Endoscopic diagnosis and treatment of superficial nonampullary duodenal tumors

The diagnostic and treatment guidelines of superficial non-ampullary duodenal tumors have not been standardized due to their low prevalence.Previous reports suggested that a superficial adenocarcinoma(SAC) should be treated via local resection because of its low risk of lymph node metastasis,whereas a highgrade adenoma(HGA) should be resected because of its high risk of progression to adenocarcinoma.Therefore,pretreatment diagnosis of SAC or HGA is important to determine the appropriate treatment strategy.There are certain endoscopic features known to be associated with SAC or HGA,and current practice prioritizes the endoscopic and biopsy diagnosis of these conditions.Surgical treatment of these duodenal lesions is often related to high risk of morbidity,and therefore endoscopic resection has become increasingly common in recent years.Endoscopic mucosal resection(EMR) and endoscopic submucosal dissection(ESD) are the commonly performed endoscopic resection methods.EMR is preferred due to its lower risk of adverse events;however,it has a higher risk of recurrence than ESD.Recently,a new and safer endoscopic procedure that reduces adverse events from EMR or ESD has been reported.     

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.     

Importance of histological evaluation in endoscopic resection of early colorectal cancer

The diagnostic criteria for colonic intraepithelial tumors vary from country to country.While intramucosal adenocarcinoma is recognized in Japan,in Western countries adenocarcinoma is diagnosed only if the tumor invades to the submucosa and accesses the muscularis mucosae.However,endoscopic therapy,including endoscopic mucosal resection(EMR)and endoscopic submucosal dissection(ESD),is used worldwide to treat adenoma and early colorectal cancer.Precise histopathological evaluation is important for the curativeness of these therapies as inappropriate endoscopic therapy causes local recurrence of the tumor that may develop into fatal metastasis.Therefore,colorectal ESD and EMR are not indicated for cancers with massive submucosal invasion.However,diagnosis of cancer with massive submucosal invasion by endoscopy is limited,even when magnifying endoscopy for pit pattern and narrow band imaging and flexible spectral imaging color of enhancement are performed.Therefore,occasional cancers with massive submucosal invasion will be treated by ESD and EMR.Precise histopathological evaluation of these lesions should be performed in order to determine the necessity of additional therapy,including surgical resection.     

RISK MANAGEMENT OF THERAPEUTIC COLONOSCOPY (HOT BIOPSY,POLYPECTOMY, ENDOSCOPIC MUCOSAL RESECTION AND ENDOSCOPIC SUBMUCOSAL DISSECTION)

The concept of an adenoma–carcinoma sequence has been widely accepted in the colon and rectum, contrary to that in gastric cancer. Consequently, most target lesions for endoscopic resection using these newly developed techniques are histologically assessed as adenoma or intramucosal carcinoma in adenoma. Based on results in conventional endoscopic mucosal resection (EMR), almost all remnant or recurrent tumors can be successfully managed by salvage EMR, and all materials resected by salvage EMR also showed adenoma or intramucosal cancer. These results suggest that en bloc resection is not always clinically necessary to obtain complete cure for all colorectal neoplasia. However, larger lesions tend to be resected in a piecemeal fashion; it is difficult to confirm whether EMR has been completed or not. For precise histopathological assessment of the resected specimen, endoscopic submucosal dissection (ESD) for en bloc resection is desirable, although further experience is needed to establish its safety and efficacy. The present review contains a summary of the risk management of therapeutic colonoscopy including ESD for large colorectal mucosal neoplasia, debated at the Endoscopic Forum Japan 2006, Hakone, and discussion of the problems and future prospects of these procedures.     

