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A Large Endoscopic Resection by Endoscopic Submucosal Dissection Procedure for Early Gastric Cancer
CLINICAL GASTROENTEROLOGY AND HEPATOLOGY 2005;3:S71–S73
A Large Endoscopic Resection by Endoscopic Submucosal Dissection Procedure for Early Gastric Cancer TAKUJI GOTODA Endoscopy Division, National Cancer Center Hospital, Tokyo, Japan
Gastrectomy with lymph node dissection has provided an excellent therapeutic outcome for patients with early gastric cancer, with a 5-year survival rate of 96%. The prevalence of lymph node metastasis of intramucosaland submucosal-invading cancer was reported as approximately 3% and 20%, respectively, which means surgery may have been excessive for many patients with these diseases. The endoscopic distinction between mucosal and submucosal invasion is made correctly in only approximately 80% of tumors. However, this means that the pretreatment diagnosis is incorrect for 20% of those tumors otherwise identified as candidates for local treatment. Furthermore, the evaluation of lymphatic-vascular involvement associated with lymph node metastasis is available only through accurate histologic examination. It is essential to evaluate accurately the endoscopically resected specimen and then decide whether or not an additional surgical procedure is warranted. There are several techniques for endoscopic mucosal resection. It is difficult to correctly assess the depth of tumor invasion from resected materials by conventional endoscopic procedures in lesions larger than 15 mm. This is because such lesions often are resected piecemeal because of the size limitation of a resectable specimen. A new endoscopic procedure, endoscopic submucosal dissection, using an insulation-tipped needle knife specifically designed at the National Cancer Center Hospital, Japan, is superior to other endoscopic methods in the treatment of early gastric cancer, and provides an en bloc specimen. En bloc resections allow precise histologic staging and have the potential to prevent recurrent disease.
herapeutic endoscopy plays a major role in the management of gastric cancer. Its indications can be generalized into 3 broad categories: (1) to remove or obliterate, (2) to palliate obstruction, and (3) to treat bleeding. Endoscopic mucosal resection (EMR) currently is standard treatment for early gastric cancer in Japan. Outside Japan, it increasingly is gaining acceptance.1 The major advantage of EMR is its ability to provide pathologic staging without precluding future surgical therapy.2 Other endoscopic techniques also may cure
T
early gastric cancer by obliterating it, but they do not provide a pathologic specimen.
Rationale and Indication for Endoscopic Mucosal Resection Early gastric cancer is defined when tumor invasion is confined to the mucosa or submucosa (T1 cancer), irrespective of the presence of regional lymph node metastases.3 Because the presence of lymph node metastases has a significant adverse influence on patients’ prognosis, gastrectomy with lymph node dissection had been the standard treatment in the past in Japan even for patients who had early gastric cancer. The prevalence of lymph node metastases associated with intramucosal- and submucosal-invading gastric cancer was reported as approximately 3% and 20%, respectively. Because gastrectomy and lymph node resection was the treatment for all early gastric cancer, surgery may not be necessary for many patients with this disease.4 Considering the risks for gastrectomy and the negative effects on the patient’s quality of life, it is now possible to offer a local treatment for those patients with a very low risk for lymph node metastasis. By using our database involving more than 5000 patients who underwent gastrectomy with meticulous R2-level lymph node dissection, early gastric cancer with no lymph node metastasis was identified in varying depths of mucosal/submucosal involvement (Table 1).5 After EMR, the pathologic assessment of the depth of cancer invasion, the degree of differentiation of the cancer, and the involvement of lymphatics or vessels allow the risk for lymph node metastasis to be predicted based on the large database. The risk for developing lymph node metastasis or distant metastasis then is weighed against the risk for surgery. Abbreviations used in this paper: EMR, endoscopic mucosal resection; ESD, endoscopic submucosal dissection; IT, insulation-tipped. © 2005 by the American Gastroenterological Association 1542-3565/05/$30.00 PII: 10.1053/S1542-3565(05)00251-X
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TAKUJI GOTODA
CLINICAL GASTROENTEROLOGY AND HEPATOLOGY Vol. 3, No. 7
Table 1. Prevalence of Lymph Node Metastases in Early Gastric Cancer
