Anis Ahmadi, Peter Draganov, Division Gastroenterology Hepatology and Nutrition, University of Florida, Gainesville, Florida 32610, United States

Author contributions: Ahmadi A and Draganov P contributed equally to this work.

Correspondence to: Peter Draganov, Dr, Division Gastroenterology Hepatology and Nutrition, University of Florida, Gainesville, 1600 SW Archer Road PO Box 100214, Florida 32610, United States. dragapv@medicine.ufl.edu

Telephone: +1-352-3922877    Fax: +1-352-3923618

Received: December 15, 2007  Revised: January 31, 2008

Abstract

Endoscopic mucosal resection (EMR) is a technique used to locally excise lesions confined to the mucosa. Its main role is the treatment of advanced dysplasia and early gastrointestinal cancers. EMR was originally described as a therapy for early gastric cancer. Recently its use has expanded as a therapeutic option for ampullary masses, colorectal cancer, and large colorectal polyps. In the Western world, the predominant indication for EMR in the upper gastrointestinal tract is the staging and treatment of advance dysplasia and early neoplasia in Barrett’s esophagus. This review will describe the basis, indications, techniques, and complications of EMR, and its role in the management of Barrett’s esophagus.

© 2008 WJG. All rights reserved.

Key words: Endoscopic mucosal resection; Mucosal resection; Barrett’s esophagus; Barrett’s dysplasia; Therapeutic endoscopy

Peer reviewer: Ryuichi Iwakiri, Dr, Department of Medicine and Gastrointestinal Endoscopy, Saga Medical School, 5-1-1 Nabeshima, Saga 849-8501, Japan

Ahmadi A, Draganov P. Endoscopic mucosal resection in the upper gastrointestinal tract. World J Gastroenterol 2008; 14(13): 1984-1989  Available from URL: http://www.wjgnet.com/1007-9327/14/1984.asp  DOI: http://dx.doi.org/10.3748/wjg.14.1984

INTRODUCTION

Endoscopic mucosal resection (EMR) is a technique used to locally excise lesions confined to the mucosa. Its main role in therapeutic endoscopy is the treatment of advanced dysplasia and early gastrointestinal (GI) cancers^[1-4]. Tada et al published the first case report of EMR in 1984 as a treatment option for early-stage gastric carcinoma^[5]. Since then, EMR has been used diagnostically and therapeutically in both the upper and lower GI tracts, and has significantly lower morbidity and mortality compared to surgical management^[6].

EMR is most commonly used to locally treat early gastric and esophageal dysplasia/cancer. However, there are several reports describing EMR as a therapeutic option for ampullary masses, colorectal cancer, and large colorectal polyps^[7-10]. In the Western world, the predominant indication for EMR in the upper GI tract is the staging and treatment of early neoplasia in Barrett’s esophagus. This review will describe the basis, indications, techniques, and complications of EMR, and its role in the management of Barrett’s esophagus.

BASIS OF EMR

The GI wall is comprised of 5 layers: mucosa, deep mucosa, submucosa, muscularis propria, and serosa or adventitia. The two major components are the mucosal and the muscular layer. The submucosa consists of loose connective tissue that attaches the above layers together. The mucosal and muscular layers can be separated from each other by injection of fluid into the submucosal layer. This allows for safe resection of mucosal lesions without causing damage of the deeper muscle layer^[11].

EMR has become standard practice because of its following distinct advantages: (1) advanced dysplasia and most early neoplastic lesions are free of lymph-node metastases, and can be treated with curative intent simply by local resection^[12]; (2) EMR provides tissue specimen for histology and staging^[13]; (3) EMR is minimally invasive and carries lower morbidity and mortality compared to traditional surgical approaches^[14]; and (4) surgery can be performed after EMR if advanced neoplasia or incomplete resection is detected on histologic evaluation of the EMR specimen.

EMR also has some disadvantages: (1) EMR is labor intense, time consuming, and requires advanced endoscopic skills; (2) larger lesions can only be resected in piecemeal fashion which precludes evaluation for completeness of the resection at the lateral margins; (3) there is uncertainty regarding the long term outcome of patients treated with EMR due to the lack of randomized trials directly comparing EMR with surgery; and (4) EMR is poorly reimbursed in the US.

