Endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) in 2011, a Western perspective

Endoscopic mucosal resection (EMR) has become the standard of care for removal of large flat and sessile neoplastic lesions of the GI tract. Recently, endoscopic submucosal dissection (ESD) was introduced in Japan as an alternative technique, which allows en bloc resection of large lesions. The applications of EMR and ESD are expanding and many Western endoscopists are adopting these techniques. Paris classification and Kudo pit pattern classification allows prediction of the depth of invasion of early neoplastic lesions and thus, avoids resection of lesions invading the deep submucosa which have higher rates of lymphatic spread. ESD of early stomach cancer is the standard of care in Japan. Recent published reports from Western countries showed comparable results for ESD of early gastric cancers to those done in Japan. Recently, EMR combined with ablation has been used frequently in Western countries for treatment of high-grade dysplasia in early adenocarcinoma of the esophagus. Although ESD of early neoplastic lesions of the esophagus is technically difficult, few promising reports were published proving the feasibility of this technique in the West. ESD has been shown to achieve higher en bloc resection and lower rates of tumour recurrence in removal of lateral spreading colonic polyps. A hybrid technique of circumferential submucosal incision followed by en bloc EMR has been used for removal of large colonic lesions in some Western endoscopy centres. In Western countries, training for ESD is challenging given the lack of training in the relatively easier early gastric cancer lesions. Animal model training combined with observing experts in ESD could be an alternative for Western endoscopists. Inspite of obstacles, ESD applications are continuing to grow in Western countries.     

Endoscopic submucosal dissection of early gastric cancer

Endoscopic mucosal resection (EMR) of early gastric cancer (EGC) without any risk of lymph node metastasis was developed in Japan in the 1980s, and it has been one of the standard treatments of EGC for nearly 20 years. Recently, several EMR techniques developed in Japan have been accepted and done in Western countries. These EMR techniques are safe and efficacious but unsuitable for large lesions. Because we could not remove a large lesion in 1 fragment, which was very important for the precise diagnosis of tumor depth, local recurrence increased in large-lesion cases. An innovative procedure using newly developed endoscopic knives, called endoscopic submucosal dissection (ESD), was developed in the late 1990s, which made it possible to remove a large lesion en bloc. Theoretically, ESD has no limitation with respect to tumor size; therefore, it is expected to replace the surgical treatment in some situations. Although ESD has spread throughout Japan within a short period, there remain several disadvantages, such as a higher incidence of complications and a requirement of higher endoscopic skills compared to those of conventional EMR methods. The endoscopic indications, procedures, complications and treatment outcomes of the ESD of EGC are described in this review.     

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.     

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.     

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.     

Do we have enough evidence for expanding the indications of ESD for EGC?

Endoscopic submucosal dissection(ESD) is the most advanced and representative technique in the field of therapeutic endoscopy and has been used for the treatment of gastrointestinal neoplasms,including early gastric cancer.The major difference and advantage of ESD compared to existing endoscopic resection techniques,such as endoscopic mucosal resection(EMR) and polypectomy,are the width and depth of the resection.Newly developed cutting devices,distal attachable endoscopic accessories,and an advanced electr...     

Endoscopic mucosal resection and endoscopic submucosal dissection for early gastric cancer: Current and original devices

Compared with endoscopic submucosal dissection (ESD), endoscopic mucosal resection (EMR) is easier to perform and requires less time for treatment. However, EMR has been replaced by ESD, because achieving en bloc resection of specimens > 20 mm in diameter is difficult with EMR. The technique of ESD was introduced to resect large specimens of early gastric cancer in a single piece. ESD can provide precise histological diagnosis and can also reduce the rate of recurrence, but has a high level of technical difficulty, and is consequently associated with a high rate of complications, a need for advanced endoscopic techniques, and a lengthy procedure time. To overcome disadvantages in both EMR and ESD, various advances have been made in submucosal injections, knives, other accessories, and in electrocoagulation systems.     

Endoscopic submucosal dissection for early gastric cancers: experience from a new endoscopic center in Taiwan

GOAL: To evaluate the efficacy of endoscopic submucosal dissection (ESD) for early gastric cancers (EGCs) at a new endoscopic center. BACKGROUND: ESD is a novel technique that can facilitate en-bloc resection of EGCs, but seldom reported outside Japan. STUDY: A total of 25 consecutive patients (25 lesions) underwent ESD from June 2004 to March 2006. Patients were divided into 2 groups: group A underwent ESD from June 2004 to May 2005 (introduction stage) and group B from June 2005 to March 2006. The following data were obtained: tumor size, tumor location, operative time, and major complication. RESULTS: The complete resection was achieved in 20 lesions (success rate 80%). Four out of 10 lesions from group A were removed by conventional endoscopic mucosal resection (EMR) piecemeally after ESD failure. Conversely, 14 patients from group B (n=15) were resected by ESD en-bloc (success rate 93.3%). One patient with microscopic residual tumor after ESD was further treated by surgical resection. The time required for resection was significantly longer in group A when compared with group B (130.5 min vs. 81.5 min, P<0.05). Postoperative complication rate between the 2 groups were similar. One patient with piecemeal EMR recurred in follow-up, and was further treated successfully by EMR. CONCLUSIONS: ESD is an ideal method for EGC treatment, but it may result in a risk of complication. The complete resection rate can be improved by endoscopist's experience. Sophisticated endoscopic hemostasis and clipping skills are essential prior ESD procedures. Conventional EMR techniques are also obligatory during the beginning period.     