Criteria Intramucosal cancer Differentiated (wells and/ or moderately differentiated and/or papillary adenocarcinoma) type No lymphatic-vessel invasion Irrespective of ulcer findings Tumor ⬍3 cm Intramucosal cancer Differentiated type No lymphatic-vessel invasion Without ulcer findings Irrespective of tumor size Intramucosal cancer Undifferentiated (poorly differentiated adenocarcinoma and/ or signet-ring cell carcinoma) type No lymphatic-vessel invasion Without ulcer findings Tumor ⬍3 cm Minute submucosal penetration (sm1) Differentiated type No lymphatic-vessel invasion Tumor ⬍3 cm
Incidence (no. with metastasis/ total number)
95% confidence interval
0/1230
0–.3
0/929
0–.4
0/256
0–1.3
0/145
0–2.5
Techniques and Complications of Endoscopic Submucosal Dissection The procedure begins by marking the periphery of the lesion using a standard needle knife with forced 20 W coagulation current (ICC200; ERBE, Tubringen, Germany). After injection of diluted epinephrine into the submucosal layer, a small initial incision is made with a standard needle knife with the 80W ENDO-CUT mode with effect 3 (ERBE) and the tip of the IT knife is inserted into the submucosal layer. Then circumferential
New Endoscopic Technique: Endoscopic Submucosal Dissection Although several techniques for EMR were reported, these techniques cannot be used to resect lesions larger than 15 mm en bloc.6 Piecemeal resections can lead to uncertainty of pathologic staging, and there is a high risk for recurrence after piecemeal resection. A new endoscopic technique using a modified needle knife, utilizing direct dissection of the submucosa, and classified as the endoscopic submucosal dissection (ESD) technique (Figure 1)7 was recently applied. We used an insulation-tipped diathermic knife (IT knife) that was developed at the National Cancer Center Hospital.8 Special endoscopic knives have been developed for en bloc resection with a standard single-channel gastroscope. This promising procedure has the advantage of achieving large en bloc resections, allows precise histologic staging, and may prevent disease recurrence.
Figure 1. (A) IT knife, (B) hook knife, (C) markings by needle knife with coagulation current, (D) circumferential mucosal cutting by IT knife with ENDO-CUT (ERBE) mode after diluted epinephrine injection to raise the submucosa, (E) dissecting submucosal layer using IT knife with ENDO-CUT (ERBE) after sufficient additional injection of diluted epinephrine injection to prevent perforation, (F) a large ESD defect after a complete 1-piece resection without perforation, (G) perforation by IT knife, and (H) complete closure by endoscopic clips.
July Supplement 2005
cutting of the periphery of the marking dots is performed using the IT knife with the 80W ENDO-CUT mode. The ceramic ball, an insulated product, fitted on the top of the IT knife, reduces the chance of perforation of the muscle layer. After additional submucosal injection, the submucosal layer under the lesion is dissected directly using the IT knife with a lateral movement. Complete endoscopic submucosal dissection can be performed to provide large, en bloc resection irrespective of the size of lesion. Finally, the resected specimen is retrieved using grasping forceps. The complications of EMR for early gastric cancer include pain, bleeding, and perforation. Bleeding is the most common complication, occurring in up to 8% of patients undergoing standard EMR and in up to 7% of patients undergoing ESD. Perforation is uncommon during EMR but is seen more commonly (4% of patients) during ESD. Both types of complications typically are treated successfully by endoscopy (Figure 1).
Future Directions Because the major advantage of EMR is its ability to provide pathologic staging among the therapeutic endoscopy techniques, early gastric cancer is being treated more frequently by EMR than by surgery in Japan. In the United States, EMR for Barrett’s esophagus with high-grade dysplasia now is becoming accepted increasingly and used regularly, however, obliteration therapy or a surgical approach are the main current. The indications, techniques, and pathologic assessment methods are demanding and require the endoscopists to survey the patients who underwent endoscopic treatment to ensure successful outcomes. Although endoscopic treatment including ESD should be safe, effective, and applicable to a variety of clinical situations, the ESD procedure has a higher incidence of complications than that with standard EMR procedures, and the ESD procedure requires an experienced endoscopist with a
ENDOSCOPIC SUBMUCOSAL DISSECTION PROCEDURE
S73
higher level of skill because the procedure has to be performed through only 1 gastroscope (1-handed surgery). A 2-handed procedure similar to an open surgery should be created in the near future for generalizing the ESD method.
