PRESENT STATUS and PERSPECTIVES OF SUBMUCOSAL DISSECTING METHOD OF ENDOSCOPIC MUCOSAL RESECTION IN THE COLORECTUM IN JAPAN

Endoscopic mucosal resection (EMR) is one of the endoscopic procedures for treatment of intramucosal cancer of the gastrointestinal tract. This method enables complete resection of a lesion, however, the size of lesions which can be resected en bloc has a limit. For lesions which can not be resected en bloc, endoscopic piecemeal mucosal resection (EPMR) are employed. However, it is often difficult to determine cancer invasion at holizontal and vertical cut end on pathological examination of resected specimens. Therefore, for the purpose of en bloc resection submucosal dissecting method of endoscopic mucosal resection (SDEMR) that is a method by which mucosa is dissected using some special devices after circumferential mucosal incision around the lesion was proposed. It enables us to resect large lesions which cannot be removed en bloc by EMR. Therefore, it is possible that this procedure is able to prevent residual cancer. Furthermore, sufficient pathological examination of resected specimens is possible, and it helps to determine a therapeutic plan after resection. It is now widely accepted as one of the endoscopic procedures for treatment of early gastric cancer, however, there have been few reports on its experience in the colorectum. Then, in order to consider the perspectives of SDEMR in the colorectum, the present status of it in Japan in August 2003 was analyzed and reviewed in this paper.     

ENDOSCOPIC SUBMUCOSAL DISSECTION FOR RECURRENT GASTRIC TUMORS

Endoscopic resection has been accepted as the standard treatment for intramucosal gastric tumors of differentiated type. However, the indication was limited to small tumors to achieve en bloc resection and prevent local recurrence in cases of conventional endoscopic mucosal resection (EMR) such as the strip biopsy and the cap technique. To avoid multi‐fragmental resection, we have developed endoscopic submucosal dissection (ESD) as a new endoscopic resection technique. ESD is a remarkable technique, because we make it possible to remove the lesions en bloc regardless of size, shape, coexisting ulcer, and location. However, it is difficult or impossible to resect recurrent tumors en bloc in conventional EMR owing to hard fibrosis, and some patients need laparotomy. Using ESD, we can dissect the submucosal layer as we directly look at the submucosa, and remove the lesion safely and reliably even in cases of hard fibrosis. The key to treatment of recurrent tumors in ESD are as follows: (i) using enough submucosal injection solution (we use a mixture of Glyceol and 1% 1900 kDa hyaluronic acid preparation); (ii) incising the mucosa without fibrosis; (iii) understanding characteristics of various cutting devices, and changing other devices in difficult situations. In these ways we can remove the majority of the recurrent tumors en bloc. Hence, we consider that ESD is a very effective treatment which achieves excellent en bloc and complete resection rates and enables patients with intramucosal gastric tumors to a recurrent‐free survival even in recurrent tumors.     

Colorectal endoscopic submucosal dissection: present status and future perspective,including its differentiation from endoscopic mucosal resection

Endoscopic submucosal dissection (ESD) allows en bloc resection of a lesion, irrespective of the size of the lesion. ESD has been established as a standard method for the endoscopic ablation of malignant tumors in the upper gastrointestinal (GI) tract in Japan. Although the use of ESD for colorectal lesions has been studied via clinical research, ESD is not yet established as a standard therapeutic method for colorectal lesions because colorectal carcinoma has unique pathological, organ specific characteristics that differ radically from those of the esophagus and stomach, and scope handling and control is more difficult in the colorectum than in the upper GI tract. Depending on the efficacy of endoscopic mucosal resection (EMR) and the clinicopathological characteristics of the colorectal tumor, the proposed indications for colorectal ESD are as follows: (1) lesions difficult to remove en bloc with a snare EMR, such as nongranular laterally spreading tumors (particularly the pseudo depressed type), lesions showing a type VI: pit pattern, and large lesions of the protruded type suspected to be carcinoma; (2) lesions with fibrosis due to biopsy or peristasis; (3) sporadic localized lesions in chronic inflammation such as ulcerative colitis; and (4) local residual carcinoma after EMR. Colorectal ESD is currently in the development stage, and a standard protocol will be available in the near future. We hope that colorectal tumors will be efficiently treated by a treatment method appropriately selected from among EMR, ESD, and surgical resection after precise preoperative diagnosis based on techniques such as magnifying colonoscopy.     