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.     

Outcome after endoscopic submucosal dissection for early gastric cancer in Korea

Endoscopic treatment,such as endoscopic mucosal resection(EMR) and endoscopic submucosal dissection(ESD),has been established as one of the treatment options for selected cases with early gastric cancer(EGC).Most studies on this topic have been carried out by researchers in Japan.Recently,the experience in EMR/ESD for EGC outside Japan is increasingly reported.In Korea,gastric cancer is the most common malignant disease,and the second leading cause of cancer death.Currently,EMR for EGC is widely performed i...     

Rectal laterally spreading tumors successfully treated in two steps by endoscopic submucosal dissection and endoscopic mucosal resection

Background  

Endoscopic submucosal dissection (ESD) is an advanced technique of therapeutic endoscopy alternative to endoscopic mucosal resection (EMR) for superficial gastrointestinal neoplasms >2 cm. ESD allows for the direct dissection of the submucosa and large lesions can be resected en bloc. ESD is not limited by resection size, increases histologically complete resection rates and may reduce the local recurrence.     

Endoscopic submucosal dissection for gastrointestinal neoplasms

Endoscopic submucosal dissection （ESD） is an advanced technique of therapeutic endoscopy for superficial gastrointestinal neoplasms. Three steps characterize it：injecting fluid into the submucosa to elevate the lesion, cutting the surrounding mucosa of the lesion, and dissecting the submucosa beneath the lesion. The ESD technique has rapidly permeated in Japan for treatment of early gastric cancer, due to its excellent results of en- bloc resection compared to endoscopic mucosal resection （EMR）. Although there is still room for improvement to lessen its technical difficulty, ESD has recently been applied to esophageal and colorectal neoplasms. Favorable short-term results have been reported, but the application of ESD should be well considered by three aspects：（1） the possibility of nodal metastases of the lesion, （2） technical difficulty such as location, ulceration and operator＇s skill, and （3） organ characteristics.     

Endoscopic resection for early gastric cancer: current status in Korea

Endoscopic mucosal resection (EMR) was introduced in the 1990s, and endoscopic submucosal dissection (ESD) in 2003. Currently, ESD is becoming the main procedure for the resection of early gastric cancer (EGC), and provides safer and curative outcomes. Endoscopic resection (ER) showed excellent long-term survival in Korea. The number of ESD has doubled over 5 years. ESD might be better than EMR in terms of en bloc resection, complete resection and long-term outcome. Novel techniques including endoscopic full-thickness resection with lymph node dissection will be positioned for some EGC.     

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.     

Endoscopic resection of superficial gastrointestinal tumors

Therapeutic endoscopy plays a major role in the management of gastrointestinal （GI） neoplasia. Its indications can be generalized into four broad categories; to remove or obliterate neoplastic lesion, to palliate malignant obstruction, or to treat bleeding. Only endoscopic resection allows complete histological staging of the cancer, which is critical as it allows stratification and refinement for further treatment. Although other endoscopic techniques, such as ablation therapy, may also cure early GI cancer, they can not provide a definitive pathological specimen. Early stage lesions reveal low frequency of lymph node metastasis which allows for less invasive treatments and thereby improving the quality of life when compared to surgery. Endoscopic mucosal resection （EMR） and endoscopic submucosal dissection （ESD） are now accepted worldwide as treatment modalities for early cancers of the GI tract.     

Endoscopic submucosal dissection for early gastric cancer

Endoscopic mucosal resection (EMR) has been accepted as a treatment of early gastric cancer (EGC). The number of EMR procedures for EGC has been increasing because a patient's quality of life after EMR is superior to that after surgical gastrectomy. In Japan, most EMR have been performed using the strip biopsy method; however, in some cases we experienced local recurrences when multiple fragments had been resected by this method. Single-fragment resection is preferable for correct histological diagnosis and a patient's prognosis. Recently, dramatic changes have occurred in the operational technique and design of the accessory apparatus. In 1996, we developed a special endoscopic knife, called the insulation-tipped electrosurgical knife (IT knife), which consists of a conventional diathermic needle knife with a ceramic ball at the top to minimize the risk of perforation. This knife can cut submucosa safely and remove a lesion completely. We named this method endoscopic submucosal dissection (ESD). Using this procedure, 96% of the tumors (471/488) were completely resected in one piece. During the follow-up period, there were no recurrent cases. One-piece resection by ESD using the IT knife improves the quality of life and prognosis for patients with early gastric cancer.     

Endoscopic mucosal resection and endoscopic submucosal dissection of epithelial neoplasia of the colon

Endoscopic mucosal resection (EMR) with curative intent has evolved into a safe and effective technique and is currently the gold standard for management of large colonic epithelial neoplasms. Piecemeal EMR is associated with a high risk of local recurrence requiring vigilant surveillance and repeat interventions. Endoscopic submucosal dissection (ESD) was introduced in Japan for the management of early gastric cancer, and has recently been described for en bloc resection of colonic lesions greater than 20 mm. En bloc resection allows accurate histological assessment of the depth of invasion, minimizes the risk of local recurrence and helps determine additional therapy. Morphologic classification of lesions prior to resection allows prediction of depth of invasion and risk of nodal metastasis, allowing selection of the appropriate intervention. This review provides an overview of the assessment of epithelial neoplasms of the colon and the application of EMR and ESD techniques in their management.     

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 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 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.