内镜黏膜下剥离术在治疗胃肠道黏膜切除术后残留和复发病灶中的应用

目的 探讨内镜黏膜下剥离术(ESD)治疗胃肠道黏膜切除术(EMR)后残留、复发病变的疗效和安全性.方法 自2006年6月至2007年11月对EMR术后内镜随访发现的15例残留和复发病变进行ESD治疗,先于黏膜下注射生理盐水以抬高病变,接着预切开病变周围黏膜,再沿病变下方黏膜下层进行剥离,对瘢痕形成部位直接应用Hook刀沿瘢痕基底切线方向进行切开.结果 15例EMR术后残留和复发病变,位于胃6例、结肠3例、直肠6例,病变直径0.8～3.5 cm,平均2.3 cm.所有病变抬举征(一).14例病变成功完成ESD治疗,成功率93.3%(14/15),13例术后病理切缘和基底无肿瘤累及,完整切除率86.7%(13/15).ESD手术时间60～155 min,平均87 min.治疗中创面均有少量出血,全组未出现术后出血.2例治疗中局部剥离较深、腹腔出现游离气体,成功保守治疗,未转外科手术,ESD穿孔发生率13.3%(2/15).术后平均随访13个月,无复发.结论 ESD治疗EMR术后残留和复发病变相对安全、有效,不仅能完整切除残留和复发病变,还能提供完整的病理诊断资料.     

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.     

Recent advances in endoscopic management of gastric neoplasms

The development and clinical application of new diagnostic endoscopic technologies such as endoscopic ultrasonography with biopsy, magnification endoscopy, and narrow-band imaging, more recently supplemented by artificial intelligence, have enabled wider recognition and detection of various gastric neoplasms including early gastric cancer (EGC) and subepithelial tumors, such as gastrointestinal stromal tumors and neuroendocrine tumors. Over the last decade, the evolution of novel advanced therapeutic endoscopic techniques, such as endoscopic mucosal resection, endoscopic submucosal dissection, endoscopic full-thickness resection, and submucosal tunneling endoscopic resection, along with the advent of a broad array of endoscopic accessories, has provided a promising and yet less invasive strategy for treating gastric neoplasms with the advantage of a reduced need for gastric surgery. Thus, the management algorithms of various gastric tumors in a defined subset of the patient population at low risk of lymph node metastasis and amenable to endoscopic resection, may require revision considering upcoming data given the high success rate of en bloc resection by experienced endoscopists. Moreover, endoscopic surveillance protocols for precancerous gastric lesions will continue to be refined by systematic reviews and meta-analyses of further research. However, the lack of familiarity with subtle endoscopic changes associated with EGC, as well as longer procedural time, evolving resection techniques and tools, a steep learning curve of such high-risk procedures, and lack of coding are issues that do not appeal to many gastroenterologists in the field. This review summarizes recent advances in the endoscopic management of gastric neoplasms, with special emphasis on diagnostic and therapeutic methods and their future prospects.     

Solutions for submucosal injection: What to choose and how to do it

During the past decades, endoscopic resection techniques have gradually improved and gained more importance for the management of premalignant lesions and early cancers. These endoscopic resection techniques can be divided in 3 major groups: snare polipectomy, endoscopic mucosal resection(EMR) and endoscopic submucosal dissection(ESD). The use of submucosal injection is essential for the majority of EMR techniques and is an integral part of ESD,whereas during polipectomy it is not crucial in most cases except to prevent bleeding in large polyps and/or those with large stalks as an alternative to mechanical methods. Injection provides a lifting up effect of the lesion separating it from the muscular layer, thereby reducing thermal injury and the risk of perforation and bleeding while also facilitating en-bloc resection by improving technical feasibility. With this work, we aim to review the most common endoscopic resection techniques and the importance of submucosal injection in each one of them. For that, we present some of the most commonly used submucosal injection solutions, taking into account their advantages and disadvantages. We also discuss, based on current recommendations and our own experience, how and when to preform submucosal injection, depending on lesions features and endoscopic resection technique that′s being used, to assure complete resection and to prevent associated adverse events. Finally, we also present and discuss some new proposed submucosal injection solutions,endoscopic resection techniques and devices that may have a major impact on the future of therapeutic endoscopy.     