Matched case-control study comparing endoscopic submucosal dissection and endoscopic mucosal resection for colorectal tumors

Background and Aim: For large colorectal tumors, the en bloc resection rate achieved by endoscopic mucosal resection (EMR) is insufficient, and this leads to a high rate of local recurrence. As endoscopic submucosal dissection (ESD) has been reported to achieve a higher rate of en bloc resection and a lower rate of local recurrence in the short‐term, it is expected to overcome the limitations of EMR. We conducted a matched case‐control study between ESD and EMR to clarify the effectiveness of ESD for colorectal tumors. Methods: Between April 2005 and February 2009, a total of 28 colorectal tumors in 28 patients were resected by ESD and were followed up by colonoscopy at least once. As a control group, 56 EMR cases from our prospectively completed database were matched. En bloc resection, complication and recurrence rates were compared between the two groups. Results: The mean sizes of the lesions were 27.1 mm in the ESD group and 25.0 mm in the EMR group. The en bloc resection rate was significantly higher in the ESD group (92.9% vs 37.5% with ESD vs EMR), and the rate of perforation was also significantly higher (10.7% vs 0%). All cases of perforation were managed conservatively. No recurrence was observed in the ESD group, whereas local recurrences were detected in 12 EMR cases (21.4%). Eleven of the 12 recurrences (91.7%) were managed endoscopically, and one required surgical resection. Conclusions: Endoscopic submucosal dissection is a promising technique for the treatment of colorectal tumors, giving an excellent outcome in comparison with EMR.     

Warning for unprincipled colorectal endoscopic submucosal dissection: Accurate diagnosis and reasonable treatment strategy

Piecemeal endoscopic mucosal resection (EMR) is generally indicated for laterally spreading tumors (LST) >2 cm in diameter. However, the segmentation of adenomatous parts does not affect the histopathological diagnosis and completeness of cure. Thus, possible indications for piecemeal EMR are both adenomatous homogenous‐type granular‐type LST (LST‐G) and LST‐G as carcinoma in adenoma without segmentalizing the carcinomatous part. Diagnosis of the pit pattern using magnifying endoscopy is essential for determining the correct treatment and setting segmentation borders. In contrast, endoscopic submucosal dissection (ESD) is indicated for lesions requiring endoscopic en bloc excision, as it is difficult to use the snare technique for en bloc excisions such as in non‐granular‐type LST (LST‐NG), especially for the pseudodepressed type, tumors with a type V_I pit pattern, shallow invasive submucosal carcinoma, largedepressed tumors and large elevated lesions, which are often malignant (e.g. nodular mixed‐type LST‐G). Other lesions, such as intramucosal tumor accompanied by submucosal fibrosis, induced by biopsy or peristalsis of the lesion; sporadic localized tumors that occur due to chronic inflammation, including ulcerative colitis; and local residual early carcinoma after endoscopic treatment, are also indications for ESD. In clinical practice, an efficient endoscopic treatment with segregation of ESD from piecemeal EMR should be carried out after a comprehensive evaluation of the completeness of cure, safety, clinical simplicity, and cost–benefit, based on an accurate preoperative diagnosis.     

CURRENT TECHNIQUES AND DEVICES FOR SAFE AND CONVENIENT ENDOSCOPIC SUBMUCOSAL DISSECTION (ESD) AND KOREAN EXPERIENCE OF ESD

Conventional endoscopic mucosal resection (EMR) technique has limitations in its capacity of achieving en bloc resection and, for lesions greater than 20 mm, removal in a piecemeal resection is often required. This leads to uncertainty as to whether or not the lesion has been completely removed and to an increase in local recurrence. To overcome this limitation, a new technique using specifically designed cutting devices, termed endoscopic submucosal dissection (ESD) has been developed. The present article discuss the current indication, new diagnostic, cutting and hemostatic devices and long‐term outcomes of EMR and ESD in early gastric cancer in Korea.     

