- Email: [email protected]
Endoscopic Mucosal Resection of the Esophagus
ENDOSCOPY MUCOSAL RESECTION
1052-5157 /01 $15.00 + .00
ENDOSCOPIC MUCOSAL RESECTION OF THE ESOPHAGUS Band Ligation Technique Victor Nwakakwa, MD, MRCP(UK), and David Fleischer, MD, MACP
Endoscopic mucosal resection (EMR) is a minimally invasive endoscopic technique used in treating superficial cancers or premalignant lesions in the gastrointestinal (GI) tract. It has been more widely used in Japan and a few other countries in the East than in the West. An attraction of this technique is that it can be curative with low morbidity, often providing the entire lesion for pathologic evaluation. Several techniques of EMR have been described: strip biopsy; lift and cut (these two are also known as free hand mucosectomy); the Makuuchi tube method; cap ligation; and band ligation.1, 3, 5, 8, 9, i2, 15-17, 20 This article discusses the band ligation technique. There are two variant band ligating devices in the literature,1· 3• 8• 13• 15 and both are described because there are slight differences in the techniques. INDICATIONS FOR ENDOSCOPIC MUCOSAL RESECTON
There are three reasons for removal of lesions in the GI tract: (1) suspicion of malignancy or malignant potential, (2) for histologic diagnosis, and (3) for treatment of symptoms. An example of EMR being used because of the suspicion of malignancy or malignant potential is a distal esophageal lesion in a patient with Barrett's esophagus. In this case histology is critical because it affects the management. On some occasions EMR is useful for histologic diagnosis. For example, the distinction between a granular cell From the Division of Gastroenterology, Georgetown University Medical Center, Washington, DC
GASTROINTESTINAL ENDOSCOPY CLINICS OF NORTH AMERICA VOLUME 11 •NUMBER 3 • JULY 2001
479
480
NWAKAKWA & FLEISCHER
tumor and a squamous papilloma may require tissue removal. An example of treatment for symptoms is a non-neoplastic polyp in the GI tract that causes bleeding. Resection is indicated if amenable to this form of treatment (EMR). One should consider EMR for any lesion amenable to that mode of treatment for the reasons reiterated here: it retrieves tissue but is not ablative, facilitating histologic diagnosis, and it is minimally invasive with low morbidity and proved efficacy. The lesions for which EMR should be considered are discussed under the following headings: esophageal, gastric, and colonic. When EMR is used with curative intent for neoplastic disease, the lesion must have the following characteristics: (1) be superficial to the muscularis propria to avoid perforation on removal; (2) be noncircumferential to avoid the late complication of stenosis; (3) be superficial to the lymphatics and small vessels of the submucosa to minimize failure to achieve cure because of inapparent metastasis; and (4) should ideally have a surface area small enough for en bloc resection (a diameter of 20 mm or less).10, 12 ESOPHAGEAL LESIONS
Dysplastic areas in patients at risk for squamous cell cancer and similar areas within a Barrett's esophagus, early esophageal carcinomas, and nodules or flat lesions constitute the major lesions for which EMR is used. These may be visible as nodular or polypoid lesions or plaques but often may not be macroscopically identifiable, as in many cases identified on surveillance biopsies of Barrett's esophagus. The value of chromoendoscopy in improving the identification of these less visible lesions is discussed later. GASTRIC LESIONS
Endoscopic mu cosa! resection has been used extensively by the Japanese in the treatment of early gastric cancer. "Early" is defined as the limitation of invasion to the mucosa or submucosa. There are three main types in the Japanese classification: type I, protruding; type II, flat; and type III, depressed. Type II is further divided into a, b, and c (elevated, flat, and depressed, respectively). The diagnosis is usually in a screening program or incidental because patients are asymptomatic. Other potential uses for EMR include adenomatous polyps and gastric carcinoids. COLONIC LESIONS
Pedunculated polyps are easily removed in the colon with standard snare cautery. The difficulty arises with the flat adenomatous polyps, which
ENDOSCOPIC MUCOSAL RESECTION OF THE ESOPHAGUS
481
usually need to be elevated with saline injection. It seems that it is in this group that the general technique of EMR can be applied.