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.     

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.     

Endoscopic submucosal dissection compared to endoscopic mucosal resection for early Barrett esophagus neoplasia

Endoscopic resection has become an invaluable diagnostic and therapeutic tool in the evaluation and management of early Barrett esophagus (BE) neoplasia. While endoscopic mucosal resection (EMR) is the current standard of care for the resection of nodular early BE neoplasia, endoscopic submucosal dissection (ESD) has been recently introduced as part of the armamentarium in the treatment of these lesions. The potential advantages of ESD compared to EMR include higher en-bloc and R0 resection rates, decreased local recurrence, and the procurement of large en-bloc specimens that may facilitate pathologic staging. On the other hand, EMR is less time-consuming and has been traditionally associated with a lower incidence of serious adverse events when compared to ESD. At present, the choice of the endoscopic resection technique hinges on operator’s preferences, patient and lesions characteristics and available local expertise. Future high-quality studies comparing clinical outcomes between ESD and EMR are needed to better define their roles in the management of early BE neoplasia.     

Benefits of endoscopic submucosal dissection according to size and location of gastric neoplasm, compared with conventional mucosal resection

Background and Aims:  To clarify optimal therapeutic strategies for early gastric cancers without vestigial remnant or recurrence, we evaluated the benefits of endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) according to tumor size and location.
Methods:  From January 2000 to December 2007, a total of 328 gastric lesions were treated using conventional EMR, while 572 lesions were treated by ESD. Patients who underwent surgery on the upper gastrointestinal tract before EMR or ESD were excluded from the study. We compared tumor size, location and rates of complete resection, curative resection, postoperative bleeding, perforation and local recurrence between EMR and ESD according to tumor situation.
Results:  Overall local complete resection rate (EMR, 64.2%; ESD, 95.1%) and overall curative resection rate (EMR, 59.5%; ESD, 82.7%) were significantly higher in ESD than in EMR. No significant differences were seen in complication rates between EMR and ESD. Local recurrence was detected in 13 lesions (4.0%) of the EMR group during follow up. In contrast, no local recurrence was detected in the ESD group. For lesions 5 mm or less in diameter, complete resection rate in the EMR group was not significantly inferior to that in the ESD group at any location. However, rates were overwhelmingly better in the ESD group than in the EMR group for lesions more than 5 mm in diameter, regardless of location.
Conclusion:  We concluded that lesions exceeding 5 mm in diameter should be treated by ESD, although a high resection rate is obtained also with EMR for lesions of 5 mm or less in diameter.     

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.     

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。     

Long-term Outcomes of Additional Endoscopic Treatments for Patients with Positive Lateral Margins after Endoscopic Submucosal Dissection for Early Gastric Cancer

Background/AimsIt is uncertain whether additional endoscopic treatment may be chosen over surgery in patients with positive lateral margins (pLMs) as the only non-curative factor after endoscopic submucosal dissection (ESD) for early gastric cancer (EGC). We aimed to compare the long-term outcomes of additional endoscopic treatments in such patients with those of surgery and elucidate the clinicopathological factors that could influence the treatment selection.MethodsA total of 99 patients with 101 EGC lesions undergoing additional treatment after non-curative ESD with pLMs as the only non-curative factor were analyzed. Among them, 25 (27 lesions) underwent ESD, 29 (29 lesions) underwent argon plasma coagulation (APC), and 45 (45 lesions) underwent surgery. Clinicopathological characteristics and long-term outcomes were compared.ResultsResidual tumor was found in 73.6% of cases. The presence of multiple pLMs was associated with higher risk of residual tumor (p=0.046). During a median follow-up of 58.9 months, recurrent or residual lesions after additional ESD and APC were found in 4% (1/25) and 6.8% (2/29) of patients, respectively. However, all were completely cured with surgery or repeated ESD. There were no extragastric recurrences after additional endoscopic treatment. Lymph node metastasis was identified after additional surgery in one (2.2%) patient with an EGC showing histological heterogeneity.ConclusionsGiven the favorable long-term outcomes, additional ESD or APC may be an acceptable choice for patients with pLMs as the only non-curative factor after ESD for EGC. However, clincopathological characteristics such as multiple pLMs and histological heterogeneity should be considered in the treatment selection.     