NOVEL TECHNIQUE OF ENDOSCOPIC SUBMUCOSAL DISSECTION USING AN EXTERNAL GRASPING FORCEPS FOR SUPERFICIAL GASTRIC NEOPLASIA

Endoscopic submucosal dissection (ESD) for early stage gastric cancer (EGC) has improved the success rate of en bloc resection but results in perforation more often than does endoscopic mucosal resection. We report a novel technique of ESD using an external grasping forceps. A total of 265 lesions with EGC or gastric adenoma were enrolled in this study. Sixteen lesions were located in the upper third portion of the stomach, 114 in the middle third portion, and 135 in the lower third portion. After submucosal injection followed by circumcision of the lesions with a flex knife, the external grasping forceps was introduced with the help of a second grasping forceps and anchored at the margin of the lesion. Oral traction applied with this forceps could elevate the lesion and make the submucosal layer wider and more visible, thereby facilitating dissection of the submucosal layer under direct vision. The mean lesion size was 15.0 mm (range: 5–50 mm). All but 11 lesions (95.8%) could be resected en bloc with free margins. Mean procedure time was 45 min (range: 20–180 min). It was difficult to carry out this procedure when the lesions were located in the cardia, lesser curvature, or posterior wall of the upper third of the gastric body. Bleeding after ESD occurred in 10 patients (3.8%) and perforation occurred in one patient (0.4%). The endoscopic submucosal dissection using an external grasping forceps for superficial gastric neoplasia is efficacious and safe.     

ENDOSCOPIC MUCOSAL RESECTION AND SUBMUCOSAL DISSECTION METHOD FOR LARGE COLORECTAL TUMORS

The goal of endoscopic mucosal resection (EMR) is to allow the endoscopist to obtain tissue or resect lesions not previously amenable to standard biopsy or excisional techniques and to remove malignant lesions without open surgery. In this article, we describe the results of conventional EMR and EMR using an insulation‐tipped (IT) electrosurgical knife (submucosal dissection method) for large colorectal mucosal neoplasms and discuss the problems and future prospects of these procedures. At present, conventional EMR is much more feasible than EMR using IT‐knife from the perspectives of time, money, complication, and organ preservation. However, larger lesions tend to be resected in a piecemeal fashion; and it is difficult to confirm whether EMR has been complete. For accurate histopathological assessment of the resected specimen en bloc EMR is desirable although further experience is needed to establish its safety and efficacy. Further improvements of in EMR with special knife techniques are required to simply and safely remove large colorectal neoplasms.     

重视并开展内镜黏膜下剥离术的规范化操作

内镜切除术治疗胃肠道早期肿瘤正日益被接受并开展应用,包括传统的内镜黏膜切除术（EMR）和近年开展的内镜黏膜下剥离术（ESD）。EMR对于15mm以上的病灶较难做到一次切除,而整块切除标本对病理学评估至关重要,ESD正是应这一要求开展起来的新技术。对局限于黏膜层的病变,ESD并不受其大小的限制,对部分早期胃肠道肿瘤,其可取代传统的手术治疗,但ESD需要相当高的内镜操作技术,术前需要多种方法对病灶进行谨慎、全面的评估,包括范围、浸润深度等,术中、术后还可能出现出血、穿孔等严重的并发症,其发生率远高于EMR。ESD的指征、操作技巧、病理评估等方面还需要不断完善。由于ESD在早期胃肠道肿瘤的治疗上具有很多优点,值得有条件医院的内镜医师予以重视并开展这一技术。     