Unveiling lymph node metastasis in early gastric cancer

With respect to gastric cancer treatment,improvements in endoscopic techniques and novel therapeutic modalities[such as endoscopic mucosal resection(EMR)and endoscopic submucosal dissection(ESD)]have been developed.Currently,EMR/ESD procedures are widely accepted treatment modalities for early gastric cancer(EGC).These procedures are most widely accepted in Asia,including in Korea and Japan.In the present era of endoscopic resection,accurate prediction of lymph node(LN)metastasis is a critical component of selecting suitable patients for EMR/ESD.Generally,indications for EMR/ESD are based on large Japanese datasets,which indicate that there is almost no risk of LN metastasis in the subgroup of EGC cases.However,there is some controversy among investigators regarding the validity of these criteria.Further,there are currently no accurate methods to predict LN metastasis in gastric cancer(for example,radiologic methods or methods based on molecular biomarkers).We recommend the use of a 2-step method for the management of early gastric cancer using endoscopic resection.The first step is the selection of suitable patients for endoscopic resection,based on endoscopic and histopathologic findings.After endoscopic resection,additional surgical intervention could be determined on the basis of a comprehensive review of the endoscopic mucosal resection/endoscopic submucosal dissection specimen,including lymphovascular tumor emboli,tumor size,histologic type,and depth of invasion.However,evaluation of clinical application data is essential for validating this recommendation.Moreover,gastroenterologists,surgeons,and pathologists should closely collaborate and communicate during these decisionmaking processes.     

Endoscopic mucosal resection and endoscopic submucosal dissection in the treatment of sporadic nonampullary duodenal adenomatous polyps

Although uncommon, sporadic nonampullary duodenal adenomas have a growing detection due to the widespread of endoscopy. Endoscopic therapy is being increasingly used for these lesions, since surgery, considered the standard treatment, carries significant morbidity and mortality. However, the knowledge about its risks and benefits is limited, which contributes to the current absence of standardized recommendations. This review aims to discuss the efficacy and safety of endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) in the treatment of these lesions. A literature review was performed, using the Pubmed database with the query: “(duodenum or duodenal) (endoscopy or endoscopic) adenoma resection”, in the human species and in English. Of the 189 retrieved articles, and after reading their abstracts, 19 were selected due to their scientific interest. The analysis of their references, led to the inclusion of 23 more articles for their relevance in this subject. The increased use of EMR in the duodenum has shown good results with complete resection rates exceeding 80% and low complication risk (delayed bleeding in less than 12% of the procedures). Although rarely used in the duodenum, ESD achieves close to 100% complete resection rates, but is associated with perforation and bleeding risk in up to one third of the cases. Even though literature is insufficient to draw definitive conclusions, studies suggest that EMR and ESD are valid options for the treatment of nonampullary adenomas. Thus, strategies to improve these techniques, and consequently increase the effectiveness and safety of the resection of these lesions, should be developed.     

Endoscopic submucosal dissection for superficial esophageal squamous cell neoplasms

Endoscopic resection is an effective treatment for noninvasive esophageal squamous cell neoplasms(ESCNs).Endoscopic mucosal resection(EMR)has been developed for small localized ESCNs as an alternative to surgical therapy because it shows similar effectiveness and is less invasive than esophagectomy.However,EMR is limited in resection size and therefore piecemeal resection is performed for large lesions,resulting in an imprecise histological evaluation and a high frequency of local recurrence.Endoscopic submucosal dissection(ESD)has been developed in Japan as one of the standard endoscopic resection techniques for ESCNs.ESD enables esophageal lesions,regardless of their size,to be removed en bloc and thus has a lower local recurrence rate than EMR.The development of new devices and the establishment of optimal strategies for esophageal ESD have resulted in fewer complications such as perforation than expected.However,esophageal stricture after ESD may occur when the resected area is larger than three-quarters of the esophageal lumen or particularly when it encompasses the entire circumference;such a stricture requires multiple sessions of endoscopic balloon dilatation.Recently,oral prednisolone has been reported to be useful in preventing post-ESD stricture.In addition,a combination of chemoradiotherapy(CRT)and ESD might be an alternative therapy for submucosal esophageal cancer that has a risk of lymph node metastasis because esophagectomy is extremely invasive;CRT has a higher local recurrence rate than esophagectomy but is less invasive.ESD is likely to play a central role in the treatment of superficial esophageal squamous cell neoplasms in the future.     

