Intraluminal Endoscopic Surgery: The Scioto Returns

Abstract

In 1868, the sailing ship Scioto carried the first major Japanese immigrants to the United States (Hawaii) where they worked on sugar plantations under difficult conditions. Despite many ups and downs, the exchanges between East and West have brought great advances to each group. In the field of gastrointestinal imaging and advanced technology, one of the newest and most significant of these advances is the development of intraluminal endoscopic surgery, commonly referred to as endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD). In contrast to natural orifice transluminal endoscopic surgery (NOTES), which was discussed in an earlier review,1Wallace M.B. Take NOTES (Natural Orifice Transluminal Endoscopic Surgery).Gastroenterology. 2006; 131: 11-12Abstract Full Text Full Text PDF Scopus (14) Google Scholar EMR and ESD focus on resection of gastrointestinal neoplasia confined to mucosa and submucosal layers without traversing the full thickness of the wall. These procedures have opened a broad array of therapeutic options for patients who previously required surgical resection. The techniques, which have been developed and mastered in Japan over the past 20 years, are now rapidly being evaluated in European and North American centers. With potential decline in diagnostic endoscopy, procedures such as EMR, ESD, and NOTES will likely become an increasing part of gastroenterologists, (and likely surgeons), practice in the coming decade.EMR was first reported by Tada et al2Tada M. Shimada M. Murakami F. Development of strip-biopsy.Gastrointest Endosc. 1984; 26: 833-839Google Scholar in Japan in the 1980s and was later revised to its current form by Inoue et al.3Inoue 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: 58-62Abstract Full Text PDF PubMed Scopus (525) Google Scholar In this form, which uses a clear cap fitted to the end of an endoscope (cap or C-EMR), lesions are resected using a 3-stage process (Figure 1A–C): (1) identifications of the lesion with chromoendoscopy or more recently advanced imaging techniques, (2) separation of the lesion by submucosal injection of a fluid cushion, and (3) resection of the lesion by suction into a cap-fitted endoscope and subsequent snare resection using a special snare that is looped in the distal rim of the cap-fitted endoscopic tip. Various modifications of the technique have been developed that use more viscous fluids for the submucosal injection, thus providing more durable “lifting” of the tumor for careful resection, and use of rubber-band ligating devices to suction and band the tumor, followed by snare resection. Commercial kits are now available, making the procedure more convenient and standardized. The major advantage of EMR is the ability to resect flat or nearly flat lesions down to the muscularis propria. EMR technology is highly complementary with recent advances in imaging technology, which allows improved detection of the same flat lesions. The major disadvantages of EMR include the lack of widespread training in the Western countries and the limit of 1–2 cm that can be removed in a single en bloc resection.Figure 1(A) Submucosal injection of fluid to lift neoplastic lesion (dark color) from deeper muscularis propria. (B) Suction of the lesion and surrounding mucosa into a cap-fitted endoscope. (C) Resection with snare fitted into the distal rim of the cap. (D) Example of early esophageal squamous carcinoma endoscopic mucosal resection. (All with permission from Fujishiro et al.5Fujishiro M. Yahagi N. Kakushima N. Kodashima S. Muraki Y. Ono S. Yamamichi N. Tateishi A. Shimizu Y. Oka M. Ogura K. Kawabe T. Ichinose M. Omata M. Endoscopic submucosal dissection of esophageal squamous cell neoplasms.Clin Gastroenterol Hepatol. 