Endoscopic submucosal dissection for gastric cancer

Opinion statement Endoscopic submucosal dissection (ESD) is a novel endoscopic treatment that enables a clinician to resect an early-stage gastric cancer in en bloc fashion. ESD is indicated for those cancers in which there is a high probability of en bloc resection and low probability of lymph node metastasis. The latter may be the limiting factor at institutions skilled at ESD. Several ESD techniques are available with similar outcomes. Thus, selection depends on operator preference and expertise. Gastrectomy with lymphadenectomy should be applied initially to those early gastric cancers with high probability of positive lymph nodes or as an additional treatment after ESD. Endoscopic mucosal resection (EMR) should be reserved for small, nonulcerated, intramucosal, differentiated cancers. Disadvantages of ESD in comparison with EMR are longer operation times and higher incidences of intraoperative bleeding and perforation, but the indication for ESD includes larger and ulcerative lesions not amenable to EMR.     

Endoscopic submucosal dissection of early gastric cancer

The purpose of this review was to examine a remarkable technical advance regarding the indications for and the technique of endoscopic resection of early gastric cancer. Endoscopic mucosal resection (EMR) of early gastric cancer with no risk of lymph node metastasis has been a standard technique in Japan, probably owing to the high incidence of gastric cancer in Japan and the fact that more than half of Japanese gastric cancer cases are diagnosed at an early stage. Very recently, several EMR techniques have become increasingly accepted and regularly used in Western countries. Although these minimally invasive techniques are safe, convenient, and efficacious, they are unsuitable for large lesions in particular. Difficulty in correctly assessing the depth of tumor invasion and an increase in local recurrence when standard EMR procedures are used have been reported in cases of large lesions, because such lesions are often resected piecemeal owing to the technical limitations of standard EMR. A new development in therapeutic endoscopy, called endoscopic submucosal dissection (ESD), allows the direct dissection of the submucosa, and large lesions can be resected en bloc. ESD is not limited by resection size and is expected to replace surgical resection. However, it is still associated with a higher incidence of complications than standard EMR procedures and requires a high level of endoscopic skill. The endoscopic indications, techniques, and management of complications of ESD for early gastric cancer for properly carrying out established therapeutic endoscopy are described.     

内镜黏膜下剥离术诊治高度可疑结直肠癌或癌前病变及共聚焦激光显微内镜在随访中的价值

目的探讨内镜黏膜下剥离术(Endoscopic submucosal dissection,ESD)治疗和诊断高度可疑或早期结直肠癌和癌前病变的有效性和安全性,比较整块活检病理与内镜活检病理对早期癌诊断意义及共聚焦激光显微内镜在随访中的价值。方法对于内镜下高度可疑早期结直肠癌或早期结直肠癌及癌前病变的19例患者行ESD治疗,术后评价ESD治疗相关的一次性整块切除率、组织学治愈性切除率、手术并发症;比较术后整块病理与术前内镜活检诊断符合率;在术后随访时用共聚焦激光显微内镜检查(1、3个月)以指导活检并观察局部复发情况。结果 19处病灶一次性整块切除率为94.7%(18/19),组织学治愈性切除率为84.2%(16/19);病变平均大小(2.3±0.5)cm,平均手术时间(70±19.4)min;术后腹痛2例,延迟性出血1例,内镜下钛夹止血成功,其余病例未发生急性或延迟性出血以及穿孔;术后病理:黏膜内癌7例,癌前病变10例,黏膜下癌2例,其中2例黏膜下癌均进一步补充开腹手术,术后切除病变肠段未发现癌组织残留和周边淋巴结转移;所有病例术后平均随访(24.6±8.0)个月,局部未见残留、复发及异时病灶发生;其中7例黏膜内癌ESD术后1、3个月采用共聚焦激光显微内镜检查以指导活检进行随访未见癌组织残留及复发。19处病灶ESD术后大块组织病理诊断符合率为100%,而术前活检病理诊断符合率仅为57.9%,有统计学意义(P0.01)。结论 ESD具有较高一次性整块切除率和组织学治愈性切除率,是一种治疗和诊断高度可疑或早期结直肠癌病变或癌前病变的安全有效的方法。共聚焦激光显微内镜可能对早期结直肠癌的术后随访具有一定的价值。     