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.     

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.     

结直肠上皮性肿瘤内镜下切除技术的发展现状

热圈套器息肉切除术和内镜黏膜切除术是目前结直肠上皮性肿瘤内镜下治疗的标准方法,但仍伴有相当大概率的不良事件,由此诞生了诸如冷圈套器息肉切除术、内镜黏膜下剥离术、内镜全层切除术等新的内镜治疗技术,本文就目前结直肠上皮性肿瘤内镜切除技术方面取得的进展进行了综述。     

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.     

How can colorectal neoplasms be treated during colonoscopy？

AIM: For many physicians who ordinarily treat patients with colonic diseases, colonoscopy is considered a prime study interest. Developments in colonoscopic equipment and methods have led to a large number of endoscopic diagnoses and treatment for colorectal neoplasms. The purpose of this investigation is to evaluate the efficacy and outcomes of endoscopic treatment for colorectal neoplastic lesions. METHODS: From September 1999 to May 2003,11 447 consecutive colonoscopic examinations in 9 864 patients were gathered; totaling 5 502 endoscopic treatments for colorectal neoplasms. Macroscopic characteristics of the neoplasms were classified into protruded (n=3 953), sessile (n=1 402), lateral spreading tumor (n=139) and depressed lesions (n=8). Snare polypectomy was conducted in 3 984 lesions, hot forcep removal in 1 368 lesions, and endoscopic mucosal resection in 150 lesions. RESULTS: Histological diagnoses were 4 596 neoplastic lesions (4 376 adenomas and 220 adenocarcinomas) and 906 non-neoplastic lesions (891 hyperplastic and 15 inflammatory polyps). For the adenocarcinoma group, 31 instances involved submucosal invasion or resection margin, who received further operations, while 13 surgical specimens discovered no residual tumors. Three perforations and 96 bleedings were found following endoscopic treatment. No procedure-related mortality was found and no recurrent malignancy was found after 1456 mo follow-up. CONCLUSION: To lower the incidence and mortality of colorectal cancer, endoscopic treatment for colorectal neoplasms is a simple and safe procedure.     

Is Endoscopic Mucosal Resection a Sufficient Treatment for Low-Grade Gastric Epithelial Dysplasia?

Background/Aims

The rate of diagnosis of gastric adenoma has increased because esophagogastroduodenoscopy is being performed at an increasingly greater frequency. However, there are no treatment guidelines for low-grade dysplasia (LGD). To determine the appropriate treatment for LGD, we evaluated the risk factors associated with the categorical upgrade from LGD to high grade dysplasia (HGD)/early gastric cancer (EGC) and the risk factors for recurrence after endoscopic treatment.

Methods

We compared the complication rates, recurrence rates, and remnant lesions in 196 and 56 patients treated with endoscopic submucosal dissection (ESD) and endoscopic mucosal resection (EMR), respectively, by histologically confi rming low-grade gastric epithelial dysplasia.

Results

The en bloc resection rate was significantly lower in the EMR group (31.1%) compared with the ESD group (75.0%) (p<0.001). However, no significant difference was observed in the prevalence of remnant lesions or recurrence rate (p=0.911) of gastric adenoma. The progression of LGD to HGD or EGC caused an increase in the incidence of tumor lesions >1 cm with surface redness and depressions.

Conclusions

For the treatment of LGD, EMR resulted in a higher incidence of uncertain resection margins and a lower en bloc resection rate than ESD. However, there was no signifi cant difference in recurrence rate.     

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.