内镜下黏膜剥离术在高风险/高难度病例治疗中的应用

内镜下黏膜剥离术(ESD)已越来越多地应用于消化道早期肿瘤及癌前病变的微创治疗。与内镜下黏膜切除术(EMR)相比,ESD可完整切除病灶,切除较大病灶、平坦型病灶以及溃疡型病灶,从而利于完整的病理学诊断及减少复发,且相对外科手术来说,其安全性高、死亡率低、损伤小、恢复快,具有与外科手术类似的治疗效果,为消化道早期肿瘤的治疗开辟了新的途径。本文就ESD在切除特殊病灶(巨大肿瘤、十二指肠肿瘤、胃黏膜下肿瘤和咽喉癌)及在特殊患者(早期残胃癌、高龄、肝硬化和慢性肾功能衰竭血透患者)中的应用作一概述。     

Endoscopic submucosal dissection and surgical treatment for gastrointestinal cancer

Endoscopic submucosal dissection (ESD) is widely usedin Japan as a minimally invasive treatment for earlygastric cancer. The application of ESD has expanded tothe esophagus and colorectum. The indication criteriafor endoscopic resection (ER) are established for eachorgan in Japan. Additional treatment, including surgery with lymph node dissection, is recommended when pathological examinations of resected specimens donot meet the criteria. Repeat ER for locally recurrent gastrointestinal tumors may be difficult because of submucosal fibrosis, and surgical resection is required inthese cases. However, ESD enables complete resectionin 82%-100% of locally recurrent tumors. Transanal endoscopic microsurgery (TEM) is a well-developed sur-gical procedure for the local excision of rectal tumors.ESD may be superior to TEM alone for superficial rectaltumors. Perforation is a major complication of ESD,and it is traditionally treated using salvage laparotomy.However, immediate endoscopic closure followed byadequate intensive treatment may avoid the need forsurgical treatment for perforations that occur during ESD. A second primary tumor in the remnant stomach after gastrectomy or a tumor in the reconstructedorgan after esophageal resection has traditionally required surgical treatment because of the technical difficulty of ER. However, ESD enables complete resectionin 74%-92% of these lesions. Trials of a combination ofESD and laparoscopic surgery for the resection of gastric submucosal tumors or the performance of sentinellymph node biopsy after ESD have been reported, butthe latter procedure requires a careful evaluation of itsclinical feasibility.     

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.     

超声内镜联合EMR或ESD在食管表浅隆起性病变诊断和治疗中的作用

目的：探讨超声内镜（EUS）联合内镜下黏膜切除术（EMR）或内镜下黏膜剥离术（ESD）在食管表浅隆起性病变诊断和治疗中的价值。方法对35例经EUS检查拟诊为食管表浅隆起性病变患者进行EMR或ESD治疗的病例资料进行回顾性研究,分析病变部位的EUS图像、病理诊断结果及随访治疗效果。结果35例中21例经EMR治疗,14例经ESD治疗。经病理组织学检查确诊为早期食管癌9例,重度不典型增生5例,良性间质瘤3例,腺瘤性息肉4例,非腺瘤性息肉6例,平滑肌瘤8例。经EUS及病理证实病变均起源于黏膜层、黏膜肌层和黏膜下层。34例分别于术后1、3、6月复查EUS随访,术后1个月后伤口均完全愈合,无出血、食管狭窄及局部复发现象发生。结论联合应用EUS和EMR或ESD技术,不仅可以提高食管表浅隆起性病变早期的确诊率,而且是一种微创、有效、安全、快速的治疗措施。     

内镜治疗早期肠道肿瘤相关问题探讨

内镜黏膜下剥离术(ESD)与内镜黏膜切除术(EMR)是消化道内镜手术中的两种重要手术方式,目前基于两者又出现了改良的新术式：ESD-S(ESD with snare,ESD联合圈套器法)与EMR-P术(EMR with precutting,预环切EMR法)。这四种手术方式在治疗结直肠肿瘤中具有各自不同的优缺点,如较高的完全切除率,较低的并发症风险等。综合近几年国际发表的临床试验,笔者认为：对于直径小于20 mm的结直肠肿瘤,可根据肿瘤的情况,选择ESD术、ESD-S术,EMR-P术或者EMR术。对于直径大于20 mm的肿瘤,ESD术与ESD-S术由于其较低的复发率与较高的完全切除率,可以作为处理此类肿瘤的首选。如上述两种术式风险较高,可以采用EMR-P进行处理。EMR术由于完全切除率较低,复发率偏高,而大于20 mm肿瘤恶变风险较高,不适合用于这类肿瘤的切除。     

Indications and outcomes of endoscopic resection for non-pedunculated colorectal lesions: A narrative review

