦型病变中的治疗价值。方法：对30例有大肠平坦型病变患者共36处病灶进行染色放大后行EMR治疗,评价其治疗效果和并发症。结果：36处病灶最大直径0．8～2．5cm（平均1．4±0．5cm）,32处一次性完整切除,4处分块切除;3例出现术中出血,经氩气凝固术（APC）及电凝治疗后止血,1例出现术后迟发性出血,经金属夹治疗后止血。30例患者术后1月复查肠镜,创面愈合,术后随访6～12月（平均9．3月）,未见病变复发及残留。结论：EMR能有效治疗大肠平坦型病变,方法简便易行,创伤小,安全有效,值得临床推广。

Abstract：

Objective： To study the value of endoscopic mucosal resection （EMR） for flat-type colorectal polyps. Methods： Thirty-six lesions in 30 patients with flat-type colorectal polyps were resected by EMR after magnifying endoscope and mucosa staining, and the therapeutic effects and adverse reactions were evaluated. Results： The maximum diameter of 36 lesions was 0. 8-2. 5 cm （mean 1.4 ± 0. 5 cm） ,32 lesions of which were onetime complete resection and four lesions were piece EMR. Bleeding occurred in 3 cases, and the Argon Plasma Coagulation （APC） and electrocoagulation were taken to stop bleeding, 1 case of delayed postoperative bleeding,metal clips was used to stop bleeding after treatment. The colonoscopy after a month in 30 patients showed wound healing, no recurrence and residual lesions were found in these patients followed up for 6- 12 months （average 9. 3 months）. Conclusions： Colorectal flat-type polyps can be effectively treated by EMR, and the method is simple, less traumatic, but safe and worthy to be popularized.     

Endoscopic mucosal resection in the upper gastrointestinal tract

Endoscopic mucosal resection （EMR） is a technique used to locally excise lesions confined to the mucosa. Its main role is the treatment of advanced dysplasia and early gastrointestinal cancers. EMR was originally described as a therapy for early gastric cancer. Recently its use has expanded as a therapeutic option for ampullary masses, colorectal cancer, and large colorectal polyps. In the Western world, the predominant indication for EMR in the upper gastrointestinal tract is the staging and treatment of advance dysplasia and early neoplasia in Barrett＇s esophagus. This review will describe the basis, indications, techniques, and complications of EMR, and its role in the management of Barrett＇s esophagus.     

Large endoscopic mucosal resection for colorectal tumors exceeding 4 cm

AIM:To evaluate the feasibility and the outcome of endoscopic mucosal resection(EMR)for large colorectal tumors exceeding 4 cm(LCRT)undergoing piecemeal resection. METHODS:From January 2005 to April 2008,146 digestive tumors larger than 2 cm were removed with the EMR technique in our department.Of these,34 tumors were larger than 4 cm and piecemeal resection was carried out on 26 colorectal tumors.The mean age of the patients was 71 years.The mean follow-up duration was 12 mo. RESULTS:LCRTs were located in ...     

What can be the criteria of outpatient-based endoscopic resection for colon polyp?

AIM: To investigate whether out-patient based endo-scopic mucosal resection(EMR) for colon polyps ≤ 10 mm is safe.METHODS: Between January 2004 and December 2012, a total of 3015 EMR cases conducted in 1320 patients were retrospectively reviewed. The factors contributing delayed hemorrhage were analyzed. We calculated the probability of delayed bleeding after stratifying conditions of specific risk factors.RESULTS: The size of the polyp(95%CI: 1.096-1.164, P 0.001) and patients with chronic renal failure(95%CI: 1.856-45.106, P = 0.007) were identified as independent risk factors for delayed bleeding in multi-variate analysis. 95%CI for percent of delayed bleedingaccording to polyp size was determined for the fol-lowing conditions: size ≤ 10 mm, 0.05%-0.43%; 20 mm ≥ size 10 mm, 0.54%-2.08%; size 20 mm, 4.22%-11.41%. 95%CI was determined for the risk of serious immediate bleeding for a polyp ≤ 10 mm was 0.10%-0.56%. Finally, 95%CI for percent of incomplete resection was 0.07%-0.49% in polyps ≤ 10 mm. CONCLUSION: It seems acceptable to perform outpa-tient-based EMR for colon polyps ≤ 10 mm.     