2006; 4: 688-694Abstract Full Text Full Text PDF PubMed Scopus (306) Google Scholar)View Large Image Figure ViewerDownload Hi-res image Download (PPT)ESD is a natural evolution of EMR, which allows resection of much larger lesions en bloc. ESD was first developed by Dr Ono in Japan in 2001. Like EMR, ESD relies on mechanical dissection along the submucosal plane to completely excise lesions of almost any size. Various dissection tools have been developed which all share the property of being capable of lateral dissection and pulling the tissue away from the deeper muscularis layer (Figure 2A). All use diathermy coagulation and cutting current to both cut and cauterize blood vessels. Typically a neoplastic lesion is identified using chromoendoscopy or advanced endoscopic imaging methods, followed by injection of the submucosal fluid to separate the lesion from the muscularis. A circumferential cut is made just outside the borders of the neoplasia, followed by submucosal dissection from one side of the lesion to the other until it is completely excised (Figure 2). Virtually any superficial lesion within the gastrointestinal track can, in theory, be resected by ESD. The most amenable lesions are those in the stomach or rectum where the thicker wall reduces the risk of perforation. Indications have now expanded to include the esophagus, gastroesophageal junction, and even the proximal colon. The major limitations of ESD are the high degree of technical skill required for safe and effective resection, the long procedure time (in some cases up to 5–6 hours for subtotal gastric mucosal resection), and higher complication rates. Although both EMR and ESD have now become the standard of care for early gastric neoplasia in Japan, their safety and efficacy are only recently being evaluated in a few specialized centers in the West.Figure 2ESD for early gastric cancer. (A) Triangle tip endoscopic knife for ESD. (B) Views of early gastric cancer before and after ESD, including oriented histologic specimen. (Copyright holder unknown.)View Large Image Figure ViewerDownload Hi-res image Download (PPT)The indications and clinical effectiveness of EMR and ESD have been extensively documented in observational trials. A critical part of EMR and ESD therapy is to ensure that the likelihood of lymph node metastases is very low. The best data for EMR and ESD are in early gastric cancer from Japanese cohorts. Gotoda et al4Gotoda T. Endoscopic resection of early gastric cancer: the Japanese perspective.Curr Opin Gastroenterol. 2006; 22: 561-569Crossref PubMed Scopus (92) Google Scholar have identified several factors which accurately identify a cohort of low risk of nodal metastases including; tumor confined to mucosal or upper third of submucosa (T1m or sm1), well or moderately differentiated, and no lymphovascular invasion, all of which is best determined on the resection specimen. Endoscopic ultrasound is not sufficiently accurate to make these determinations. In more than 2500 patients who underwent complete surgical gastrectomy and lymph node dissection, with these low-risk features, none had nodal metastases.4Gotoda T. Endoscopic resection of early gastric cancer: the Japanese perspective.Curr Opin Gastroenterol. 2006; 22: 561-569Crossref PubMed Scopus (92) Google Scholar These early data may be somewhat biased because Japanese pathologic classification previously staged carcinoma in cases where Western pathologists would only classify intraepithelial neoplasia (dysplasia). More recently, Japanese and Western pathologists have used the uniform Vienna classification, which has eliminated this bias and confirmed that early gastric cancer meeting these criteria still has a very low prevalence of nodal metastases.4Gotoda T. Endoscopic resection of early gastric cancer: the Japanese perspective.Curr Opin Gastroenterol. 2006; 22: 561-569Crossref PubMed Scopus (92) Google Scholar The strict guidelines for EMR, including lateral size of neoplasia <2 cm, and well-differentiated tumor, have resulted in 5-year cancer-specific rates of early gastric cancer of 99% for mucosal and 96% for submucosal tumors.4Gotoda T. Endoscopic resection of early gastric cancer: the Japanese perspective.Curr Opin Gastroenterol. 2006; 22: 561-569Crossref PubMed Scopus (92) Google Scholar Long-term cure rates for ESD for larger lesions are still being evaluated.Following the early Japanese success, indications for EMR and ESD have rapidly expanded to include early cancers of the squamous esophagus,5Fujishiro M. Yahagi N. Kakushima N. Kodashima S. Muraki Y. Ono S. Yamamichi N. Tateishi A. Shimizu Y. Oka M. Ogura K. Kawabe T. Ichinose M. Omata M. Endoscopic submucosal dissection of esophageal squamous cell neoplasms.Clin Gastroenterol Hepatol. 2006; 4: 688-694Abstract Full Text Full Text PDF PubMed Scopus (306) Google Scholar rectum,5Fujishiro M. Yahagi N. Kakushima N. Kodashima S. Muraki Y. Ono S. Yamamichi N. Tateishi A. Shimizu Y. Oka M. Ogura K. Kawabe T. Ichinose M. Omata M. Endoscopic submucosal dissection of esophageal squamous cell neoplasms.Clin Gastroenterol Hepatol. 