In the last years, endoscopic techniques gained a crucial role in the treatment of colorectal flat lesions. At the same time, the importance of a reliable assessment of such lesions to predict the malignancy and the depth of invasion of the colonic wall emerged. The current unsolved dilemma about the endoscopic excision techniques concerns the necessity of a reliable submucosal invasive cancer assessment system that can stratify the risk of the post-procedural need for surgery. Accordingly, this narrative literature review aims to compare the available diagnostic strategies in predicting malignancy and to give a guide about the best techniques to employ. We performed a literature search using electronic databases (MEDLINE/PubMed, EMBASE, and Cochrane Library). We collected all articles about endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) registering the outcomes. Moreover, we analyzed all meta-analyses comparing EMR vs ESD outcomes for colorectal sessile or non-polypoid lesions of any size, preoperatively estimated as non-invasive. Seven meta-analysis studies, mainly Eastern, were included in the analysis comparing 124 studies and overall 22954 patients who underwent EMR and ESD procedures. Of these, eighty-two were retrospective, twenty-four perspective, nine case-control, and six cohorts, while three were randomized clinical trials. A total of 18118 EMR and 10379 ESD were completed for a whole of 28497 colorectal sessile or non-polypoid lesions > 5-10 mm in size. In conclusion, it is crucial to enhance the preoperative diagnostic workup, especially in deciding the most suitable endoscopic method for radical resection of flat colorectal lesions at risk of underlying malignancy. Additionally, the ESD necessitates further improvement because of the excessively time-consuming as well as the intraprocedural technical hindrances and related complications. We found a higher rate of en bloc resections and R0 for ESD than EMR for non-pedunculated colorectal lesions. Nevertheless, despite the lower local recurrence rates, ESD had greater perforation rates and needed lengthier procedural times. The prevailing risk for additional surgery in ESD rather than EMR for complications or oncologic reasons is still uncertain.     

Treatment modalities for early gastric cancer

Different treatment modalities have been proposed in the treatment of early gastric cancer (EGC). Endoscopic resection (ER) is an established treatment that allows curative treatment, in selected cases. In addition, ER allows for an accurate histological staging, which is crucial when deciding on the best treatment option for EGC. Recently, endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) have become alternatives to surgery in early gastric cancer, mainly in Asian countries. Patients with “standard” criteria can be successfully treated by EMR techniques. Those who meet “expanded” criteria may benefit from treatment by ESD, reducing the need for surgery. Standardized ESD training system is imperative to promulgate effective and safe ESD technique to practices with limited expertise. Although endoscopic resection is an option in patients with EGC, surgical treatment continues to be a widespread therapeutic option worldwide. In this review we tried to point out the treatment modalities for early gastric cancer.     

Long-term follow up of endoscopic resection for type 3 gastric NET

AIM:To clarify the short and long-term results and to prove the usefulness of endoscopic resection in type 3gastric neuroendocrine tumors(NETs).METHODS:Of the 119 type 3 gastric NETs diagnosed from January 1996 to September 2011,50 patients treated with endoscopic resection were enrolled in this study.For endoscopic resection,endoscopic mucosal resection(EMR)or endoscopic submucosal dissection(ESD)was used.Therapeutic efficacy,complications,and follow-up results were evaluated retrospectively.RESULTS:EMR was performed in 41 cases and ESD in 9 cases.Pathologically complete resection was performed in 40 cases(80.0%)and incomplete resection specimens were observed in 10 cases(7 vs 3 patients in the EMR vs ESD group,P=0.249).Upon analysis of the incomplete resection group,lateral or vertical margin invasion was found in six cases(14.6%)in the EMR group and in one case in the ESD group(11.1%).Lymphovascular invasions were observed in two cases(22.2%)in the ESD group and in one case(2.4%)in the EMR group(P=0.080).During the follow-up period(43.73;13-60 mo),there was no evidence of tumor recurrence in either the pathologically complete resection group or the incomplete resection group.No recurrence was reported during follow-up.In addition,no mortality was reported in either the complete resection group or the incomplete resection group for the duration of the follow-up period.CONCLUSION:Less than 2 cm sized confined submucosal layer type 3 gastric NET with no evidence of lymphovascular invasion,endoscopic treatment could be considered at initial treatment.     