Endoscopic resection techniques for colorectal neoplasia:Current developments

Endoscopic polypectomy and endoscopic mucosal resection(EMR) are the established treatment standards for colorectal polyps. Current research aims at the reduction of both complication and recurrence rates as well as on shortening procedure times. Cold snare resection is the emerging standard for the treatment of smaller(< 5 mm) polyps and is possibly also suitable for the removal of noncancerous polyps up to 9 mm. The method avoids thermal damage, has reduced procedure times and probably also a lower risk for delayed bleeding. On the other end of the treatment spectrum, endoscopic submucosal dissection(ESD)offers en bloc resection of larger flat or sessile lesions. The technique has obvious advantages in the treatment of high-grade dysplasia and early cancer. Due to its minimal recurrence rate, it may also be an alternative to fractionated EMR of larger flat or sessile lesions. However, ESD is technically demanding and burdened by longer procedure times and higher costs. It should therefore be restricted to lesions suspicious for high-grade dysplasia or early invasive cancer.The latest addition to endoscopic resection techniques is endoscopic fullthickness resection with specifically developed devices for flexible endoscopy.This method is very useful for the treatment of smaller difficult-to-resect lesions,e.g., recurrence with scar formation after previous endoscopic resections.     

Endoscopic mucosal resection of large hyperplastic polyps in 3 patients with Barrett＇s esophagus

AIM: To report the endoscopic treatment of large hyperplastic polyps of the esophagus and esophago-gastric junction (EGJ) associated with Barrett's esophagus (BE) with low-grade dysplasia (LGD), by endoscopic mucosal resection (EMR). METHODS: Cap fitted EMR (EMR-C) was performed in 3 patients with hyperplastic-inflammatory polyps (HIPs) and BE. RESULTS: The polyps were successfully removed in the 3 patients. In two patients, with short segment BE (SSBE) (<= 3 cm), the metaplastic tissue was completely excised. A 2 cm circumferential EMR was performed in one patient with a polyp involving the whole EGJ. A simultaneous EMR-C of a BE-associated polypoid dysplastic lesion measuring 1 cm multiply 10 cm, was also carried out. In the two patients, histologic assessment detected LGD in BE. No complications occurred. Complete neosquamous re-epithelialization occurred in the two patients with SSBE. An esophageal recurrence occurred in the remaining one and was successfully retreated by EMR. CONCLUSION: EMR-C appears to be a safe and effective method for treating benign esophageal mucosal lesions, allowing also the complete removal of SSBE.     

内镜下黏膜切除术治疗消化道肿瘤

目的 探讨内镜下黏膜切除术(EMR)对消化道肿瘤的治疗价值。方法 利用染色、放大内镜及超声内镜探测病变范围及侵犯深度,对位于黏膜层及黏膜肌层的早期癌、癌前病变、黏膜下肿瘤、侧向发育型息肉、无蒂或亚蒂巨大息肉、息肉癌变等病变行EMR治疗。结果 病灶最大直径6cm。2例早期食管癌、1例早期贲门癌、1例早期大肠癌及2例胃中、重度异型增生经EMR及透明帽负压吸引EMR切除,观察3-18个月无复发;31例黏膜下肿瘤经EMR和透明帽负压吸引EMR,均完全切除;对13例侧向发育型息肉及21例亚蒂和无蒂大息肉及局部癌变息肉采用EMR或分片黏膜切除术切除。术中出血5例,出血率7.04％,经内镜治疗停止。1例4.5 cm腺瘤术后3个月复发。结论 在超声内镜、色素内镜及放大内镜的指导下,采用内镜下黏膜切除术治疗部分消化道早期癌、癌前病变、侧向发育型及无蒂或亚蒂臣大息肉、局部癌变息肉及黏膜肌层的肿瘤,足一项安全有效的内镜治疗疗法。     

Efficacy and safety of three different endoscopic methods in treatment of 6–20 mm colorectal polyps

Abstract

Objective: Endoscopic resection of colorectal polyps is widely established as the optimal method to manage precancerous lesions. But the optimal technique for removal of the polyps is uncertain. The aim of this study was to compare the efficacy and safety of three methods for the management of 6–20mm colorectal polyps.

Methods: A prospective, randomised controlled trial was conducted at the 900TH Hospital of Joint Logistics Support Force in Fujian, China. Endoscopically diagnosed colorectal polyps, 6–20 mm in size, were randomly assigned to the cold snare polypectomy (CSP), cold snare endoscopic mucosal resection (CS-EMR) or endoscopic mucosal resection (EMR) group. After polypectomy, additional 3–5 forceps biopsies by leading narrow-band imaging (NBI) were performed at the base and margins of polypectomy sites to assess the presence of residual polyp tissue and all samples were sent for histopathological analysis to assess completeness of resection. Polypectomy timing, tissue retrieval and complications were recorded at the time of the procedure.

Results: A total of 781 polyps in 404 patients were assessed and randomly assigned to each group. Of these, 763 polyps were finally analyzed based on the pathology results. The complete resection rates with CSP, CS-EMR and EMR were 81.6%, 94.1% and 95.5%, respectively (p?<?.001). The intraprocedural bleeding rate, immediately after polypectomy, was significantly higher in the CSP group than in the CS-EMR and EMR group (9.4% vs. 4.4% vs. 1.9%; p?<?.001). However,delayed bleeding was higher in the EMR group than in the CSP and CS-EMR group (2.6% vs. 1.2% vs. 0.8%, respectively; p?=?.215). In the multivariate analysis showed that the operation method, lesion size, morphology and the number of resection were independent risk factors for complete resection rate (CRR) (p < .05), but the location and pathological classification of polyps had no significant influence on CRR.