TECHNIQUES OF EMR

Once a mucosal lesion is identified, it is helpful to perform chromoendoscopy ± endoscopic ultrasound to further define the size and borders of the lesion, and determine its depth of invasion^[15-17]. Both chromoendoscopy and narrow band imaging can help improve detection of dysplastic lesions, and further delineate the borders of the lesion. Additionally, computer tomography (CT) imaging can help determine the size of the lesion and rule out distant metastatic disease prior to proceeding with EUS. Although it can be challenging to determine intramucosal from submucosal neoplasias, the risk of pre-existing lymph node metastases must be discussed with the patient prior to pursuing EMR. Ultimately, histopathologic evaluation of the EMR specimen is the most important predictor of lymph node metastasis. Surgical management of early esophageal/gastric malignancies should be based on the histological analysis of the EMR specimen (i.e. depth of invasion) as well as each patient’s surgical morbidity and mortality risks.

Several EMR techniques have been described in the literature. Multiple EMR techniques are available: (1) strip-off biopsy; (2) “inject, lift, and cut” method; (3) the “cup and suction” or EMR-cap technique; and lastly (4) EMR with band ligation^[18]. Prior to pursuing any of the above methods, it is recommended that the periphery of the lesion be marked with either a needle knife, electrocautery, or argon plasma coagulator (APC). This allows for distinct identification of the borders of the lesion that is being excised. The absence of all markings assists in determining if the resection is complete.

Depending on the EMR technique used, lift injection may be required. No standardization of the type of injection solution exists. Various injectates that have been used include normal saline, normal saline plus epinephrine solution, 50% dextrose in normal saline, 10% glycerine/5% fructose in normal saline, hyaluronic acid, and a mixture of methylene blue and normal saline^[18,19]. Injection of these various solutions can help lift the mucosa from the submucosa, and theoretically decrease the risk of perforation and reduce the risk of hemorrhage^[20]. An additional advantage of injecting prior to EMR is identification of lesions that do not successfully lift, which generally suggests involvement of the submucosal layer, and thus are not candidates for resection^[15].

Multiple electrosurgical currents are used during EMR, including blend, cut, and coagulation settings, depending primarily on operator preference. The electrosurgical setting most commonly used in the esophagus at Leeds is the ERBE “endo-cut mode” with a power setting of 45 watts^[21]. In a recent editorial by Seewald et al, a pure coagulation current with the Erbotom at a setting 3- and 60-W output was used for electrosurgical resection^[22].

(1) The strip biopsy is the least complex EMR technique, but is often limited to polypoid or nodular lesions only^[23]. It is similar to standard polypectomy. Injection into the submucosa is not done. A diathermy snare is tightened around a lesion, which is subsequently removed with the application of an electrical cutting current. The strip biopsy technique can be applied to flat lesions by using either a barbed snare or ultra stiff snare^[24].

(2) The “inject, lift, and cut” method is similar to the strip-off method. A two channel upper endoscope is needed. Prior to snaring the lesion, a submucosal injection is used to effectively lift the mucosa from the submucosa, thereby potentially reducing the risk of perforating the muscular layer. The lesion is then lifted by forceps and situated into a snare (via the second channel of a dual-channel endoscope), such that the lesion is resected at the base by applying electrocautery^[20].

(3) The “cup and suction” or EMR-cap technique is the most frequently used method of EMR in the esophagus^[25]. This technique was first described by Inohue et al in 1993^[26]. This method requires a transparent plastic cap be attached to the distal tip of a single-channel endoscope. This is followed by injection of approximately 20 mL of lifting solution into the submucosa. A designated “duck bill” small-diameter snare is then placed within the rim of the transparent cap. Following this, the lesion is sucked into the cap as the snare is closed at the base of the lesion. Once suction has been released and it has been determined that the entire lesion is contained within the snare, the lesion is removed using electrocautery^[27].

The advantages of the EMR-cap technique are that a standard single-channel endoscope can be used, and only one endoscopy assistant is required. In addition, it appears that there is a lower risk of bleeding compared to the strip-off method^[21,25]. The disadvantage is that it may be difficult to ensure that the entire lesion has been aspirated into the cap, and occasionally, visualization of the lesion can be obscured by the cap itself. Furthermore, the snare tends to loose its shape after a single use and thus a new snare is usually required for each piece of tissue removed. This can quickly add to the cost of the procedure, particularly if a large surface area needs to be removed (e.g. long segment Barrett’s esophagus).

(4) EMR with ligation is similar to the EMR-cap technique, in that suction of the lesion is required. However, unlike the EMR-cap technique, the lesion is suctioned into a ligation cylinder without prior submucosal injection. A rubber band is then deployed at the base to create a pseudopolyp. The pseudopolyp is subsequently removed at its base by tightening a snare just below the level of the rubber band^[28]. The standard band ligator can be used, but a designated ligator that fits the single channel therapeutic upper scope is available (Duette, Cook Medical, Winston-Salem, NC). The main disadvantage of this technique with the standard ligator is that the endoscope must be withdrawn to remove the ligation cylinder before reinsertion for resection^[29]. The Duette system, on the other hand, allows the passage of a snare via the therapeutic channel of the scope and multiple resections can be carried out sequentially without the need of removing the scope.

