Treatment for superficial non-ampullary duodenal epithelial tumors

Because of the low prevalence of non-ampullary duodenal epithelial tumors (NADETs), standardized clinical management of sporadic superficial NADETs, including diagnosis, treatment, and follow-up, has not yet been established. Retrospective studies have revealed certain endoscopic findings suggestive of malignancy. Duodenal adenoma with high-grade dysplasia and mucosal cancer are candidates for local resection by endoscopic or minimally invasive surgery. The use of endoscopic treatment including endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD), for the treatment for superficial NADETs is increasing. EMR requires multiple sessions to achieve complete remission and repetitive endoscopy is needed after resection. ESD provides an excellent complete resection rate, however it remains a challenging method, considering the high risk of intraoperative or delayed perforation. Minimally invasive surgery such as wedge resection and pancreas-sparing duodenectomy are beneficial for superficial NADETs that are technically difficult to remove by endoscopic treatment. Pancreaticoduodenectomy remains a standard surgical procedure for treatment of duodenal cancer with submucosal invasion, which presents a risk of lymph node metastasis. Endoscopic or surgical treatment outcomes of superficial NADETs without submucosal invasion are satisfactory. Establishing an endoscopic diagnostic tool to differentiate superficial NADETs between adenoma and cancer as well as between mucosal and submucosal cancer is required to select the most appropriate treatment.     

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.     

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.     

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.     

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.     

Superficial tumors involving terminal ileum treated by endoscopic submucosal dissection

It is recognized that superficial tumors of the ileocecal transition pose a higher degree of complexity for endoscopic resection and surgical treatment is sometimes required in cases of incomplete resection. We report some rare cases of superficial tumors involving the terminal ileum treated by endoscopic submucosal dissection (ESD). A 58-year-old woman was referred to our hospital for treatment of a superficial tumor involving the terminal ileum. Endoscopy showed a slightly elevated (type 0-IIa) tumor located at the ileocecal transition. The tumor could be resected en bloc by ESD with a combination of a small-caliber-tip transparent hood and a flex knife without any complications. A 61-year-old man was also referred to our hospital for treatment of a slightly elevated (type 0-IIa) tumor located at the ileocecal transition. The tumor could be resected en bloc. Both resected specimens showed intramucosal adenocarcinomas with clear lateral and vertical margins. By applying ESD with a combination of a flex knife and a small-caliber-tip transparent hood, the superficial tumors involving the terminal ileum were resected en bloc without any complications and the ileocecal valve was preserved in both cases.     

Endoscopic submucosal tunnel dissection for large superficial esophageal squamous cell neoplasms

Endoscopic submucosal dissection (ESD) is a well-established treatment for superficial esophageal squamous cell neoplasms (SESCNs) with no risk of lymphatic metastasis. However, for large SESCNs, especially when exceeding two-thirds of the esophageal circumference, conventional ESD is time-consuming and has an increased risk of adverse events. Based on the submucosal tunnel conception, endoscopic submucosal tunnel dissection (ESTD) was first introduced by us to remove large SESCNs, with excellent results. Studies from different centers also reported favorable results. Compared with conventional ESD, ESTD has a more rapid dissection speed and R0 resection rate. Currently in China, ESTD for large SESCNs is an important part of the digestive endoscopic tunnel technique, as is peroral endoscopic myotomy for achalasia and submucosal tunnel endoscopic resection for submucosal tumors of the muscularis propria. However, not all patients with SESCNs are candidates for ESTD, and postoperative esophageal strictures should also be taken into consideration, especially for lesions with a circumference greater than three-quarters. In this article, we describe our experience, review the literature of ESTD, and provide detailed information on indications, standard procedures, outcomes, and complications of ESTD.     

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。     

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.     

Safety and curative ability of endoscopic submucosal dissection for superficial esophageal cancers at least 50 mm in diameter

Background and Aim: Limited data are available regarding the use of endoscopic submucosal dissection (ESD) for superficial esophageal cancers ≥50 mm in diameter. The aim of the present study was to investigate the safety and success of ESD for superficial esophageal cancers ≥50 mm. Methods: A total of 39 patients with superficial esophageal squamous cell carcinoma ≥50 mm were treated with ESD at Osaka Medical Center for Cancer and Cardiovascular Diseases between January 2004 and April 2011, and were analyzed in a retrospective study. Results: En bloc resection was achieved in all patients. One mediastinal emphysema without perforation occurred during the procedure. Stricture developed in 11 of 39 patients, requiring a median of five endoscopic balloon dilatation procedures. Thirty‐three clinical epithelial or lamina propria mucosal cancers were treated by ESD with curative intent, of which invasion into the muscularis mucosa or deeper was detected in seven and lymphovascular involvement in three. The en bloc resection rate was 100% with a tumor‐free margin achieved in 92% of lesions. The curative resection and complication rates during ESD were 70% and 2.5%, respectively. Conclusion: ESD achieved a high en bloc resection rate of 92% with a tumor‐free margin. Curative resection rate of ESD in patients with clinical epithelial or lamina propria mucosal cancers was not low at 70%. However, the risk of stricture must be taken into account when considering the use of ESD in lesions ≥50 mm.     