Conclusions: CS-EMR is safe and effective in the treatment of 6–20?mm colorectal polyps. Especially for 6–15?mm non-pedunculated polyps, CS-EMR has a high histological complete resection rate comparable to EMR, and retains the low risk of delayed complications after polypectomy with cold snare. CS-EMR is expected to become a more valuable new cold-cutting technique after cold snare polypectomy.     

内镜下黏膜切除术治疗老年及老年前期胃肠道息肉的临床研究

目的探讨内镜下黏膜切除术（endoscopic mucosal resection,EMR）对老年及老年前期胃及大肠息肉的治疗效果,并对其临床病理特征、适应证、并发症等进行讨论。方法 2003年10月至2009年10月共完成老年及非老年胃息肉及大肠息肉EMR手术1076例;对切除标本进行病理检查,记录术中及术后发生的并发症及处理情况,术后定期内镜随访1-60月。结果 348处胃息肉经首次或再次EMR治疗病变均完整清除,病理示炎性息肉、增生性息肉、腺瘤性息肉分别占62.6%（218/348）,27.9%（97/348）,9.5%（33/348）。935处大肠息肉中892处病变经首次或再次EMR治疗病变完整清除,治愈率为95.4%;23处病变（2.5%）术后病理示浸润癌再追加外科开腹手术。病理示炎性息肉、增生性息肉、腺瘤性息肉、腺瘤癌变分别占29.1%（272/935）,20.9%（195/935）,46.2%（432/935）,3.9%（36/935）,随年龄的增加,腺瘤性息肉的比例逐渐升高（P〈0.01）。术中出血52例（4.8%）,均内镜下止血;术后迟发出血（〉24 h）21例（2.0%）,其中15例经内镜下止血,6例经输血及内科保守治疗后止血。无穿孔、感染等并发症发生。随访期间所有病例均无复发。结论 EMR是一种安全和微创的内镜治疗手段,对老年及老年前期胃及大肠息肉治疗的疗效优于传统的内镜下治疗方法。     

麻醉肠镜在老年患者大肠息肉黏膜切除术中的应用

目的探讨麻醉肠镜在老年患者大肠息肉行黏膜切除术(endoscopic mucosal resection,EMR)中的临床应用价值。方法将306例肠镜下发现大肠息肉的老年患者随机分为两组:麻醉肠镜组(156例);使用异丙酚和芬太尼行静脉麻醉;普通肠镜组(150例):仅给予肠道准备。观察两组患者EMR术前、中、后的血压[包括舒张压(SBP)、收缩压(DBP)]、心率(HR)、末梢血氧饱和度(Sp O2)和两组患者术中反应、并发症、手术操作时间及患者满意度。结果术中麻醉肠镜组SBP、DBP、HR均明显低于普通肠镜组(P均0.05),Sp O2无显著差异(P0.05);术前及术后两组患者SBP、DBP、HR、Sp O2均无显著性差异(P均0.05)。麻醉肠镜组患者满意度高。麻醉组手术操作时间(18.1±6.3)min,普通组(24.4±8.5)min,两组比较,差异有统计学意义(P0.05)。结论麻醉肠镜下对老年患者大肠息肉行EMR能够缩短操作时间,提高成功率,提高患者满意度,是一种治疗老年患者大肠息肉的简单、安全、有效的方法。     

Comparative efficacy and safety of resection techniques for treating 6 to 20mm,nonpedunculated colorectal polyps: A systematic review and network meta-analysis

IntroductionVarious endoscopic resection techniques have been proposed for the treatment of nonpedunculated colorectal polyps sized 6–20 mm, however the optimal technique still remains unclear.MethodsA comprehensive literature review was conducted for randomized controlled trials (RCTs), investigating the efficacy of endoscopic treatments for the management of 6–20 mm nonpedunculated colorectal polyps. Primary outcomes were complete and en bloc resection rates and adverse event rate was the secondary. Effect size on outcomes is presented as risk ratio (RR; 95% confidence interval [CI]).ResultsFourteen RCTs (5219 polypectomies) were included. Endoscopic mucosal resection(EMR) significantly outperformed cold snare polypectomy(CSP) in terms of complete [(RR 95%CI): 1.04(1.00–1.07)] and en bloc resection rate [RR:1.12(1.04–1.21)]. EMR was superior to hot snare polypectomy (HSP) [RR:1.04(1.00–1.08)] regarding complete resection, while underwater EMR (U-EMR) achieved significantly higher rate of en bloc resection compared to CSP [RR:1.15(1.01–1.30)]. EMR yielded the highest ranking for complete resection(SUCRA-score 0.81), followed by cold-snare EMR(CS-EMR,SUCRA-score 0.76). None of the modalities was different regarding adverse event rate compared to CSP, however EMR and CS-EMR resulted in fewer adverse events compared to HSP [RR:0.44(0.26–0.77) and 0.43(0.21–0.87),respectively].ConclusionEMR achieved the highest performance in resecting 6–20 mm nonpedunculated colorectal polyps, with this effect being consistent for polyps 6–9 and ≥10 mm; findings supported by very low quality of evidence.     