The EMR-cap and EMR with ligation techniques have been prospectively compared to each other in a single-center study performed by May A et al. In this study, 50 EMR-cap resections were compared to 50 EMR with ligation resections of early stage esophageal cancer. No significant difference in the maximal diameter of the resection specimen area was noted between the two groups. In addition, only one minor episode of bleeding was seen in each group, with no severe complications in either group. Therefore, it was concluded that both techniques are similar in efficacy and safety^[30].

ENDOSCOPIC SUBMUCOSAL DISSECTION (ESD)

ESD, one of the more recently described techniques, has been developed to perform single en-block resections of large mucosal lesions^[31]. This technique involves the use of an electrocautery knife to dissect out mucosal lesions. Several knives have been developed for ESD, including triangle-tip knives, hook knives, insulation-tip knives, and flex knives^[32-34]. In ESD with use of a triangle-tip knife, the borders of a mucosal lesion are marked by electrocautery and then injection of an epinephrine-saline solution into the submucosa is performed. This is followed by marginal cutting circumferentially, via electrocautery, around the previous markings. At this point, a high-viscosity solution (such as hyaluronic acid) is injected to provide a longer period of mucosal lifting to allow for actual submucosal dissection. Dissection is carried out by electro cauterization using the tip of the triangle-tip knife to free the mucosal lesion from the submucosa. Once completed, the freed mucosa is removed^[27]. At present, the various knives used for ESD are not available in the US.

EMR COMPLICATIONS

As with any endoscopic procedure, complication rates are operator dependent and diminish with increased experience. The Japanese Society of Gastrointestinal Endoscopy calculated a complication rate of 0.5% based on all upper GI EMR’s performed between 1993 to 1997^[35]. A lower overall complication rate of 0.17% was reported by Kaneko et al in 1995. The mortality rate calculated by Kaneko et al was 0.0001%^[36].

The risks of EMR include bleeding, pain, perforation, and stricture formation. Bleeding can occur at the time of the procedure, or be delayed for up to 12 h. Bleeding rarely occurs beyond 24 h after the procedure. Venous oozing is more common following esophageal EMR, whereas brisk bleeding is more common after gastric EMR of large and fundic lesions. Bleeding is most commonly treated endoscopically via electrocauterization, APC, or placement of metallic clips^[37-40].

Dull pain following EMR generally results from denudation of the mucosa and subsequent exposure to gastric acid. This pain can often be controlled by proton-pump inhibitors. Sudden sharp pain, especially during or at the completion of the procedure, should raise suspicion of a perforation^[41]. The risk of perforation following EMR of gastric lesions is 0.06%-5%^[42]. Upper GI tract perforation can be managed conservatively with the combination of clipping, nasogastric tube suction, and broad-spectrum antibiotics^[43].

Patients are at an increased risk of developing strictures if circumferential resections of the esophagus or gastric pylorus are performed^[29,44,45]. These strictures are often responsive to dilation. To date, animal studies have not identified that prophylactic balloon dilation, esophageal stenting, or deep mural steroid injections prevent the formation of strictures^[44].

INDICATIONS FOR EMR IN THE UPPER GI TRACT

Gastric malignancy

Per the Japanese literature, the indications for EMR in resection of superficial gastric cancers applies to well- or moderately differentiated adenocarcinoma and/or papillary carcinoma. Gastric cancers that penetrate the submucosa are at increased risk of lymph node metastases. Gastric cancer confined to the mucosa has a 0%-5% risk of lymph node metastases, compared to 10%-20% risk if the cancer involves the submucosa^[46-49]. Thus, gastric lesions must meet the following criteria to be candidates for EMR: confined to the mucosa, < 2 cm for elevated lesions, < 1 cm for flat or depressed lesions, cannot be associated with an ulcer or ulcer scar, and cannot have venous or lymphatic involvement^[50].

Esophageal squamous cell carcinoma

Currently, EMR is generally indicated for superficial well- or moderately differentiated squamous cell carcinoma without venous or lymphatic involvement that is limited to the lamina propria. This is based on a 0% risk of metastasis when the neoplasia is limited to the epithelium, compared to the 12% and 26% risk of metastasis when the neoplasia involves the muscularis mucosa and submucosa, respectively^[51]. There is no consensus on the maximum size of the lesion that can be resected. EMR is not recommended for circumferential lesions secondary to the risk of subsequent stricture formation^[15].