CHROMOENDOSCOPY AND ENDOSCOPIC MUCOSAL RESECTION
Chromoendoscopy is the endoscopic use of vital staining to improve the definition and localization of mucosal lesions. If used in conjunction with EMR it has the potential to improve the curative potential of the latter, by defining the pathologic process or delineating the margins. Four vital stains have been used most commonly for clinical purposes in the esophagus: (1) methylene blue, (2) Lugol's iodine, (3) toluidine blue, and (4) indigo carmine. 2 The first three are absorptive stains, whereas indigo carmine is a contrast stain. Methylene blue is taken up by actively absorbing intestinaltype cells and is useful in Barrett's esophagus, where it stains specialized columnar epithelium but not gastric-type or squamous epithelium. Lugol' s iodine stains glycogen-containing squamous cells and is useful in identifying dysplasia or squamous cell cancer, which do not stain because of depleted glycogen content. It may also be of marginal use in Barrett's esophagus where it delineates squamous from columnar epithelium (the latter does not stain). Toluidine blue stains nuclei of columnar cells but not squamous cells and is useful in identifying Barrett's esophagus, which stains, and squamous cell cancer, which does not stain. Indigo carmine is a nonabsorbed stain, which when used with magnification endoscopy may make subtle mucosal irregularities more prominent and may be useful in Barrett's esophagus.
EVALUATION BEFORE ENDOSCOPIC MUCOSAL RESECTION
Endoscopic ultrasound evaluation of the lesion to be endoscopically resected is wise before EMR to confirm its superficial nature. Highfrequency ultrasound probe (20 MHz) is well suited for this purpose. Involvement of the muscularis propria is generally regarded as a contraindication to EMR because of the high risk of perforation in those circumstances. Penetration beyond the superficial third of the submucosa is also regarded as a relative contraindication because the risk of regional lymph node involvement becomes significant. 4 This risk differs in different regions of the GI tract for similar degrees of tumor penetration. The risk is 0% to 5% when disease is limited to the mucosa.7· 11 It increases to 30% to 50% with penetration into the submucosa for esophageal cancer but only increases to 15% to 25% for gastric cancer and 10% to 15% for rectal cancer. 4 Some have suggested that this approach makes EMR safer.6, 13, 14
482
NWAI
TECHNIQUE OF ENDOSCOPIC MUCOSAL RESECTION BAND LIGATION
In general the EMR band ligating device involves the use of equipment similar to that for endoscopic variceal band ligation. The technique involves the use of (1) a standard endoscope, (2) a banding device, and (3) usually an overtube. Routine sedation is used. In the technique described a few years ago3 the endoscope is introduced with an overtube because the procedure may require three passes of the endoscope to complete. The lesion is identified and may then be delineated by spraying a dye (indigo carmine or iodine) in the esophagus to identify the glycogen-depleted abnormal areas (Fig. lA). Because the dye fades after 5 to 10 minutes, it is often valuable to make two to four electrocautery markings on its borders to aid targeting of the lesion. A submucosal injection of 10 to 50 mL of normal saline is given to separate the mucosa from the submucosa and create a cushion (Fig. 1 B). Other solutions have been used, such as 50% dextrose, saline and dilute epinephrine, sodium hyaluronate, and all these with chromoendoscopic dyes. There are no comparative studies to suggest that one is better than the others. Some, however, have suggested that sodium hyaluronate resulted in a more clearly delineated and durable pseudopolyp. 18, 19 After the submucosal injection, the endoscope is withdrawn and fitted at the distal end with a friction adaptor for ligation that has been preloaded with a rubber band. The endoscope is then reintroduced through the overtube into the esophagus. When the lesion is identified from previous staining or cautery marks, it is suctioned into the ligator device and the rubber band is deployed (Fig. lC). The endoscope is again withdrawn, the ligator device removed, and the endoscope reinserted. The polyp created by the rubber band is inspected to ensure that it contains the lesion to be resected. It is then ensnared with an electrocautery snare just above the rubber band and removed using a coagulation current as for standard polypectomy (Figs. 1 D and 2). Retrieval is carried out by suctioning the polyp to the endoscope tip or by using the Roth basket or grasping forceps. A variant of this method was described by Akiyama et al. 1 They used a pneumoactivated ligating device that consisted of an air feeding tube, a sliding tube, an inner cylinder, and a rubber band (0-ring). The deployment of the rubber band is achieved by pumping through the air feeding tube, which makes the sliding tube slide on an inner cylinder on which the rubber band lies thereby slipping it off. An endoscope is introduced with an overtube, the lesion marked with a dye or electrocautery, and a pseudopolyp created as in the previous technique. The endoscope is then withdrawn and fitted with the ligating device and reinserted. The lesion is again suctioned into the ligating device and the rubber band deployed as described previously. An electrocautery snare is introduced through the biopsy channel of the endoscope without withdrawal and the pseudopolyp snared with coagulation current. This