Summary The recently developed endoscopic technique of ESD to dissect the submucosa directly allows resections of larger lesions en bloc for making more precise histologic staging and reducing local recurrences. Ideally, progress and simplification of the techniques have brought about great changes in the endoscopic field.
References 1. Soetikno R, Gotoda T, Nakanishi Y, et al. Endoscopic mucosal resection. Gastrointest Endosc 2003;57:567–579. 2. Ahmad NA, Kochman ML, Long WB, et al. Efficacy, safety, and clinical outcomes of endoscopic mucosal resection: a study of 101 cases. Gastrointest Endosc 2002;55:390 –396. 3. Japanese Gastric Cancer Association. Japanese classification of gastric carcinoma. Gastric Cancer 1998;1:10 –24. 4. Sano T, Kobori O, Muto T. Lymph node metastasis from early gastric cancer: endoscopic resection of tumour. Br J Surg 1992; 79:241–244. 5. Gotoda T, Yanagisawa A, Sasako M, et al. Incidence of lymph node metastasis from early gastric cancer: estimation with a large number of cases at two large centers. Gastric Cancer 2000; 3:219 –225. 6. Ell C, May A, Gossner L, et al. Endoscopic mucosectomy of early adenocarcinoma in patients with Barrett’s esophagus. Gastroenterology 1998;114:A589. 7. Ono H, Kondo H, Gotoda T, et al. Endoscopic mucosal resection for treatment of early gastric cancer. Gut 2001;48:225–229. 8. Gotoda T, Kondo H, Ono H, et al. A new endoscopic mucosal resection (EMR) procedure using an insulation-tipped diathermic (IT) knife for rectal flat lesions. Gastrointest Endosc 1999;50: 560 –563.
Address requests for reprints to: Takuji Gotoda, MD, Endoscopy Division, National Cancer Center Hospital, 5-1-1, Tsukiji, Chuo-Ku, Tokyo 104-0045, Japan. e-mail: [email protected]; fax: (81) 3-35423815.
A Large Endoscopic Resection by Endoscopic Submucosal Dissection Procedure for Early Gastric Cancer TAKUJI GOTODA Endoscopy Division, National Cancer Center Hospital, Tokyo, Japan
Gastrectomy with lymph node dissection has provided an excellent therapeutic outcome for patients with early gastric cancer, with a 5-year survival rate of 96%. The prevalence of lymph node metastasis of intramucosaland submucosal-invading cancer was reported as approximately 3% and 20%, respectively, which means surgery may have been excessive for many patients with these diseases. The endoscopic distinction between mucosal and submucosal invasion is made correctly in only approximately 80% of tumors. However, this means that the pretreatment diagnosis is incorrect for 20% of those tumors otherwise identified as candidates for local treatment. Furthermore, the evaluation of lymphatic-vascular involvement associated with lymph node metastasis is available only through accurate histologic examination. It is essential to evaluate accurately the endoscopically resected specimen and then decide whether or not an additional surgical procedure is warranted. There are several techniques for endoscopic mucosal resection. It is difficult to correctly assess the depth of tumor invasion from resected materials by conventional endoscopic procedures in lesions larger than 15 mm. This is because such lesions often are resected piecemeal because of the size limitation of a resectable specimen. A new endoscopic procedure, endoscopic submucosal dissection, using an insulation-tipped needle knife specifically designed at the National Cancer Center Hospital, Japan, is superior to other endoscopic methods in the treatment of early gastric cancer, and provides an en bloc specimen. En bloc resections allow precise histologic staging and have the potential to prevent recurrent disease.
herapeutic endoscopy plays a major role in the management of gastric cancer. Its indications can be generalized into 3 broad categories: (1) to remove or obliterate, (2) to palliate obstruction, and (3) to treat bleeding. Endoscopic mucosal resection (EMR) currently is standard treatment for early gastric cancer in Japan. Outside Japan, it increasingly is gaining acceptance.1 The major advantage of EMR is its ability to provide pathologic staging without precluding future surgical therapy.2 Other endoscopic techniques also may cure
T
early gastric cancer by obliterating it, but they do not provide a pathologic specimen.