High-grade dysplasia and early adenocarcinoma in Barrett’s esophagus (BE)

BE is associated with a 30-fold increased risk of esophageal adenocarcinoma, which remains one of most rapidly rising cancers in the Western world^[52-54]. Although EMR has a clear role in squamous cell carcinoma, its role in BE is not clearly defined, although studies have determined that EMR is effective in removing visible lesions in BE^[24,30,55]. In fact, current evidence suggests that EMR of high-grade dysplasia (HGD) and early cancer (EC) has similar success rates as surgical treatment^[56-60]. According to Ell et al, the indications for EMR in the setting of Barrett’s neoplasia include the following: lesions limited to the mucosa that are macroscopically flat, tumor size between 20-30 mm, and good to moderate differentiation on histology^[56]. Additionally, research suggests that EMR has better diagnostic reproducibility compared to mucosal biopsies alone, implying a possible role in routine surveillance^[61]. Certainly, the cost-effectiveness and availability of EMR would need to be considered prior to pursuing EMR as a primary tool in the surveillance of BE.

In one of the largest studies evaluating the efficacy of EMR for treatment of HGD and EC, 97% complete remission was achieved in resection of “low-risk” lesions and 59% complete remission in resection of “high-risk” lesions. “Low-risk” lesions were defined as macroscopic lesions measuring up to 20 mm and limited to the mucosa. However, at an average 12 mo follow-up period, the combined recurrence and metachronous cancer rate was 14%^[56]. In an Italian study, EMR was found to be an effective method of treating HGD and intramucosal cancer in 34 patients that did not have submucosal involvement, with all patients remaining in remission at a median follow-up of 34.9 mo. In addition, EMR changed the pretreatment diagnosis in 25.6% of the studied patients^[62].

Recurrence of neoplastic disease after EMR is a potential limitation^[56,59]. Therefore, circumferential resection, in which the targeted dysplastic lesion and the surrounding Barrett’s mucosa are removed, has also been studied^[63]. In two separate studies from 2003 and 2006, no recurrent or metachronous lesions were reported. This is in stark contrast to an 11% recurrence rate with circumferential resections at a mean follow-up of 18 mo in a study by Giovannini et al^[24,29,55].

In addition to EMR, multiple ablative techniques have been evaluated in the management of HGD and EC in BE. These include photodynamic therapy (PDT), argon beam coagulation therapy, lasers, radiofrequency ablation, and yttrium-aluminum-garnet laser therapy^[64-68]. In fact, a recently-published multicenter, randomized controlled trial has shown that photodynamic therapy with Photofrin is superior than omeprazole alone in eliminating HGD at 5 years follow-up (77% vs 39%, respectively)^[69]. To improve eradication of neoplastic tissue and decrease recurrence rates, the combined use of EMR with ablative techniques have been described^[59,70]. Theoretically, recurrence rates are expected to be much lower with combined modalities, because both visible and non-visible lesions would be eradicated.

Combined modality has been evaluated by the Wiesbaden group in two separate studies. In the first study, 28 patients underwent EMR, 13 underwent PDT, 3 underwent APC, and 6 patients received a combination of these therapies for the treatment of HGD or EC. Metachronous or recurrent lesions were seen in 23% of the patients at a mean follow-up period of 34 ± 10 mo. Amongst the patients treated with EMR alone, 6/28 patients (21.4%) developed metachronous or recurrent lesions, compared to 1/6 patients (16.6%) treated with combined modalities^[59]. In a follow-up study of a total of 115 patients (EMR = 70, PDT = 32, APC = 3, EMR + PDT = 10) undergoing endoscopic treatment for HGD or EC, there was a 31% rate of metachronous or recurrent lesions over an average follow-up time of 34 ± 10 mo. Individually, the metachronous or recurrence rate was 30% (21/70) in the EMR group vs 37.5% in the EMR + PDT group^[70]. It is important to note that the number of patients treated with the combined modality is markedly less than that treated with EMR alone.

Conclusion

Since its introduction as a potential treatment option of GI mucosal cancers in 1984, the indications for EMR are continuing to expand. Today, EMR has become an integral part of the therapeutic endoscopy armamentarium. Although there are no specific guidelines for EMR as a treatment option for HGD or early cancer in Barrett’s esophagus, the literature indicates that EMR is similar to surgery in efficacy, but has less morbidity and mortality. As newer techniques of EMR, including circumferential mucosectomy, are developed, the potential of reducing recurrence and metachronous rates are inviting.