ENDOSCOPIC MUCOSAL RESECTION OF THE ESOPHAGUS
483
technique involves one less introduction of the endoscope than the previous technique. The use of the ligating technique of EMR is evident in serial reports in the literature. 1• 3• 8• 15• 20 A summary of the results is presented in Table 1. In the report by Akiyama et al1 there were 27 patients with 40 lesions resected (9 early gastric cancers and 31 gastric adenomas). The mean size of resected specimens was 14.2 x 13.6 mm (range from 12 x 12 to 18 x 18 mm). All lesions of 12 mm or less in size were completely resected in a single procedure. Lesions of 14 mm or more needed a repeat procedure. All 40 lesions were completely resected without any complications, such as perforation or massive bleeding. In the report by Suzuki et al1 5 there were a total of 37 patients with 40 lesions (17 early gastric cancers and 23 gastric adenomas) and the average size of resected specimens was 12.8 x 11 mm. The rate of complete resection including piecemeal resections was 100% for antral lesions, 80% at the angularis, 61.1 % in the body, and 0% in the cardia. No serious complications of perforation or hemorrhage were noted. The article by Lee et al 8 describes four cases in which band ligation was used. All patients had minute gastric cancers. All lesions were completely removed. The size of resected specimens ranged from 10 to 15 mm. The time required for removal of each specimen was less than 15 minutes. No major complications were reported. In the report by Yokoyama et al, 20 there were four patients. All had early gastric cancers. Three (75%) of four were completely resected. The one not completely resected was said to have had scar formation because of prior biopsy. The band ligation technique was reportedly simple and quick taking only 40 minutes on the average to perform. In the authors' previous report3 the first part of the study involved four mongrel dogs. A total of 19 tissue specimens was obtained varying from 12 to 15 mm. One perforation was reported. This was the largest of all the specimens (15 x 10 x 8 mm) . In the second part of the study (human studies) there were five patients with early esophageal cancers or dysplasia. The technique was successful in all cases, although one patient required two sessions for complete resection. In two of the patients the margin of resection specimen showed dysplasia, although on follow-up endoscopies with the same technique no residual neoplastic tissue was found. Hemorrhage was reported in one of the patients and hemostasis achieved by cautery; also, the specimen was not retrieved in this patient because of this complication. There are no direct comparisons between the band ligation and other EMR techniques. The advantages of this technique are as follows. (1) It uses a technique (banding) with which most GI endoscopists are familiar. (2) It is easier for difficult locations like lesser curvature of the stomach, posterior wall, and cardia of the stomach. 1 (3) It also affords the endoscopist a second chance after deploying the rubber band to review the pseudopolyp before resection. The rubber band can be removed and replaced if there is any doubt that it contains the entire lesion or if it seems to contain too much tissue with possible increased risk of complications. 13 (4) It uses a standard
484
NWAKAKWA & FLEISCHER
A
B Figure 1. EMR-band ligation technique. A , Spraying mucosa! surface helps identify and delineate the mucosa! abnormality. B, Lesion before and after submucosal injection.
ENDOSCOPIC MUCOSAL RESECTION OF THE ESOPHAGUS
485
c
D Figure 1 (Continued). C, Tissue is suctioned into cap and band applied. 0, Banded lesion before and after mucosectomy.
486
NWAKAKWA & FLEISCHER
Figure 2. Endoscopic view of lesion after banding (left) and after mucosectomy (right) .
endoscope, not the two-channel endoscope required in some of the other techniques. The disadvantages of this technique are that (1) it requires several intubations with and without the overtube, and (2) en bloc resected specimens are usually 12 mm or less. 1 The major complications of EMR band ligation are bleeding and perforation. 3 As mentioned previously there are no direct comparisons of the complication rates with other techniques in the literature. It seems likely that these complications are less related to the individual EMR technique than the nature, size, and location of the lesion that is being resected, and the experience of the endoscopist. The area in which EMR has been used effectively is in curative treatment of early cancers and premalignant lesions. It not only provides a less invasive treatment option than conventional surgery but also is able to provide en bloc tissue containing the entire lesion for histologic evaluation, the latter being its advantage over other less invasive options like photodynamic therapy, or thermal devices that ablate the lesion without providing histologic samples. It is more commonly used in Japan and other countries in the East where the incidence of gastric and esophageal cancer is high and elaborate screening programs are being carried out. It is becoming more common in the West, however, where it should find acceptance in treatment of early esophageal cancers or dysplastic esophageal lesions identified for example on patients with Barrett's esophagus who undergo screening.