Future directions of duodenal endoscopic submucosal dissection

Endoscopic therapies for lesions of the duodenum are technically more difficult than those for lesions of the other parts of the gastrointestinal tract due to the anatomical features of the duodenum, and the incidence rate of complications such as perforation and bleeding is also higher. These aforementioned trends were especially noticeable for the case of duodenal endoscopic submucosal dissection(ESD). The indication for ESD of duodenal tumors should be determined by assessment of the histopathology, macroscopic morphology, and diameter of the tumors. The three types of candidate lesions for endoscopic therapy are adenoma, carcinoma, and neuroendocrine tumors. For applying endoscopic therapies to duodenal lesions, accurate preoperative histopathological diagnosis is necessary. The most important technical issue in duodenal ESD is the submucosal dissection process. In duodenal ESD, a short needle-type knife is suitable for the mucosal incision and submucosal dissection processes, and the Small-caliber-tip Transparent hood is an important tool. After endoscopic therapies, the wound should be closed by clipping in order to prevent complications such as secondary hemorrhage and delayed perforation. At present, the criteria for selection between ESD and EMR vary among institutions. The indications for ESD should be carefully considered. Duodenal ESD should have limitations, such as the need for its being performed by experts with abundant experience in performing the procedure.     

Chicken soup for teaching and learning ESD

Endoscopic submucosal dissection(ESD) is becoming a popular procedure for the diagnosis and treatment of superficial mucosal lesions,and has the advantage of en bloc resection which yields a higher complete resection and remission rate compared to endoscopic mucosal resection(EMR).However,the learning process of this advanced endoscopic procedure requires a lengthy training period and considerable experience to be proficient.A well framed training protocol which is safe,effective,easily reproducible and cos...     

Early gastric cancer: diagnosis, pathology, treatment techniques and treatment outcomes

Recent improvements in endoscopic techniques and technologies and an increased understanding and recognition of the importance of early gastric cancer (EGC) will result in increases in the detection and diagnosis of precancerous or early cancerous lesions. The incidences of nodal metastasis of intramucosal and submucosal EGC are 3 and 20%, respectively. Therefore, major surgery may be inappropriate in many of these patients, and many cases of EGC may be treated by endoscopic mucosal resection (EMR). EMR was first introduced in Japan 20 years ago. Most EMR have been performed by the so-called 'strip biopsy' or EMR-C methods. However, we have sometimes experienced local recurrence in cases that had been resected in multiple fragments by these methods. To obtain 'complete resection', we developed the endoscopic submucosal dissection (ESD) technique using a special endoscopic knife, the insulation-tipped diathermic knife (IT knife). The rate of complete resection, i.e. cut margin free from cancer and one-piece resection, was remarkably higher for the IT knife technique than conventional EMR. ESD cases are increasing rapidly in Japan. EMR including ESD is a good method for patients with gastric cancer to preserve the stomach. For EMR, it is necessary to find EGC. Both diagnosis and treatment are important, and scientific data regarding lymph node metastasis and clinicopathological features are required.     

Management of a large mucosal defect after duodenal endoscopic resection

Duodenal endoscopic resection is the most difficult type of endoscopic treatment in the gastrointestinal tract (GI) and is technically challenging because of anatomical specificities. In addition to these technical difficulties, this procedure is associated with a significantly higher rate of complication than endoscopic treatment in other parts of the GI tract. Postoperative delayed perforation and bleeding are hazardous complications, and emergency surgical intervention is sometimes required. Therefore, it is urgently necessary to establish a management protocol for preventing serious complications. For instance, the prophylactic closure of large mucosal defects after endoscopic resection may reduce the risk of hazardous complications. However, the size of mucosal defects after endoscopic submucosal dissection (ESD) is relatively large compared with the size after endoscopic mucosal resection, making it impossible to achieve complete closure using only conventional clips. The over-the-scope clip and polyglycolic acid sheets with fibrin gel make it possible to close large mucosal defects after duodenal ESD. In addition to the combination of laparoscopic surgery and endoscopic resection, endoscopic full-thickness resection holds therapeutic potential for difficult duodenal lesions and may overcome the disadvantages of endoscopic resection in the near future. This review aims to summarize the complications and closure techniques of large mucosal defects and to highlight some directions for management after duodenal endoscopic treatment.