Curative ESD for intraepithelial esophageal carcinoma with leiomyoma mimicking submucosal invasive carcinoma

This case report presents a 65-year-old man who developed early esophageal cancer with leiomyoma treated by endoscopic submucosal dissection (ESD). There have been several reports of co-existing superficial esophageal cancer and leiomyoma treated by endoscopic mucosal resection. However, there is no previous report describing the co-existing lesion treated by ESD. In order to determine treatment strategies for esophageal cancer, accurate endoscopic evaluation of the cancerous depth is essential. In the present case, the combination of endoscopic ultrasonography and narrow-band imaging system with magnifying endoscopy was extremely useful to evaluate the superficial esophageal cancer with leiomyoma, which lead to the appropriate treatment, ESD.     

Endoscopic submucosal dissection-current success and future directions

More than 10 years have passed since endoscopic submucosal dissection (ESD) was first developed in Japan. ESD enables en bloc complete resection of superficial gastrointestinal neoplasms regardless of the size and location of the lesions. With improvements in techniques and devices, excellent therapeutic results have been achieved despite the inherent technical difficulties of this procedure. ESD aiming for curative treatment can be performed for gastrointestinal neoplasms without risk of lymph node metastasis. Accurate histopathologic examination of the resected specimen is required to determine the risk of lymph node metastasis, for which en bloc resection is beneficial. Owing to the high success rate of en bloc complete resection and accurate histopathologic examination, tumour recurrence rates after ESD are reported to be very low in Japan. Excellent results of ESD in a large number of cases have also been reported from other Asian countries such as South Korea, Taiwan and China. Although scepticism exists among Western clinicians regarding the application of ESD, it is developing slowly and reports indicate promising results in some European countries. With further development of technologies, such as endoscopic robotics, ESD could become the worldwide treatment of choice for early gastrointestinal neoplasms.     

Predictive factors for esophageal stenosis after endoscopic submucosal dissection for superficial esophageal cancer

Endoscopic submucosal dissection (ESD) has been utilized as an alternative treatment to endoscopic mucosal resection for superficial esophageal cancer. We aimed to evaluate the complications associated with esophageal ESD and elucidate predictive factors for post‐ESD stenosis. The study enrolled a total of 42 lesions of superficial esophageal cancer in 33 consecutive patients who underwent ESD in our department. We retrospectively reviewed ESD‐associated complications and comparatively analyzed regional and technical factors between cases with and without post‐ESD stenosis. The regional factors included location, endoscopic appearance, longitudinal and circumferential tumor sizes, depth of invasion, and lymphatic and vessel invasion. The technical factors included longitudinal and circumferential sizes of mucosal defects, muscle disclosure and cleavage, perforation, and en bloc resection. Esophageal stenosis was defined when a standard endoscope (9.8 mm in diameter) failed to pass through the stenosis. The results showed no cases of delayed bleeding, three cases of insidious perforation (7.1%), two cases of endoscopically confirmed perforation followed by mediastinitis (4.8%), and seven cases of esophageal stenosis (16.7%). Monovalent analysis indicated that the longitudinal and circumferential sizes of the tumor and mucosal defect were significant predictive factors for post‐ESD stenosis (P < 0.005). Receiver operating characteristic analysis showed the highest sensitivity and specificity for a circumferential mucosal defect size of more than 71% (100 and 97.1%, respectively), followed by a circumferential tumor size of more than 59% (85.7 and 97.1%, respectively). It is of note that the success rate of en bloc resection was 95.2%, and balloon dilatation was effective for clinical symptoms in all seven patients with post‐ESD stenosis. In conclusion, the most frequent complication with ESD was esophageal stenosis, for which the sizes of the tumor and mucosal defect were significant predictive factors. Although ESD enables large en bloc resection of esophageal cancer, practically, in cases with a lesion more than half of the circumference, great care must be taken because of the high risk of post‐ESD stenosis.     

Effect of Endoscopic Submucosal Dissection for Superficial Esophageal Neoplasms and Risk Factors for Postoperative Stricture

Endoscopic submucosal dissection (ESD) enables wider tumor resection compared with endoscopic mucosal resection and en bloc resection of superficial esophageal neoplasms. However, ESD may cause difficult-to-treat stricture of the esophagus, and therefore, prediction of and measures against postoperative esophageal stricture are critical. The aim of this study was to evaluate the effect of ESD on superficial esophageal neoplasms and identify risk factors associated with esophageal stricture after ESD.This study included 165 lesions in 120 patients with superficial esophageal neoplasms, including cancer and neoplasia, who underwent ESD from 2009 to 2013.The complete resection rate of superficial esophageal neoplasms by ESD was 90.9%. After ESD, 22 subjects (18.3%) had symptomatic esophageal stricture, 12 (10.0%) had aspiration pneumonia of grade 2, and 7 (5.8%) had mediastinal emphysema of grade 2. Comparison of the 22 subjects with stricture with the 98 subjects without stricture showed significant differences in the rate of resection of >75% of the esophageal circumference, rate of whole circumference resection, and the required time for resection. The tumor size and the size of the resected tissue sample also differed between the 2 groups. The groups did not differ in age, sex, alcohol intake, and smoking; location, macroscopic, and histological tumor findings; chest pain; or use of anticoagulants for comorbidities. In multivariate analysis, tumor size and whole circumference resection were independent risk factors for stricture. Furthermore, in 45 subjects with resection of >75% of the esophageal circumference, whole resection of the esophagus was the only independent risk factor for stricture.This study suggests that ESD has a strong therapeutic effect on superficial esophageal neoplasms; however, a greater extent of resection of the esophagus increases the risk of postoperative esophageal stricture. Preventive measures against development of postoperative stricture require further study.     