Table 1. RATE OF COMPLETE RESECTION AND MAJOR COMPLICATIONS OF EMR- BAND LITIGATION Number of Patients
Number of Lesions
Akiyama
27
40
Suzuki
37
40
4 4 (dogs) 5 (patients) 4
4 19 5 4
Lee Fleischer Yokoyama
""
00 'I
Histology
9 early gastric cancer 31 gastric adenomas 23 adenomas 17 carcinomas All adenocarcinoma N/A Moderate dysplasia All were early gastric cancers
Mean Size of Specimens Resected
Rate of Complete Resection
Major Complications
14.2 x 13.6 mm
100%
None
12.8 x 11 mm
100% antrum 80% angle 61 .1% body 0% cardia 75% 100% 60% 75%
None
10-15 mm (range) 12- 15 mm (range) Not available Not available
None 1 perforation 5.3% 1 bleeding 20% Not available
488
NWAKAKWA & FLEISCHER
References 1. Akiyama M, Ota M, Nakajima H, et al: Endoscopic mucosa! resection of gastric neoplasms using a ligating device. Gastrointest Enclose 45:182-186, 1997 2. Canto MI: Vital staining and Barrett's esophagus. Gastrointest Enclose 49:S12-16, 1999 3. Fleischer DE, Wang G, Dawsey S, et al: Tissue band ligation followed by snare resection (band and snare): A new technique for tissue acquisition in the esophagus. Gastrointest Enclose 44:68-72, 1996 4. Giovannini M, Bernardini D, Moutardier V, et al: Endoscopic mucosa! resection (EMR): Results and prognostic factors in 21 patients. Endoscopy 31:698- 701, 1999 5. Inoue H, Tani M, Nagai K, et al: Treatment of esophageal and gastric tumors. Endoscopy 31:47-55, 1999 6. Izumi Y, Inoue H, Kawano T, et al: Endosonography during endoscopic mucosa! resection to enhance its safety: A new technique. Surg Enclose 13:358-360, 1999 7. Lambert R: Endoscopic mucosectomy: An alternative treatment for superficial esophageal cancer. Recent Results Cancer Res 155:183-192, 2000 8. Lee DK, Lee SW, Kwon SO, et al: Endoscopic mucosectomy using an esophageal variceal ligation device for minute gastric cancer. Endoscopy 28:386-389, 1996 9. Makuuchi H, Kise Y, Shimada H, et al: Endoscopic mucosa! resection for early gastric cancer. Semin Surg Oncol 17:108-116, 1999 10. Ninomiya Y, Yanagisawa A, Kato Y, et al: Unrecognizable intramucosal spread of diffusetype mucosa! gastric carcinomas of less than 20 mm in size. Endoscopy 32:604-608, 2000 11. Roukos DH: Current status and future perspectives in gastric cancer management. Cancer Treat Rev 26:243-255, 2000 12. Sadahiro S, Ishida H, Tokunaga N, et al: Experimental assessment of endoscopic mucosectomy with a cap-fitted panendoscope. Endoscopy 30:713-717, 1998 13. Shikuwa S, Matsunaga K, Osabe M, et al: Esophageal granular cell tumor treated by endoscopic mucosa! resection using a ligating device. Gastrointest Enclose 47:529-531, 1998 14. Souquet JC, Napoleon B, Pujol B, et al: Echoendoscopy prior to endoscopic tumor therapy: More safety? Endoscopy 25:475-478, 1993 15. Suzuki Y, Hiraishi H, Kanke K, et al: Treatment of gastric tumors by endoscopic mucosa! resection with a ligating device. Gastrointest Enclose 49:192-198, 1999 16. Tanabe S, Koizumi W, KokutouM, et al: Usefulness of endoscopic aspiration mucosectomy as compared with strip biopsy for the treatment of gastric mucosa! cancer. Gastrointest Enclose 50:819-822, 1999 17. Waxman I, Saitoh Y: Clinical outcome of endoscopic mucosa! resection for superficial GI lesions and the role of high-frequency US probe sonography in an American population. Gastrointest Enclose 52:322-327, 2000 18. Yamamoto H, Koiwai H, Yube T, et al: A successful single-step endoscopic resection of a 40 millimeter flat-elevated tumor in the rectum: Endoscopic mucosa! resection using sodium hyaluronate. Gastrointest Enclose 50:701-704, 1999 19. Yamamoto H, Yube T, Isoda N, et al: A novel method of endoscopic mucosa! resection using sodium hyaluronate. Gastrointest Enclose 50:251-256, 1999 20. Yokoyama T, Usui K, Tsujimoto M, et al: A new endoscopic resection technique for early gastric cancer, using an endoscopic ligating device designed to treat esophageal varices:preliminary report of four cases. Endoscopy 27:283, 1995
Address reprint requests to David Fleischer, MD, MACP Division of Gastroenterology Georgetown University Medical Center Rm2122 Washington, DC 20007 e-mail: [email protected]
1052-5157 /01 $15.00 + .00
ENDOSCOPIC MUCOSAL RESECTION OF THE ESOPHAGUS Band Ligation Technique Victor Nwakakwa, MD, MRCP(UK), and David Fleischer, MD, MACP