Rationale and Indication for Endoscopic Mucosal Resection Early gastric cancer is defined when tumor invasion is confined to the mucosa or submucosa (T1 cancer), irrespective of the presence of regional lymph node metastases.3 Because the presence of lymph node metastases has a significant adverse influence on patients’ prognosis, gastrectomy with lymph node dissection had been the standard treatment in the past in Japan even for patients who had early gastric cancer. The prevalence of lymph node metastases associated with intramucosal- and submucosal-invading gastric cancer was reported as approximately 3% and 20%, respectively. Because gastrectomy and lymph node resection was the treatment for all early gastric cancer, surgery may not be necessary for many patients with this disease.4 Considering the risks for gastrectomy and the negative effects on the patient’s quality of life, it is now possible to offer a local treatment for those patients with a very low risk for lymph node metastasis. By using our database involving more than 5000 patients who underwent gastrectomy with meticulous R2-level lymph node dissection, early gastric cancer with no lymph node metastasis was identified in varying depths of mucosal/submucosal involvement (Table 1).5 After EMR, the pathologic assessment of the depth of cancer invasion, the degree of differentiation of the cancer, and the involvement of lymphatics or vessels allow the risk for lymph node metastasis to be predicted based on the large database. The risk for developing lymph node metastasis or distant metastasis then is weighed against the risk for surgery. Abbreviations used in this paper: EMR, endoscopic mucosal resection; ESD, endoscopic submucosal dissection; IT, insulation-tipped. © 2005 by the American Gastroenterological Association 1542-3565/05/$30.00 PII: 10.1053/S1542-3565(05)00251-X
S72
TAKUJI GOTODA
CLINICAL GASTROENTEROLOGY AND HEPATOLOGY Vol. 3, No. 7
Table 1. Prevalence of Lymph Node Metastases in Early Gastric Cancer
Criteria Intramucosal cancer Differentiated (wells and/ or moderately differentiated and/or papillary adenocarcinoma) type No lymphatic-vessel invasion Irrespective of ulcer findings Tumor ⬍3 cm Intramucosal cancer Differentiated type No lymphatic-vessel invasion Without ulcer findings Irrespective of tumor size Intramucosal cancer Undifferentiated (poorly differentiated adenocarcinoma and/ or signet-ring cell carcinoma) type No lymphatic-vessel invasion Without ulcer findings Tumor ⬍3 cm Minute submucosal penetration (sm1) Differentiated type No lymphatic-vessel invasion Tumor ⬍3 cm
Incidence (no. with metastasis/ total number)
95% confidence interval
0/1230
0–.3
0/929
0–.4
0/256
0–1.3
0/145
0–2.5
Techniques and Complications of Endoscopic Submucosal Dissection The procedure begins by marking the periphery of the lesion using a standard needle knife with forced 20 W coagulation current (ICC200; ERBE, Tubringen, Germany). After injection of diluted epinephrine into the submucosal layer, a small initial incision is made with a standard needle knife with the 80W ENDO-CUT mode with effect 3 (ERBE) and the tip of the IT knife is inserted into the submucosal layer. Then circumferential
New Endoscopic Technique: Endoscopic Submucosal Dissection Although several techniques for EMR were reported, these techniques cannot be used to resect lesions larger than 15 mm en bloc.6 Piecemeal resections can lead to uncertainty of pathologic staging, and there is a high risk for recurrence after piecemeal resection. A new endoscopic technique using a modified needle knife, utilizing direct dissection of the submucosa, and classified as the endoscopic submucosal dissection (ESD) technique (Figure 1)7 was recently applied. We used an insulation-tipped diathermic knife (IT knife) that was developed at the National Cancer Center Hospital.8 Special endoscopic knives have been developed for en bloc resection with a standard single-channel gastroscope. This promising procedure has the advantage of achieving large en bloc resections, allows precise histologic staging, and may prevent disease recurrence.