Nonampullary duodenal adenoma:Current understanding of its diagnosis,pathogenesis,and clinical management

Nonampullary duodenal adenomas are relatively common in familial adenomatous polyposis(FAP), but nonampullary sporadic duodenal adenomas(SDAs)are rare. Emerging evidence shows that duodenal adenomas, regardless of their anatomic location and whether they are sporadic or FAP-related, share morphologic and molecular features with colorectal adenomas. The available data suggest that duodenal adenomas develop to duodenal adenocarcinomas via similar mechanisms. The optimal approach for management of duodenal adenomas remains to be determined. The techniques for endoscopic resection of duodenal adenoma include snare polypectomy, endoscopic mucosal resection(EMR), endoscopic submucosal dissection(ESD), and argon plasma coagulation ablation. EMR may facilitate removal of large duodenal polyps. Although several studies have reported cases of successful ESD for duodenal adenomas, the procedure is technically difficult to perform safely because of the anatomical properties of the duodenum. Although current clinical practice recommends endoscopic resection of all large duodenal adenomas in patients with FAP, endoscopic treatment is usually insufficient to guarantee a polypfree duodenum. Surgery is indicated for FAP patients with severe polyposis or nonampullary SDAs or FAPrelated polyps not amenable to endoscopic resection. Further studies are needed to develop newer endoscopic techniques to guide diagnostic and therapeutic decisions for future management of nonampullary duodenal adenomas.     

Endoscopic mucosal resection of 161 cases of large sessile or flat colorectal polyps

OBJECTIVE: Large sessile or flat colorectal polyps, which are traditionally treated surgically, may be amenable to endoscopic mucosal resection (EMR), often using a piecemeal method. Appropriate selection of lesions and a careful technique may enhance the efficacy of EMR for polyps >or=20 mm in diameter without compromising safety. The aim of this study was to identify the factors that may be predictive of the risk of polyp recurrence. MATERIAL AND METHODS: A retrospective analysis was conducted on the outcome of 161 polyps >or=20 mm in diameter, treated by piecemeal EMR at a single centre using the "lift and cut" technique. All records were reviewed for polyp size, site, morphology and histology. Polypectomy technique, patient follow-up, polyp recurrence and surgical interventions were also recorded. RESULTS: Over an 8-year period, 161 colonic polyps measuring >or=20 mm were removed by EMR. Follow-up data were available for 149 cases (93%) with a mean polyp diameter of 32.5 mm; the total success rate of endoscopic polyp removal was 95.4%. The number of cases requiring 1, 2, 3, 4 and 6 attempts at EMR was 89 (60%), 36 (24%), 14 (9%), 2 (1.3%) and 1 (0.7%), respectively. Recurrence was significantly related to polyp size (p<0.001). There was no statistically significant relationship between site and recurrence. Seven patients (4.6%) underwent surgical intervention after EMR because of failed clearance. There were no post-EMR perforations and significant bleeding was reported in only two patients (1.7%). CONCLUSIONS: With careful attention to technique, piecemeal EMR is a safe option for the resection of most sessile and flat colorectal polyps >or=20 mm in size. A stricter follow-up may be required for larger lesions because of a higher risk of recurrence.     

Abdominal pain post endoscopic mucosal resection: Treat the patient not the CT scan

An 85-year-old female, with hereditary nonpolyposis colorectal cancer syndrome, underwent a colonoscopy and endoscopic mucosal resection(EMR) of a 25-mm proximal ascending colon polyp(Paris classification 0-Is). Post-procedure, the patient developed abdominal pain in the right iliac fossa which settled 1 h later. An urgent computed tomography(CT) scan of her abdomen was organised which happened 6 h post onset of abdominal pain. She had radiological evidence of perforation on the CT scan but clinically remained well and was managed conservatively. The exact aetiology of this patient’s symptoms is not known. We suspect the radiological findings are probably due to a combination of injectate within the colonic wall and leakage of insufflated air or CO2 following transmural passage of the EMR needle. As EMR is becoming an increasingly effective treatment modality in the management of large sessile polyps, clinicians need to be aware of potential complications of treatment. It is also important to recognise that radiological features of perforation can be seen post EMR in the absence of an EMR associated perforation.