Endoscopic mucosal resection (EMR) is a minimally invasive endoscopic technique used in treating superficial cancers or premalignant lesions in the gastrointestinal (GI) tract. It has been more widely used in Japan and a few other countries in the East than in the West. An attraction of this technique is that it can be curative with low morbidity, often providing the entire lesion for pathologic evaluation. Several techniques of EMR have been described: strip biopsy; lift and cut (these two are also known as free hand mucosectomy); the Makuuchi tube method; cap ligation; and band ligation.1, 3, 5, 8, 9, i2, 15-17, 20 This article discusses the band ligation technique. There are two variant band ligating devices in the literature,1· 3• 8• 13• 15 and both are described because there are slight differences in the techniques. INDICATIONS FOR ENDOSCOPIC MUCOSAL RESECTON
There are three reasons for removal of lesions in the GI tract: (1) suspicion of malignancy or malignant potential, (2) for histologic diagnosis, and (3) for treatment of symptoms. An example of EMR being used because of the suspicion of malignancy or malignant potential is a distal esophageal lesion in a patient with Barrett's esophagus. In this case histology is critical because it affects the management. On some occasions EMR is useful for histologic diagnosis. For example, the distinction between a granular cell From the Division of Gastroenterology, Georgetown University Medical Center, Washington, DC
GASTROINTESTINAL ENDOSCOPY CLINICS OF NORTH AMERICA VOLUME 11 •NUMBER 3 • JULY 2001
479
480
NWAKAKWA & FLEISCHER
tumor and a squamous papilloma may require tissue removal. An example of treatment for symptoms is a non-neoplastic polyp in the GI tract that causes bleeding. Resection is indicated if amenable to this form of treatment (EMR). One should consider EMR for any lesion amenable to that mode of treatment for the reasons reiterated here: it retrieves tissue but is not ablative, facilitating histologic diagnosis, and it is minimally invasive with low morbidity and proved efficacy. The lesions for which EMR should be considered are discussed under the following headings: esophageal, gastric, and colonic. When EMR is used with curative intent for neoplastic disease, the lesion must have the following characteristics: (1) be superficial to the muscularis propria to avoid perforation on removal; (2) be noncircumferential to avoid the late complication of stenosis; (3) be superficial to the lymphatics and small vessels of the submucosa to minimize failure to achieve cure because of inapparent metastasis; and (4) should ideally have a surface area small enough for en bloc resection (a diameter of 20 mm or less).10, 12 ESOPHAGEAL LESIONS
Dysplastic areas in patients at risk for squamous cell cancer and similar areas within a Barrett's esophagus, early esophageal carcinomas, and nodules or flat lesions constitute the major lesions for which EMR is used. These may be visible as nodular or polypoid lesions or plaques but often may not be macroscopically identifiable, as in many cases identified on surveillance biopsies of Barrett's esophagus. The value of chromoendoscopy in improving the identification of these less visible lesions is discussed later. GASTRIC LESIONS
Endoscopic mu cosa! resection has been used extensively by the Japanese in the treatment of early gastric cancer. "Early" is defined as the limitation of invasion to the mucosa or submucosa. There are three main types in the Japanese classification: type I, protruding; type II, flat; and type III, depressed. Type II is further divided into a, b, and c (elevated, flat, and depressed, respectively). The diagnosis is usually in a screening program or incidental because patients are asymptomatic. Other potential uses for EMR include adenomatous polyps and gastric carcinoids. COLONIC LESIONS
Pedunculated polyps are easily removed in the colon with standard snare cautery. The difficulty arises with the flat adenomatous polyps, which
ENDOSCOPIC MUCOSAL RESECTION OF THE ESOPHAGUS
481
usually need to be elevated with saline injection. It seems that it is in this group that the general technique of EMR can be applied.