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.     

Endoscopic submucosal dissection using flexknife

Although the standard treatment for early-stage gastrointestinal tumors is still surgical resection, endoscopic resection has been accepted for some of these lesions, especially in Japan. However, the indication was limited until recently to achieve en bloc resection and prevent local recurrence. To overcome the disadvantage of endoscopic resection with conventional endoscopic mucosal resection (EMR), several investigators, including us, have developed a new endoscopic resection technique: endoscopic submucosal dissection (ESD). ESD is a remarkable technique that enables to remove the lesions en bloc regardless of size, shape, coexisting ulcer, and location. Nowadays, several knives are available for ESD, such as the needle knife, insulation-tipped (IT) knife, Hookknife, triangle-tipped (TT) knife, and Flexknife. Each of them has some merits and demerits, and the ways to use the knives are different. We summarize here how to use the Flexknife, which we made ourselves in cooperation with the Olympus Company, and how we use the technique in our hospital.     

Endoscopic submucosal dissection for colorectal neoplasms: A review

The introduction of colorectal endoscopic submucosal dissection(ESD)has expanded the application of endoscopic treatment,which can be used for lesions with a low metastatic potential regardless of their size.ESD has the advantage of achieving en bloc resection with a lower local recurrence rate compared with that of piecemeal endoscopic mucosal resection.Moreover,in the past,surgery was indicated in patients with large lesions spreading to almost the entire circumference of the rectum,regardless of the depth of invasion,as endoscopic resection of these lesions was technically difficult.Therefore,a prime benefit of ESD is significant improvement in the quality of life for patients who have large rectal lesions.On the other hand,ESD is not as widely applied in the treatment of colorectal neoplasms as it is in gastric cancers owing to the associated technical difficulty,longer procedural duration,and increased risk of perforation.To diversify the available endoscopic treatment strategies for superficial colorectal neoplasms,endoscopists performing ESD need torecognize its indications,the technical issues involved in its application,and the associated complications.This review outlines the methods and type of devices used for colorectal ESD,and the training required by endoscopists to perform this procedure.     

Training in endoscopic submucosal dissection from a Western perspective

Endoscopic submucosal dissection (ESD) is a mature endoscopic procedure that was developed in Japan to enable the en bloc, curative resection of superficial dysplastic lesions in the luminal gastrointestinal tract that have a low risk of lymph node metastasis. ESD requires a cognitive understanding of endosurgical principles, the ability to apply advanced optical imaging techniques to diagnose and stage lesions, and a high degree of endoscopic skill. Training in ESD should ideally begin with small lesions in the distal stomach, but such an approach is not applicable to endoscopists who are trying to learn and perform ESD in Western countries; as such, a “prevalence-based approach” is required that might vary from country to country. Proposed thresholds for attaining and maintaining competence in ESD, particularly for Western endoscopists, include rates of en bloc resection ≥80% and adverse events ≤10%. Endoscopists skilled in ESD should achieve rates of en bloc resection ≥90% and adverse events ≤5%. In order to offer ESD on a national level, a critical mass of endoscopists proficient in ESD is required who can then establish regional or national training centers and teach others with the requisite endoscopic skill and experience how to perform this elegant procedure. In the United States, ESD-specific billing codes are required to defray the procedural cost for endoscopy centers and health systems and to adequately compensate those endoscopists who offer this procedure as a life-saving alternative to more invasive surgical resection.     

磁锚定辅助牵引技术在食管早癌内镜黏膜下剥离术中应用的初步研究

目的目前,内镜黏膜下剥离术(ESD)已经成为消化道表浅癌的标准治疗方式,但对于食管病变,由于操作空间较为狭小,往往导致技术难度较大,手术耗时较长。本文报道了磁锚定牵引ESD治疗食管病变的初步结果。 方法2020年4月至2020年6月,共计5例食管浅表癌患者于解放军总医院第一医学中心接受磁锚定牵引ESD,前瞻性收集患者相关信息。 结果对于接受磁锚定牵引ESD的5例患者,整块切除率及完整切除率均为100%,R0切除率为80%,未见术中出血、术中穿孔、术后出血、术后穿孔等并发症发生。 结论初步研究结果证实,磁锚定牵引ESD治疗食管病变是安全可行的,但仍需进一步大样本的研究印证上述观点,并同时评估其长期有效性。