2006; 4: 688-694Abstract Full Text Full Text PDF PubMed Scopus (306) Google Scholar proximal colon,6Hurlstone D.P. Sanders D.S. Thomson M. Cross S.S. “Salvage” endoscopic mucosal resection in the colon using a retroflexion gastroscope dissection technique: a prospective analysis.Endoscopy. 2006; 38: 902-906Crossref PubMed Scopus (20) Google Scholar gastroesophageal junction,7Kakushima N. Yahagi N. Fujishiro M. Kodashima S. Nakamura M. Omata M. Efficacy and safety of endoscopic submucosal dissection for tumors of the esophagogastric junction.Endoscopy. 2006; 38: 170-174Crossref PubMed Scopus (115) Google Scholar and Barrett esophagus.8Ell 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: 3-10Abstract Full Text Full Text PDF PubMed Scopus (463) Google Scholar Notably, the study by Ell et al8Ell 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: 3-10Abstract Full Text Full Text PDF PubMed Scopus (463) Google Scholar included 100 patients with confirmed T1 adenocarcinoma treated with EMR. Eleven percent of lesions had local recurrence that was successfully treated by repeat EMR for a 5-year cure rate of 98%.Despite these successes, there are major technology limitations of EMR and ESD as it is currently performed. The endoscope and cutting tools are limited to a single axis (as if performing surgery with one hand) that does not allow traction or countertraction to easily separate tumors from healthy tissue. New innovative technology, particularly in the field of NOTES, is progressing rapidly with dual-headed operating endoscopes, magnetic grasping devices that can be delivered into the gastrointestinal tract and controlled via external skin magnets, and multiple bending angle endoscopies. Training is also a major issue in the West. Currently >90% of published series on EMR and ESD are from Japan. German and British investigators have just recently begun to publish large prospective series, but there is no long-term, large series from the United States. The current competitive trends for diagnostic and screening examination of the colon will likely push the field of gastroenterology toward more therapeutic procedures, including EMR. The surgical community is also rapidly investigating endoscopic resection techniques such as transanal endoscopic microsurgery (TEMS). These converging trends of advanced endoscopic surgical technology, demand for less invasive procedures, and noninvasive diagnostic imaging will likely result in a new breed of endoscopic gastrointestinal surgeon with advanced training in surgical and endoscopic techniques. This has already occurred in Japan where physicians, receiving both classic surgery and gastroenterology/endoscopy training, are leading the effort. The return of the Scioto is, indeed, welcome. In 1868, the sailing ship Scioto carried the first major Japanese immigrants to the United States (Hawaii) where they worked on sugar plantations under difficult conditions. Despite many ups and downs, the exchanges between East and West have brought great advances to each group. In the field of gastrointestinal imaging and advanced technology, one of the newest and most significant of these advances is the development of intraluminal endoscopic surgery, commonly referred to as endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD). In contrast to natural orifice transluminal endoscopic surgery (NOTES), which was discussed in an earlier review,1Wallace M.B. Take NOTES (Natural Orifice Transluminal Endoscopic Surgery).Gastroenterology. 2006; 131: 11-12Abstract Full Text Full Text PDF Scopus (14) Google Scholar EMR and ESD focus on resection of gastrointestinal neoplasia confined to mucosa and submucosal layers without traversing the full thickness of the wall. These procedures have opened a broad array of therapeutic options for patients who previously required surgical resection. The techniques, which have been developed and mastered in Japan over the past 20 years, are now rapidly being evaluated in European and North American centers. With potential decline in diagnostic endoscopy, procedures such as EMR, ESD, and NOTES will likely become an increasing part of gastroenterologists, (and likely surgeons), practice in the coming decade. EMR was first reported by Tada et al2Tada M. Shimada M. Murakami F. Development of strip-biopsy.Gastrointest Endosc. 