REFERENCES

1         Nigro JJ, Hagen JA, DeMeester TR, DeMeester SR, Theisen J, Peters JH, Kiyabu M. Occult esophageal     adenocarcinoma: extent of disease and implications for effective therapy. Ann Surg 1999; 230: 433-438; discussion     438-440 PubMed

2         Nigro JJ, Hagen JA, DeMeester TR, DeMeester SR, Peters JH, Oberg S, Theisen J, Kiyabu M, Crookes PF, Bremner CG.     Prevalence and location of nodal metastases in distal esophageal adenocarcinoma confined to the wall: implications     for therapy. J Thorac Cardiovasc Surg 1999; 117: 16-23; discussion 23-25 PubMed

3         Ruol A, Merigliano S, Baldan N, Santi S, Petrin GF, Bonavina L, Ancona E, Peracchia A. Prevalence, management and     outcome of early adenocarcinoma (pT1) of the esophago-gastric junction. Comparison between early cancer in     Barrett's esophagus (type I) and early cancer of the cardia (type II). Dis Esophagus 1997; 10: 190-195 PubMed

4         Stein HJ, Feith M, Mueller J, Werner M, Siewert JR. Limited resection for early adenocarcinoma in Barrett's     esophagus. Ann Surg 2000; 232: 733-742 PubMed

5         Tada M, Shimada M, Murakami F. Development of the strip-off biopsy. Gastroenterol Endosc 1984; 26: 833-839

6         Yokota T, Sugihara K, Yoshida S. Endoscopic mucosal resection for colorectal neoplastic lesions. Dis Colon Rectum     1994; 37: 1108-1111 PubMed

7         Takahashi M, Minabe D, Kotani A, Kito F, Koganei K, Fukushima T. Successful resection of ampullary carcinoma in a     father and adenoma in a daughter with familial adenomatous polyposis following detection by surveillance: report of     two cases. Surg Today 2001; 31: 1100-1103 PubMed

8         Mukai M, Ito I, Mukoyama S, Okamoto Y, Sugimoto M, Tsuchiya K, Sato S, Nakasaki H, Makuuchi H. Endoscopic     mucosal resection of superficially spreading colonic neoplasms larger than 5 cm in the right colon after injection of     dilute sodium hyaluronate: report of two cases. Endoscopy 2003; 35: 973-974 PubMed

9         Jameel JK, Pillinger SH, Moncur P, Tsai HH, Duthie GS. Endoscopic mucosal resection (EMR) in the management of     large colo-rectal polyps. Colorectal Dis 2006; 8: 497-500 PubMed

10      Kudo S. Endoscopic mucosal resection of flat and depressed types of early colorectal cancer. Endoscopy 1993; 25:   455-461 PubMed

11      Rosenberg N. Submucosal saline wheal as safety factor in fulguration or rectal and sigmoidal polypi. AMA Arch Surg    1955; 70: 120-122 PubMed

12      Stein HJ, Feith M. Surgical strategies for early esophageal adenocarcinoma. Best Pract Res Clin Gastroenterol 2005;    19: 927-940 PubMed

13      Vieth M, Ell C, Gossner L, May A, Stolte M. Histological analysis of endoscopic resection specimens from 326 patients    with Barrett's esophagus and early neoplasia. Endoscopy 2004; 36: 776-781 PubMed

14      Fernando HC, Luketich JD, Buenaventura PO, Perry Y, Christie NA. Outcomes of minimally invasive esophagectomy      

         (MIE) for high-grade dysplasia of the esophagus. Eur J Cardiothorac Surg 2002; 22: 1-6 PubMed

15      Soetikno R, Kaltenbach T, Yeh R, Gotoda T. Endoscopic mucosal resection for early cancers of the upper    gastrointestinal tract. J Clin Oncol 2005; 23: 4490-4498 PubMed

16      Rosch T. Endosonographic staging of esophageal cancer: a review of literature results. Gastrointest Endosc Clin N Am    1995; 5: 537-547 PubMed

17      Falk GW, Catalano MF, Sivak MV Jr, Rice TW, Van Dam J. Endosonography in the evaluation of patients with Barrett's    esophagus and high-grade dysplasia. Gastrointest Endosc 1994; 40: 207-212 PubMed

18      Conio M, Cameron AJ, Chak A, Blanchi S, Filiberti R. Endoscopic treatment of high-grade dysplasia and early cancer in    Barrett's oesophagus. Lancet Oncol 2005; 6: 311-321 PubMed

19      Conio M, Rajan E, Sorbi D, Norton I, Herman L, Filiberti R, Gostout CJ. Comparative performance in the porcine    esophagus of different solutions used for submucosal injection. Gastrointest Endosc 2002; 56: 513-516 PubMed