CHROMOENDOSCOPY AND ENDOSCOPIC MUCOSAL RESECTION
Chromoendoscopy is the endoscopic use of vital staining to improve the definition and localization of mucosal lesions. If used in conjunction with EMR it has the potential to improve the curative potential of the latter, by defining the pathologic process or delineating the margins. Four vital stains have been used most commonly for clinical purposes in the esophagus: (1) methylene blue, (2) Lugol's iodine, (3) toluidine blue, and (4) indigo carmine. 2 The first three are absorptive stains, whereas indigo carmine is a contrast stain. Methylene blue is taken up by actively absorbing intestinaltype cells and is useful in Barrett's esophagus, where it stains specialized columnar epithelium but not gastric-type or squamous epithelium. Lugol' s iodine stains glycogen-containing squamous cells and is useful in identifying dysplasia or squamous cell cancer, which do not stain because of depleted glycogen content. It may also be of marginal use in Barrett's esophagus where it delineates squamous from columnar epithelium (the latter does not stain). Toluidine blue stains nuclei of columnar cells but not squamous cells and is useful in identifying Barrett's esophagus, which stains, and squamous cell cancer, which does not stain. Indigo carmine is a nonabsorbed stain, which when used with magnification endoscopy may make subtle mucosal irregularities more prominent and may be useful in Barrett's esophagus.
EVALUATION BEFORE ENDOSCOPIC MUCOSAL RESECTION
Endoscopic ultrasound evaluation of the lesion to be endoscopically resected is wise before EMR to confirm its superficial nature. Highfrequency ultrasound probe (20 MHz) is well suited for this purpose. Involvement of the muscularis propria is generally regarded as a contraindication to EMR because of the high risk of perforation in those circumstances. Penetration beyond the superficial third of the submucosa is also regarded as a relative contraindication because the risk of regional lymph node involvement becomes significant. 4 This risk differs in different regions of the GI tract for similar degrees of tumor penetration. The risk is 0% to 5% when disease is limited to the mucosa.7· 11 It increases to 30% to 50% with penetration into the submucosa for esophageal cancer but only increases to 15% to 25% for gastric cancer and 10% to 15% for rectal cancer. 4 Some have suggested that this approach makes EMR safer.6, 13, 14
482
NWAI
TECHNIQUE OF ENDOSCOPIC MUCOSAL RESECTION BAND LIGATION
In general the EMR band ligating device involves the use of equipment similar to that for endoscopic variceal band ligation. The technique involves the use of (1) a standard endoscope, (2) a banding device, and (3) usually an overtube. Routine sedation is used. In the technique described a few years ago3 the endoscope is introduced with an overtube because the procedure may require three passes of the endoscope to complete. The lesion is identified and may then be delineated by spraying a dye (indigo carmine or iodine) in the esophagus to identify the glycogen-depleted abnormal areas (Fig. lA). Because the dye fades after 5 to 10 minutes, it is often valuable to make two to four electrocautery markings on its borders to aid targeting of the lesion. A submucosal injection of 10 to 50 mL of normal saline is given to separate the mucosa from the submucosa and create a cushion (Fig. 1 B). Other solutions have been used, such as 50% dextrose, saline and dilute epinephrine, sodium hyaluronate, and all these with chromoendoscopic dyes. There are no comparative studies to suggest that one is better than the others. Some, however, have suggested that sodium hyaluronate resulted in a more clearly delineated and durable pseudopolyp. 18, 19 After the submucosal injection, the endoscope is withdrawn and fitted at the distal end with a friction adaptor for ligation that has been preloaded with a rubber band. The endoscope is then reintroduced through the overtube into the esophagus. When the lesion is identified from previous staining or cautery marks, it is suctioned into the ligator device and the rubber band is deployed (Fig. lC). The endoscope is again withdrawn, the ligator device removed, and the endoscope reinserted. The polyp created by the rubber band is inspected to ensure that it contains the lesion to be resected. It is then ensnared with an electrocautery snare just above the rubber band and removed using a coagulation current as for standard polypectomy (Figs. 1 D and 2). Retrieval is carried out by suctioning the polyp to the endoscope tip or by using the Roth basket or grasping forceps. A variant of this method was described by Akiyama et al. 1 They used a pneumoactivated ligating device that consisted of an air feeding tube, a sliding tube, an inner cylinder, and a rubber band (0-ring). The deployment of the rubber band is achieved by pumping through the air feeding tube, which makes the sliding tube slide on an inner cylinder on which the rubber band lies thereby slipping it off. An endoscope is introduced with an overtube, the lesion marked with a dye or electrocautery, and a pseudopolyp created as in the previous technique. The endoscope is then withdrawn and fitted with the ligating device and reinserted. The lesion is again suctioned into the ligating device and the rubber band deployed as described previously. An electrocautery snare is introduced through the biopsy channel of the endoscope without withdrawal and the pseudopolyp snared with coagulation current. This