1984; 26: 833-839Google Scholar in Japan in the 1980s and was later revised to its current form by Inoue et al.3Inoue 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: 58-62Abstract Full Text PDF PubMed Scopus (525) Google Scholar In this form, which uses a clear cap fitted to the end of an endoscope (cap or C-EMR), lesions are resected using a 3-stage process (Figure 1A–C): (1) identifications of the lesion with chromoendoscopy or more recently advanced imaging techniques, (2) separation of the lesion by submucosal injection of a fluid cushion, and (3) resection of the lesion by suction into a cap-fitted endoscope and subsequent snare resection using a special snare that is looped in the distal rim of the cap-fitted endoscopic tip. Various modifications of the technique have been developed that use more viscous fluids for the submucosal injection, thus providing more durable “lifting” of the tumor for careful resection, and use of rubber-band ligating devices to suction and band the tumor, followed by snare resection. Commercial kits are now available, making the procedure more convenient and standardized. The major advantage of EMR is the ability to resect flat or nearly flat lesions down to the muscularis propria. EMR technology is highly complementary with recent advances in imaging technology, which allows improved detection of the same flat lesions. The major disadvantages of EMR include the lack of widespread training in the Western countries and the limit of 1–2 cm that can be removed in a single en bloc resection. ESD is a natural evolution of EMR, which allows resection of much larger lesions en bloc. ESD was first developed by Dr Ono in Japan in 2001. Like EMR, ESD relies on mechanical dissection along the submucosal plane to completely excise lesions of almost any size. Various dissection tools have been developed which all share the property of being capable of lateral dissection and pulling the tissue away from the deeper muscularis layer (Figure 2A). All use diathermy coagulation and cutting current to both cut and cauterize blood vessels. Typically a neoplastic lesion is identified using chromoendoscopy or advanced endoscopic imaging methods, followed by injection of the submucosal fluid to separate the lesion from the muscularis. A circumferential cut is made just outside the borders of the neoplasia, followed by submucosal dissection from one side of the lesion to the other until it is completely excised (Figure 2). Virtually any superficial lesion within the gastrointestinal track can, in theory, be resected by ESD. The most amenable lesions are those in the stomach or rectum where the thicker wall reduces the risk of perforation. Indications have now expanded to include the esophagus, gastroesophageal junction, and even the proximal colon. The major limitations of ESD are the high degree of technical skill required for safe and effective resection, the long procedure time (in some cases up to 5–6 hours for subtotal gastric mucosal resection), and higher complication rates. Although both EMR and ESD have now become the standard of care for early gastric neoplasia in Japan, their safety and efficacy are only recently being evaluated in a few specialized centers in the West. The indications and clinical effectiveness of EMR and ESD have been extensively documented in observational trials. A critical part of EMR and ESD therapy is to ensure that the likelihood of lymph node metastases is very low. The best data for EMR and ESD are in early gastric cancer from Japanese cohorts. Gotoda et al4Gotoda T. Endoscopic resection of early gastric cancer: the Japanese perspective.Curr Opin Gastroenterol. 2006; 22: 561-569Crossref PubMed Scopus (92) Google Scholar have identified several factors which accurately identify a cohort of low risk of nodal metastases including; tumor confined to mucosal or upper third of submucosa (T1m or sm1), well or moderately differentiated, and no lymphovascular invasion, all of which is best determined on the resection specimen. Endoscopic ultrasound is not sufficiently accurate to make these determinations. In more than 2500 patients who underwent complete surgical gastrectomy and lymph node dissection, with these low-risk features, none had nodal metastases.4Gotoda T. Endoscopic resection of early gastric cancer: the Japanese perspective.Curr Opin Gastroenterol. 