20      Gossner L. The role of endoscopic resection and ablation therapy for early lesions. Best Pract Res Clin Gastroenterol    2006; 20: 867-876 PubMed

21      Rembacken BJ, Gotoda T, Fujii T, Axon AT. Endoscopic mucosal resection. Endoscopy 2001; 33: 709-718 PubMed

22      Seewald S, Omar S, Soehendra N. Endoscopic mucosectomy of the esophagus. Am J Gastroenterol 2007; 102: 236-   238 PubMed

23      Soehendra N, Binmoeller KF, Bohnacker S, Seitz U, Brand B, Thonke F, Gurakuqi G. Endoscopic snare mucosectomy in    the esophagus without any additional equipment: a simple technique for resection of flat early cancer. Endoscopy    1997; 29: 380-383 PubMed

24      Seewald S, Akaraviputh T, Seitz U, Brand B, Groth S, Mendoza G, He X, Thonke F, Stolte M, Schroeder S, Soehendra    N. Circumferential EMR and complete removal of Barrett's epithelium: a new approach to management of Barrett's    esophagus containing high-grade intraepithelial neoplasia and intramucosal carcinoma. Gastrointest Endosc 2003; 57:    854-859 PubMed

25      Tanabe S, Koizumi W, Kokutou M, Imaizumi H, Ishii K, Kida M, Yokoyama Y, Ohida M, Saigenji K, Shimao H, Mitomi H.    Usefulness of endoscopic aspiration mucosectomy as compared with strip biopsy for the treatment of gastric mucosal    cancer. Gastrointest Endosc 1999; 50: 819-822 PubMed

26      Inoue H, Takeshita K, Hori H, Muraoka Y, Yoneshima H, Endo M. Endoscopic mucosal resection with a cap-fitted    panendoscope for esophagus, stomach, and colon mucosal lesions. Gastrointest Endosc 1993; 39: 58-62 PubMed

27      Inoue H, Sato Y, Sugaya S, Inui M, Odaka N, Satodate H, Kudo SE. Endoscopic mucosal resection for early-stage    gastrointestinal cancers. Best Pract Res Clin Gastroenterol 2005; 19: 871-877 PubMed

28      Nwakakwa V, Fleischer D. Endoscopic mucosal resection of the esophagus: band ligation technique. Gastrointest   Endosc Clin N Am 2001; 11: 479-488, vi PubMed

29      Soehendra N, Seewald S, Groth S, Omar S, Seitz U, Zhong Y, de Weerth A, Thonke F, Schroeder S. Use of modified   multiband ligator facilitates circumferential EMR in Barrett's esophagus (with video). Gastrointest Endosc 2006; 63: 847-   852 PubMed

30      May A, Gossner L, Behrens A, Kohnen R, Vieth M, Stolte M, Ell C. A prospective randomized trial of two different    endoscopic resection techniques for early stage cancer of the esophagus. Gastrointest Endosc 2003; 58: 167-175

         PubMed

31      Ohkuwa M, Hosokawa K, Boku N, Ohtu A, Tajiri H, Yoshida S. New endoscopic treatment for intramucosal gastric    tumors using an insulated-tip diathermic knife. Endoscopy 2001; 33: 221-226 PubMed

32      Ono H, Kondo H, Gotoda T, Shirao K, Yamaguchi H, Saito D, Hosokawa K, Shimoda T, Yoshida S. Endoscopic mucosal    resection for treatment of early gastric cancer. Gut 2001; 48: 225-229 PubMed

33      Yamamoto H, Yube T, Isoda N, Sato Y, Sekine Y, Higashizawa T, Ido K, Kimura K, Kanai N. A novel method of    endoscopic mucosal resection using sodium hyaluronate. Gastrointest Endosc 1999; 50: 251-256 PubMed

34      Hosokawa K, Yoshida S. Recent advances in endoscopic mucosal resection for early gastric cancer. Gan To Kagaku   Ryoho 1998; 25: 476-483 PubMed

35      Kaneko E, Hanada H, Kasugai T, Sakita T. The survey of gastrointestinal endoscopic complications in Japan (1993-   1997, in Japanese). Gastroenterol Endosc 2000; 42: 308-313

36      Kaneko E, Harada H, Kasugai T, Sakita T. The results of a multi-center analysis from 1988-1992 (in Japanese).   Gastroenterol Endosc 1995; 37: 642-652

37      Fujishiro M, Ono H, Gotoda T, Yamaguchi H, Kondo H, Saito D. Usefulness of Maalox for detection of the precise    bleeding points and confirmation of hemostasis on gastrointestinal hemorrhage. Endoscopy 2001; 33: 196 PubMed