Figure 1. (A) IT knife, (B) hook knife, (C) markings by needle knife with coagulation current, (D) circumferential mucosal cutting by IT knife with ENDO-CUT (ERBE) mode after diluted epinephrine injection to raise the submucosa, (E) dissecting submucosal layer using IT knife with ENDO-CUT (ERBE) after sufficient additional injection of diluted epinephrine injection to prevent perforation, (F) a large ESD defect after a complete 1-piece resection without perforation, (G) perforation by IT knife, and (H) complete closure by endoscopic clips.
July Supplement 2005
cutting of the periphery of the marking dots is performed using the IT knife with the 80W ENDO-CUT mode. The ceramic ball, an insulated product, fitted on the top of the IT knife, reduces the chance of perforation of the muscle layer. After additional submucosal injection, the submucosal layer under the lesion is dissected directly using the IT knife with a lateral movement. Complete endoscopic submucosal dissection can be performed to provide large, en bloc resection irrespective of the size of lesion. Finally, the resected specimen is retrieved using grasping forceps. The complications of EMR for early gastric cancer include pain, bleeding, and perforation. Bleeding is the most common complication, occurring in up to 8% of patients undergoing standard EMR and in up to 7% of patients undergoing ESD. Perforation is uncommon during EMR but is seen more commonly (4% of patients) during ESD. Both types of complications typically are treated successfully by endoscopy (Figure 1).
Future Directions Because the major advantage of EMR is its ability to provide pathologic staging among the therapeutic endoscopy techniques, early gastric cancer is being treated more frequently by EMR than by surgery in Japan. In the United States, EMR for Barrett’s esophagus with high-grade dysplasia now is becoming accepted increasingly and used regularly, however, obliteration therapy or a surgical approach are the main current. The indications, techniques, and pathologic assessment methods are demanding and require the endoscopists to survey the patients who underwent endoscopic treatment to ensure successful outcomes. Although endoscopic treatment including ESD should be safe, effective, and applicable to a variety of clinical situations, the ESD procedure has a higher incidence of complications than that with standard EMR procedures, and the ESD procedure requires an experienced endoscopist with a
ENDOSCOPIC SUBMUCOSAL DISSECTION PROCEDURE
S73
higher level of skill because the procedure has to be performed through only 1 gastroscope (1-handed surgery). A 2-handed procedure similar to an open surgery should be created in the near future for generalizing the ESD method.
Summary The recently developed endoscopic technique of ESD to dissect the submucosa directly allows resections of larger lesions en bloc for making more precise histologic staging and reducing local recurrences. Ideally, progress and simplification of the techniques have brought about great changes in the endoscopic field.
References 1. Soetikno R, Gotoda T, Nakanishi Y, et al. Endoscopic mucosal resection. Gastrointest Endosc 2003;57:567–579. 2. Ahmad NA, Kochman ML, Long WB, et al. Efficacy, safety, and clinical outcomes of endoscopic mucosal resection: a study of 101 cases. Gastrointest Endosc 2002;55:390 –396. 3. Japanese Gastric Cancer Association. Japanese classification of gastric carcinoma. Gastric Cancer 1998;1:10 –24. 4. Sano T, Kobori O, Muto T. Lymph node metastasis from early gastric cancer: endoscopic resection of tumour. Br J Surg 1992; 79:241–244. 5. Gotoda T, Yanagisawa A, Sasako M, et al. Incidence of lymph node metastasis from early gastric cancer: estimation with a large number of cases at two large centers. Gastric Cancer 2000; 3:219 –225. 6. Ell C, May A, Gossner L, et al. Endoscopic mucosectomy of early adenocarcinoma in patients with Barrett’s esophagus. Gastroenterology 1998;114:A589. 7. Ono H, Kondo H, Gotoda T, et al. Endoscopic mucosal resection for treatment of early gastric cancer. Gut 2001;48:225–229. 8. Gotoda T, Kondo H, Ono H, et al. A new endoscopic mucosal resection (EMR) procedure using an insulation-tipped diathermic (IT) knife for rectal flat lesions. Gastrointest Endosc 1999;50: 560 –563.
Address requests for reprints to: Takuji Gotoda, MD, Endoscopy Division, National Cancer Center Hospital, 5-1-1, Tsukiji, Chuo-Ku, Tokyo 104-0045, Japan. e-mail: [email protected]; fax: (81) 3-35423815.