2006; 22: 561-569Crossref PubMed Scopus (92) Google Scholar These early data may be somewhat biased because Japanese pathologic classification previously staged carcinoma in cases where Western pathologists would only classify intraepithelial neoplasia (dysplasia). More recently, Japanese and Western pathologists have used the uniform Vienna classification, which has eliminated this bias and confirmed that early gastric cancer meeting these criteria still has a very low prevalence of nodal metastases.4Gotoda T. Endoscopic resection of early gastric cancer: the Japanese perspective.Curr Opin Gastroenterol. 2006; 22: 561-569Crossref PubMed Scopus (92) Google Scholar The strict guidelines for EMR, including lateral size of neoplasia <2 cm, and well-differentiated tumor, have resulted in 5-year cancer-specific rates of early gastric cancer of 99% for mucosal and 96% for submucosal tumors.4Gotoda T. Endoscopic resection of early gastric cancer: the Japanese perspective.Curr Opin Gastroenterol. 2006; 22: 561-569Crossref PubMed Scopus (92) Google Scholar Long-term cure rates for ESD for larger lesions are still being evaluated. Following the early Japanese success, indications for EMR and ESD have rapidly expanded to include early cancers of the squamous esophagus,5Fujishiro M. Yahagi N. Kakushima N. Kodashima S. Muraki Y. Ono S. Yamamichi N. Tateishi A. Shimizu Y. Oka M. Ogura K. Kawabe T. Ichinose M. Omata M. Endoscopic submucosal dissection of esophageal squamous cell neoplasms.Clin Gastroenterol Hepatol. 2006; 4: 688-694Abstract Full Text Full Text PDF PubMed Scopus (306) Google Scholar rectum,5Fujishiro M. Yahagi N. Kakushima N. Kodashima S. Muraki Y. Ono S. Yamamichi N. Tateishi A. Shimizu Y. Oka M. Ogura K. Kawabe T. Ichinose M. Omata M. Endoscopic submucosal dissection of esophageal squamous cell neoplasms.Clin Gastroenterol Hepatol. 2006; 4: 688-694Abstract Full Text Full Text PDF PubMed Scopus (306) Google Scholar proximal colon,6Hurlstone D.P. Sanders D.S. Thomson M. Cross S.S. “Salvage” endoscopic mucosal resection in the colon using a retroflexion gastroscope dissection technique: a prospective analysis.Endoscopy. 2006; 38: 902-906Crossref PubMed Scopus (20) Google Scholar gastroesophageal junction,7Kakushima N. Yahagi N. Fujishiro M. Kodashima S. Nakamura M. Omata M. Efficacy and safety of endoscopic submucosal dissection for tumors of the esophagogastric junction.Endoscopy. 2006; 38: 170-174Crossref PubMed Scopus (115) Google Scholar and Barrett esophagus.8Ell 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: 3-10Abstract Full Text Full Text PDF PubMed Scopus (463) Google Scholar Notably, the study by Ell et al8Ell 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: 3-10Abstract Full Text Full Text PDF PubMed Scopus (463) Google Scholar included 100 patients with confirmed T1 adenocarcinoma treated with EMR. Eleven percent of lesions had local recurrence that was successfully treated by repeat EMR for a 5-year cure rate of 98%. Despite these successes, there are major technology limitations of EMR and ESD as it is currently performed. The endoscope and cutting tools are limited to a single axis (as if performing surgery with one hand) that does not allow traction or countertraction to easily separate tumors from healthy tissue. New innovative technology, particularly in the field of NOTES, is progressing rapidly with dual-headed operating endoscopes, magnetic grasping devices that can be delivered into the gastrointestinal tract and controlled via external skin magnets, and multiple bending angle endoscopies. Training is also a major issue in the West. Currently >90% of published series on EMR and ESD are from Japan. German and British investigators have just recently begun to publish large prospective series, but there is no long-term, large series from the United States. The current competitive trends for diagnostic and screening examination of the colon will likely push the field of gastroenterology toward more therapeutic procedures, including EMR. The surgical community is also rapidly investigating endoscopic resection techniques such as transanal endoscopic microsurgery (TEMS). These converging trends of advanced endoscopic surgical technology, demand for less invasive procedures, and noninvasive diagnostic imaging will likely result in a new breed of endoscopic gastrointestinal surgeon with advanced training in surgical and endoscopic techniques. This has already occurred in Japan where physicians, receiving both classic surgery and gastroenterology/endoscopy training, are leading the effort. The return of the Scioto is, indeed, welcome.