38      Szaloki T, Toth V, Tiszlavicz L, Czako L. Flat gastric polyps: results of forceps biopsy, endoscopic mucosal resection,    and long-term follow-up. Scand J Gastroenterol 2006; 41: 1105-1109 PubMed

39      Fujishiro M, Yahagi N, Nakamura M, Kakushima N, Kodashima S, Ono S, Kobayashi K, Hashimoto T, Yamamichi N,    Tateishi A, Shimizu Y, Oka M, Ichinose M, Omata M. Safety of argon plasma coagulation for hemostasis during    endoscopic mucosal resection. Surg Laparosc Endosc Percutan Tech 2006; 16: 137-140 PubMed

40      Peters FP, Kara MA, Rosmolen WD, Aalders MC, Ten Kate FJ, Bultje BC, Krishnadath KK, Fockens P, van Lanschot JJ,    van Deventer SJ, Bergman JJ. Endoscopic treatment of high-grade dysplasia and early stage cancer in Barrett's    esophagus. Gastrointest Endosc 2005; 61: 506-514 PubMed

41      Soetikno RM, Gotoda T, Nakanishi Y, Soehendra N. Endoscopic mucosal resection. Gastrointest Endosc 2003; 57: 567-   579 PubMed

42      Tada M. One piece resection and piecemeal resection of early gastric cancer by strip biopsy. Tokyo: Igaku-Shoin,    1998: 68-87

43      Takeshita K, Tani M, Inoue H, Saeki I, Hayashi S, Honda T, Kando F, Saito N, Endo M. Endoscopic treatment of early    oesophageal or gastric cancer. Gut 1997; 40: 123-127 PubMed

44      Rajan E, Gostout C, Feitoza A, Herman L, Knipschield M, Burgart L, Chung S, Cotton P, Hawes R, Kalloo A, Kantsevoy S,    Pasricha P. Widespread endoscopic mucosal resection of the esophagus with strategies for stricture prevention: a    preclinical study. Endoscopy 2005; 37: 1111-1115 PubMed

45      Katada C, Muto M, Manabe T, Boku N, Ohtsu A, Yoshida S. Esophageal stenosis after endoscopic mucosal resection of    superficial esophageal lesions. Gastrointest Endosc 2003; 57: 165-169 PubMed

46      Moreaux J, Bougaran J. Early gastric cancer. A 25-year surgical experience. Ann Surg 1993; 217: 347-355 PubMed

47      Perri F, Iuliano R, Valente G, Angelillo IF, Arrigoni A, Campra D, Recchia S, Andriulli A. Minute and small early gastric    cancers in a Western population: a clinicopathologic study. Gastrointest Endosc 1995; 41: 475-480 PubMed

48      Baba H, Maehara Y, Okuyama T, Orita H, Anai H, Akazawa K, Sugimachi K. Lymph node metastasis and macroscopic    features in early gastric cancer. Hepatogastroenterology 1994; 41: 380-383 PubMed

49      Endo M, Habu H. Clinical studies of early gastric cancer. Hepatogastroenterology 1990; 37: 408-410 PubMed

50      Tsujitani S, Oka S, Saito H, Kondo A, Ikeguchi M, Maeta M, Kaibara N. Less invasive surgery for early gastric cancer    based on the low probability of lymph node metastasis. Surgery 1999; 125: 148-154 PubMed

51      Kodama M, Kakegawa T. Treatment of superficial cancer of the esophagus: a summary of responses to a    questionnaire on superficial cancer of the esophagus in Japan. Surgery 1998; 123: 432-439 PubMed

52      Brown LM, Devesa SS. Epidemiologic trends in esophageal and gastric cancer in the United States. Surg Oncol Clin N    Am 2002; 11: 235-256 PubMed

53      Devesa SS, Blot WJ, Fraumeni JF Jr. Changing patterns in the incidence of esophageal and gastric carcinoma in the    United States. Cancer 1998; 83: 2049-2053 PubMed

54      Falk GW. Barrett's esophagus. Gastroenterology 2002; 122: 1569-1591 PubMed

55      Giovannini M, Bories E, Pesenti C, Moutardier V, Monges G, Danisi C, Lelong B, Delpero JR. Circumferential endoscopic    mucosal resection in Barrett's esophagus with high-grade intraepithelial neoplasia or mucosal cancer. Preliminary    results in 21 patients. Endoscopy 2004; 36: 782-787 PubMed

56      Ell C, May A, Gossner L, Pech O, Gunter E, Mayer G, Henrich R, Vieth M, Muller H, Seitz G, Stolte M. Endoscopic    mucosal resection of early cancer and high-grade dysplasia in Barrett's esophagus. Gastroenterology 2000; 118: 670-   677 PubMed