ENDOSCOPIC MUCOSAL RESECTION OF THE ESOPHAGUS
483
technique involves one less introduction of the endoscope than the previous technique. The use of the ligating technique of EMR is evident in serial reports in the literature. 1• 3• 8• 15• 20 A summary of the results is presented in Table 1. In the report by Akiyama et al1 there were 27 patients with 40 lesions resected (9 early gastric cancers and 31 gastric adenomas). The mean size of resected specimens was 14.2 x 13.6 mm (range from 12 x 12 to 18 x 18 mm). All lesions of 12 mm or less in size were completely resected in a single procedure. Lesions of 14 mm or more needed a repeat procedure. All 40 lesions were completely resected without any complications, such as perforation or massive bleeding. In the report by Suzuki et al1 5 there were a total of 37 patients with 40 lesions (17 early gastric cancers and 23 gastric adenomas) and the average size of resected specimens was 12.8 x 11 mm. The rate of complete resection including piecemeal resections was 100% for antral lesions, 80% at the angularis, 61.1 % in the body, and 0% in the cardia. No serious complications of perforation or hemorrhage were noted. The article by Lee et al 8 describes four cases in which band ligation was used. All patients had minute gastric cancers. All lesions were completely removed. The size of resected specimens ranged from 10 to 15 mm. The time required for removal of each specimen was less than 15 minutes. No major complications were reported. In the report by Yokoyama et al, 20 there were four patients. All had early gastric cancers. Three (75%) of four were completely resected. The one not completely resected was said to have had scar formation because of prior biopsy. The band ligation technique was reportedly simple and quick taking only 40 minutes on the average to perform. In the authors' previous report3 the first part of the study involved four mongrel dogs. A total of 19 tissue specimens was obtained varying from 12 to 15 mm. One perforation was reported. This was the largest of all the specimens (15 x 10 x 8 mm) . In the second part of the study (human studies) there were five patients with early esophageal cancers or dysplasia. The technique was successful in all cases, although one patient required two sessions for complete resection. In two of the patients the margin of resection specimen showed dysplasia, although on follow-up endoscopies with the same technique no residual neoplastic tissue was found. Hemorrhage was reported in one of the patients and hemostasis achieved by cautery; also, the specimen was not retrieved in this patient because of this complication. There are no direct comparisons between the band ligation and other EMR techniques. The advantages of this technique are as follows. (1) It uses a technique (banding) with which most GI endoscopists are familiar. (2) It is easier for difficult locations like lesser curvature of the stomach, posterior wall, and cardia of the stomach. 1 (3) It also affords the endoscopist a second chance after deploying the rubber band to review the pseudopolyp before resection. The rubber band can be removed and replaced if there is any doubt that it contains the entire lesion or if it seems to contain too much tissue with possible increased risk of complications. 13 (4) It uses a standard
484
NWAKAKWA & FLEISCHER
A
B Figure 1. EMR-band ligation technique. A , Spraying mucosa! surface helps identify and delineate the mucosa! abnormality. B, Lesion before and after submucosal injection.
ENDOSCOPIC MUCOSAL RESECTION OF THE ESOPHAGUS
485
c
D Figure 1 (Continued). C, Tissue is suctioned into cap and band applied. 0, Banded lesion before and after mucosectomy.
486
NWAKAKWA & FLEISCHER
Figure 2. Endoscopic view of lesion after banding (left) and after mucosectomy (right) .
endoscope, not the two-channel endoscope required in some of the other techniques. The disadvantages of this technique are that (1) it requires several intubations with and without the overtube, and (2) en bloc resected specimens are usually 12 mm or less. 1 The major complications of EMR band ligation are bleeding and perforation. 3 As mentioned previously there are no direct comparisons of the complication rates with other techniques in the literature. It seems likely that these complications are less related to the individual EMR technique than the nature, size, and location of the lesion that is being resected, and the experience of the endoscopist. The area in which EMR has been used effectively is in curative treatment of early cancers and premalignant lesions. It not only provides a less invasive treatment option than conventional surgery but also is able to provide en bloc tissue containing the entire lesion for histologic evaluation, the latter being its advantage over other less invasive options like photodynamic therapy, or thermal devices that ablate the lesion without providing histologic samples. It is more commonly used in Japan and other countries in the East where the incidence of gastric and esophageal cancer is high and elaborate screening programs are being carried out. It is becoming more common in the West, however, where it should find acceptance in treatment of early esophageal cancers or dysplastic esophageal lesions identified for example on patients with Barrett's esophagus who undergo screening.