Endoscopic Diagnosis and Treatment of Local Residual/Recurrent Lesions after Endoscopic Mucosal Resection for Early Colorectal Carcinoma

Local residual/recurrent lesions have been observed with some frequency after endoscopic mucosal resection (EMR) for colorectal tumors. Many reports have revealed that the rate of recurrence after piecemeal resection is higher than that after en bloc resection. Thus, to accomplish an appropriate trimming in EMR, it is important to closely observe the lesions to be resected, possibly by magnification. Our data show that, with careful trimming of lesions, there are no significant differences in rates of local residual recurrence between en bloc and piecemeal resections. The manner of recurrence and the biological characteristics of residual/recurrent tumors depend on whether the resected lesion is an adenoma, carcinoma in adenoma, de novo carcinoma, mucosal (m) or submucosal (sm) carcinoma. Therefore, it is essential to choose the appropriate method of follow‐up observation according to histopathologic findings of resected lesions. In local residual/recurrent lesions of intramucosal carcinomas, the treatment policy should be decided from an overall evaluation of histological findings on both recurrent and resected primary lesions. After EMR of sm carcinomas, attention should always be paid to both the loci of resection and possible metastasis during follow‐up observation; surgical treatment is inevitable in the case of recurrence.     

ENDOSCOPIC SUBMUCOSAL DISSECTION FOR COLORECTAL NEOPLASIA

Aim: Endoscopic submucosal dissection (ESD) has been positively applied to and gradually standardized for early gastric cancer; however, it is not widely used in the colorectum because of its technical difficulty. Methods: To increase the safety and ease of carrying out colon ESD, we developed a new scissors‐type device that we call the stag beetle knife (SBK). Here we report on our efforts to assess the efficacy and safety of colon ESD using the SBK. Results: ESD was carried out using SBK in 25 patients with colorectal neoplasia. All lesions were treated safety and easily, without any unexpected incisions. No delayed hemorrhage and perforation occurred. An en‐bloc resection and a negative resection margin were obtained in all cases. Conclusion: ESD using the SBK can be carried out with greater ease and safety for colorectal neoplasia.     

Clinical outcomes of endoscopic submucosal dissection and endoscopic mucosal resection for laterally spreading tumors larger than 20 mm

Background and Aims: Colorectal laterally spreading tumors (LST) > 20 mm are usually treated by endoscopic submucosal dissection (ESD) or endoscopic mucosal resection (EMR). Endoscopic piecemeal mucosal resection (EPMR) is sometimes required. The aim of our study was to compare the outcomes of ESD and EMR, including EPMR, for such LST. Methods: A total of 269 consecutive patients with a colorectal LST > 20 mm were treated endoscopically at our hospital from April 2006 to December 2009. We retrospectively evaluated the complications and local recurrence rates associated with ESD, hybrid ESD (ESD with EMR), EMR, and EPMR. Results: ESD and EMR were performed successfully for 89 and 178 LST, respectively: 61 by ESD; 28 by hybrid ESD; 70 by EMR; and 108 by EPMR. Between‐group differences in perforation rates were not significant. Local recurrence rates in cases with curative resection were as follows: 0% (0/56) in ESD; 0% (0/27) in hybrid ESD; 1.4% (1/69) in EMR; and 12.1% (13/107) in EPMR; that is, significantly higher in EPMR. No metastasis was seen at follow up. The recurrence rate for EPMR yielding ≥ three pieces was significantly high (P < 0.001). All 14 local recurrent lesions were adenomas that were cured endoscopically. Conclusions: As for safety, ESD/hybrid ESD is equivalent to EMR/EPMR. ESD/hybrid ESD is a feasible technique for en bloc resection and showed no local recurrence. Although local recurrences associated with EMR/EPMR were seen, which were conducted based on our indication criteria, all local recurrences could obtain complete cure by additional endoscopic treatment.     