57      Ciocirlan M, Lapalus MG, Hervieu V, Souquet JC, Napoleon B, Scoazec JY, Lefort C, Saurin JC, Ponchon T. Endoscopic    mucosal resection for squamous premalignant and early malignant lesions of the esophagus. Endoscopy 2007; 39: 24-   29 PubMed

58      Esaki M, Matsumoto T, Hirakawa K, Nakamura S, Umeno J, Koga H, Yao T, Iida M. Risk factors for local recurrence of    superficial esophageal cancer after treatment by endoscopic mucosal resection. Endoscopy 2007; 39: 41-45 PubMed

59      May A, Gossner L, Pech O, Fritz A, Gunter E, Mayer G, Muller H, Seitz G, Vieth M, Stolte M, Ell C. Local endoscopic    therapy for intraepithelial high-grade neoplasia and early adenocarcinoma in Barrett's oesophagus: acute-phase and    intermediate results of a new treatment approach. Eur J Gastroenterol Hepatol 2002; 14: 1085-1091 PubMed

60      Ell C, May A, Pech O, Gossner L, Guenter E, Behrens A, Nachbar L, Huijsmans J, Vieth M, Stolte M. Curative endoscopic    resection of early esophageal adenocarcinomas (Barrett's cancer). Gastrointest Endosc 2007; 65: 3-10 PubMed

61      Mino-Kenudson M, Hull MJ, Brown I, Muzikansky A, Srivastava A, Glickman J, Park DY, Zuckerberg L, Misdraji J, Odze   RD, Lauwers GY. EMR for Barrett's esophagus-related superficial neoplasms offers better diagnostic reproducibility than   mucosal biopsy. Gastrointest Endosc 2007; 66: 660-666; quiz 767, 769 PubMed

62      Conio M, Repici A, Cestari R, Blanchi S, Lapertosa G, Missale G, Della Casa D, Villanacci V, Calandri PG, Filiberti R.    Endoscopic mucosal resection for high-grade dysplasia and intramucosal carcinoma in Barrett's esophagus: an Italian    experience. World J Gastroenterol 2005; 11: 6650-6655 PubMed

63      Seewald S, Ang TL, Soehendra N. Endoscopic mucosal resection of Barrett's oesophagus containing dysplasia or    intramucosal cancer. Postgrad Med J 2007; 83: 367-372 PubMed

64      Barham CP, Jones RL, Biddlestone LR, Hardwick RH, Shepherd NA, Barr H. Photothermal laser ablation of Barrett's    oesophagus: endoscopic and histological evidence of squamous re-epithelialisation. Gut 1997; 41: 281-284 PubMed

65      Dumoulin FL, Terjung B, Neubrand M, Scheurlen C, Fischer HP, Sauerbruch T. Treatment of Barrett's esophagus by    endoscopic argon plasma coagulation. Endoscopy 1997; 29: 751-753 PubMed

66      Attwood SE, Lewis CJ, Caplin S, Hemming K, Armstrong G. Argon beam plasma coagulation as therapy for high-grade    dysplasia in Barrett's esophagus. Clin Gastroenterol Hepatol 2003; 1: 258-263 PubMed

67      Weston AP, Sharma P. Neodymium:yttrium-aluminum garnet contact laser ablation of Barrett's high grade dysplasia    and early adenocarcinoma. Am J Gastroenterol 2002; 97: 2998-3006 PubMed

68      Panjehpour M, Overholt BF, Haydek JM, Lee SG. Results of photodynamic therapy for ablation of dysplasia and early    cancer in Barrett's esophagus and effect of oral steroids on stricture formation. Am J Gastroenterol 2000; 95: 2177-   2184 PubMed

69      Overholt BF, Wang KK, Burdick JS, Lightdale CJ, Kimmey M, Nava HR, Sivak MV Jr, Nishioka N, Barr H, Marcon N,    Pedrosa M, Bronner MP, Grace M, Depot M. Five-year efficacy and safety of photodynamic therapy with Photofrin in    Barrett's high-grade dysplasia. Gastrointest Endosc 2007; 66: 460-468 PubMed

70      May A, Gossner L, Pech O, Muller H, Vieth M, Stolte M, Ell C. Intraepithelial high-grade neoplasia and early    adenocarcinoma in short-segment Barrett's esophagus (SSBE): curative treatment using local endoscopic treatment    techniques. Endoscopy 2002; 34: 604-610 PubMed

                    S- Editor  Li DL    L- Editor  Rippe RA    E- Editor  Liu Y

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