Table 1. RATE OF COMPLETE RESECTION AND MAJOR COMPLICATIONS OF EMR- BAND LITIGATION Number of Patients
Number of Lesions
Akiyama
27
40
Suzuki
37
40
4 4 (dogs) 5 (patients) 4
4 19 5 4
Lee Fleischer Yokoyama
""
00 'I
Histology
9 early gastric cancer 31 gastric adenomas 23 adenomas 17 carcinomas All adenocarcinoma N/A Moderate dysplasia All were early gastric cancers
Mean Size of Specimens Resected
Rate of Complete Resection
Major Complications
14.2 x 13.6 mm
100%
None
12.8 x 11 mm
100% antrum 80% angle 61 .1% body 0% cardia 75% 100% 60% 75%
None
10-15 mm (range) 12- 15 mm (range) Not available Not available
None 1 perforation 5.3% 1 bleeding 20% Not available
488
NWAKAKWA & FLEISCHER
References 1. Akiyama M, Ota M, Nakajima H, et al: Endoscopic mucosa! resection of gastric neoplasms using a ligating device. Gastrointest Enclose 45:182-186, 1997 2. Canto MI: Vital staining and Barrett's esophagus. Gastrointest Enclose 49:S12-16, 1999 3. Fleischer DE, Wang G, Dawsey S, et al: Tissue band ligation followed by snare resection (band and snare): A new technique for tissue acquisition in the esophagus. Gastrointest Enclose 44:68-72, 1996 4. Giovannini M, Bernardini D, Moutardier V, et al: Endoscopic mucosa! resection (EMR): Results and prognostic factors in 21 patients. Endoscopy 31:698- 701, 1999 5. Inoue H, Tani M, Nagai K, et al: Treatment of esophageal and gastric tumors. Endoscopy 31:47-55, 1999 6. Izumi Y, Inoue H, Kawano T, et al: Endosonography during endoscopic mucosa! resection to enhance its safety: A new technique. Surg Enclose 13:358-360, 1999 7. Lambert R: Endoscopic mucosectomy: An alternative treatment for superficial esophageal cancer. Recent Results Cancer Res 155:183-192, 2000 8. Lee DK, Lee SW, Kwon SO, et al: Endoscopic mucosectomy using an esophageal variceal ligation device for minute gastric cancer. Endoscopy 28:386-389, 1996 9. Makuuchi H, Kise Y, Shimada H, et al: Endoscopic mucosa! resection for early gastric cancer. Semin Surg Oncol 17:108-116, 1999 10. Ninomiya Y, Yanagisawa A, Kato Y, et al: Unrecognizable intramucosal spread of diffusetype mucosa! gastric carcinomas of less than 20 mm in size. Endoscopy 32:604-608, 2000 11. Roukos DH: Current status and future perspectives in gastric cancer management. Cancer Treat Rev 26:243-255, 2000 12. Sadahiro S, Ishida H, Tokunaga N, et al: Experimental assessment of endoscopic mucosectomy with a cap-fitted panendoscope. Endoscopy 30:713-717, 1998 13. Shikuwa S, Matsunaga K, Osabe M, et al: Esophageal granular cell tumor treated by endoscopic mucosa! resection using a ligating device. Gastrointest Enclose 47:529-531, 1998 14. Souquet JC, Napoleon B, Pujol B, et al: Echoendoscopy prior to endoscopic tumor therapy: More safety? Endoscopy 25:475-478, 1993 15. Suzuki Y, Hiraishi H, Kanke K, et al: Treatment of gastric tumors by endoscopic mucosa! resection with a ligating device. Gastrointest Enclose 49:192-198, 1999 16. Tanabe S, Koizumi W, KokutouM, et al: Usefulness of endoscopic aspiration mucosectomy as compared with strip biopsy for the treatment of gastric mucosa! cancer. Gastrointest Enclose 50:819-822, 1999 17. Waxman I, Saitoh Y: Clinical outcome of endoscopic mucosa! resection for superficial GI lesions and the role of high-frequency US probe sonography in an American population. Gastrointest Enclose 52:322-327, 2000 18. Yamamoto H, Koiwai H, Yube T, et al: A successful single-step endoscopic resection of a 40 millimeter flat-elevated tumor in the rectum: Endoscopic mucosa! resection using sodium hyaluronate. Gastrointest Enclose 50:701-704, 1999 19. Yamamoto H, Yube T, Isoda N, et al: A novel method of endoscopic mucosa! resection using sodium hyaluronate. Gastrointest Enclose 50:251-256, 1999 20. Yokoyama T, Usui K, Tsujimoto M, et al: A new endoscopic resection technique for early gastric cancer, using an endoscopic ligating device designed to treat esophageal varices:preliminary report of four cases. Endoscopy 27:283, 1995
Address reprint requests to David Fleischer, MD, MACP Division of Gastroenterology Georgetown University Medical Center Rm2122 Washington, DC 20007 e-mail: [email protected]