Indications for and Technical Aspects of Colorectal Endoscopic Submucosal Dissection

Due to the widespread acceptance of gastric and esophageal endoscopic submucosal dissections (ESDs), the number of medical facilities that perform colorectal ESDs has grown and the effectiveness of colorectal ESD has been increasingly reported in recent years. The clinical indications for colorectal ESD at the National Cancer Center Hospital, Tokyo, Japan include laterally spreading tumor (LST) nongranular type lesions >20 mm and LST granular type lesions >30 mm. In addition, 0-IIc lesions >20 mm, intramucosal tumors with nonlifting signs and large sessile lesions, all of which are difficult to resect en bloc by conventional endoscopic mucosal resection (EMR), represent potential candidates for colorectal ESD. Rectal carcinoid tumors less than 1 cm in diameter can be treated simply, safely, and effectively by endoscopic submucosal resection using a ligation device and are therefore not indications for ESD. The en bloc resection rate was 90%, and the curative resection rate was 87% for 806 ESDs. The median procedure time was 60 minutes, and the mean size for resected specimens was 40 mm (range, 15 to 150 mm). Perforations occurred in 23 (2.8%) cases, and postoperative bleeding occurred in 15 (1.9%) cases, but only two perforation cases required emergency surgery (0.25%). ESD was an effective procedure for treating colorectal tumors that are difficult to resect en bloc by conventional EMR. ESD resulted in a higher en bloc resection rate as well as decreased invasiveness in comparison to surgery. Based on the excellent clinical results of colorectal ESDs in Japan, the Japanese healthcare insurance system has approved colorectal ESD for coverage.     

Local recurrence of large squamous-cell carcinoma of the esophagus after endoscopic resection

BACKGROUND: A new technique, endoscopic submucosal dissection (ESD), which uses specially developed endoscopic knives, was recently developed for en bloc resection of large lesions. Despite increasing indications for endoscopic resection (ER), there are limited data available regarding the outcome of ER for lesions 20 mm or more in diameter. OBJECTIVE: To investigate the risk factors for local recurrence. DESIGN: Retrospective cohort study. SETTING: A cancer-referral center. PATIENTS: Seventy patients, who presented between September 1994 and April 2006, with a total of 78 lesions that measured 20 mm or more in diameter. MAIN OUTCOME MEASUREMENT: Local recurrence rate after ER was assessed. RESULTS: At a median follow-up of 32 months (range 12-121 months), there were 12 local recurrences (15.4%). There was no significant association between local recurrence and multiple iodine-voiding lesions, tumor size, or tumor location. The number of resections and the resection method, however, were significantly associated with local recurrence. There was no recurrence of lesions treated by en bloc resection. Lesions resected in 5 or more pieces had a significantly higher recurrence rate than lesions resected in 2 to 4 pieces. Lesions treated by EMR had a significantly higher recurrence rate than lesions treated by ESD. LIMITATIONS: Single-center retrospective analysis. CONCLUSIONS: Esophageal squamous-cell carcinoma that measured 20 mm or more in diameter should be resected en bloc by ESD. Lesions treated by resection in 5 or more pieces have a higher risk for local recurrence.     

ENDOSCOPIC SUBMUCOSAL DISSECTION FOR THE RELIABLE EN BLOC RESECTION OF COLORECTAL MUCOSAL TUMORS

Scheduled piecemeal resection has been actively conducted for granular type laterally spreading tumor (LST‐G) in Japan, as long as a definite preoperative diagnosis is made. However, en bloc resection is desirable for depressed lesions (e.g. IIc lesion) as well as non‐granular type laterally spreading tumor (LST‐NG) since they have considerable high risk for submucoasl invasion and require precise histopathological evaluation. Endoscopic submucosal dissection (ESD) has been developed for the en bloc resection of mucosal tumors of gastrointestinal tract and widely applied especially in gastric lesions. Although the large intestine involves structural and technical difficulties, we conducted en bloc resection by ESD while exercising sorts of ingenuity for preparation; endoscopes, instruments, local injections, and others. ESD is a reliable technique that allows en bloc resection of gastrointestinal mucosal lesions, and even has a splendid possibility for the treatment of early stage colorectal cancer.     

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。