Endoscopic submucosal dissection - cure in one piece

With the widespread availability of flexible endoscopes and incorporation of endoscopic screening and surveillance procedures in gastroenterology, a substantial proportion of gastrointestinal cancers are being diagnosed at an early stage. Available data from the Surveillance, Epidemiology, and End Results program of the United States National Cancer Institute, suggest that more than 15 % of all esophageal, gastric, and colorectal cancers are early gastrointestinal cancers, and potential candidates for curative endoscopic resection. The technique of endoscopic mucosal resection (EMR) initially described in the early 1980s has been gradually accepted for management of superficial gastrointestinal neoplastic lesions. Cumulative experience from large pathological databases suggests that superficial gastrointestinal cancers with favorable histological and morphological attributes have very low risk of lymph nodal metastasis [1] [2] [3]. The original idea that a carefully done EMR, achieving tumor-free lateral and deep margins, should be curative has been borne out by observational longitudinal studies from different centers reporting excellent long-term outcomes in terms of recurrence-free cure rates and overall survival [4] [5] [6] [7]. Different techniques of EMR have been perfected by experts in different centers, mostly in Japan, and over the last decade this procedure has slowly gained acceptance in the western world.

Although EMR is an attractive therapeutic option for selected patients with early cancers, the size of the lesion remains a critical limitation. Any lesion more than 20 mm in size is difficult to remove en bloc, and frequently such lesions are removed in a piecemeal fashion. Even with lesions that are less than 20 mm in size, the en bloc resection rate is only about 75 % [4]. With piecemeal resection it is difficult to be sure that the entire lesion has been completely resected and, even with close scrutiny, often it is impossible to know whether the resected lateral and deep margins are free of neoplastic tissue. Studies have shown that with piecemeal resection, local recurrence rates are higher compared with the rate achieved with en bloc resection [8] [9].

As the techniques of EMR were being perfected, and improvements associated with procedural safety emerged, the concept of endoscopic submucosal dissection (ESD) gradually evolved almost simultaneously in many centers in Japan. The technique of ESD differs from EMR in one basic aspect. During EMR, the neoplastic tissue is resected rapidly, and the endoscopist has little or no control in adjusting the plane or the margin of resection; during ESD, the endoscopist deliberately and diligently creates a plane of dissection through the submucosa while attempting to achieve a margin that should be free of neoplastic tissue. In this issue of Endoscopy, several groups of investigators from Asia report their experience in ESD. Onozato et al. describe their experience with ESD in 160 patients with early gastric cancer [10]. The reported complete resection rate was more than 90 % even for ulcerated lesions. Complication rates were higher with larger lesions but, remarkably, all complications including perforations could be managed conservatively without surgical intervention. One of the greatest concerns with ESD is the perceived need for emergent surgical intervention in case of complications such as free perforation. However, as more experience is accumulated with ESD in different centers, it is increasingly becoming apparent that a large proportion of such perforations can be managed by endoscopic closure of the site of perforation along with conservative measures, and surgical interventions can be avoided in most cases. As emphasized by Fujishiro et al., such a conservative approach is most likely to be successful in those patients with a small perforation in the upper gastrointestinal tract with minimal peritoneal contamination and in whom complete endoscopic closure is accomplished [11].

As we learn more about ESD from different centers, it is clear that ESD is in an early stage of development with several unexplored issues. The indications for ESD have not been clearly established yet and, as we have seen with EMR, it is likely that as more experience is gained with ESD, the clinical indications will be better defined. In this issue of Endoscopy, Oka et al. report that ESD is a safe and effective procedure for managing residual or locally recurrent early gastric cancer after EMR [12]. An important question that remains to be answered is whether ESD should be performed in situations where EMR seems to be adequate - does it give any added benefit in terms of rates of local recurrence and overall survival? Few reports of ESD for resection of submucosal lesions have been published. In an accompanying paper, Lee et al. from Taiwan report successful resection of neoplastic lesions arising from the muscularis propria [13]. Although it appears feasible to resect such deeper lesions by ESD, currently there are not enough data in terms of rates of complications and long-term recurrence in this setting. Several different techniques of ESD have been described, using different endoscopic electrocautery accessories and also differing with respect to the types of submucosal solutions used; controlled data will be needed to substantiate any claim of superiority of one technique over another. It may be too simplistic to expect that one particular technique will be universally applicable in all scenarios; it is more likely that endoscopists performing ESD will need to be familiar with a number of different accessories for performing ESD of varying degrees of difficulty in different sites of the gastrointestinal tract. It appears to be considerably more difficult to carry out ESD for removal of esophageal and colonic lesions compared with ESD for gastric lesions. Even with gastric lesions it is found that proximal lesions, larger lesions, and those with ulceration have higher rates of incomplete resection and complications, despite requiring longer procedure times [14]; it is likely that the presence of these features acts synergistically to add to the degree of difficulty in performing ESD.

Recent years have seen the continual emergence of newer techniques and endoscopic instruments related to endoscopic surgery. In this issue of Endoscopy, two groups of investigators describe the use of a lockable external grasping forceps inserted alongside the endoscope [15] and a prototype double-channel endoscope fitted with a multiply flexible section [16] to facilitate countertraction during dissection. Other methods of countertraction, which is important for maintaining the correct plane of dissection, have been reported, such as traction through a sinker-device, magnetic traction and even percutaneous traction through a laparoscopic port. It is certain that the technique of ESD will evolve rapidly in the near future in the pursuit of perfection. What are the likely future developments in ESD technology? Development of improved endoscopic devices, particularly multitasking, variably flexible and steerable endoscopic platforms, for improved access, inspection, tissue traction, approximation, and triangulation, will have a radical impact on future endoscopic surgery. Substantial progress has already been made in the areas of robotic-assisted surgery and the development of endoscopic suturing devices. The other area of technological breakthrough will likely be in the area of endoscopic imaging for improved definition and accurate prediction of depth of invasion in a neoplastic lesion. Also, the development of auxiliary imaging devices, such as maneuverable wireless capsule imagers providing multiple simultaneous endoscopic images with spatial orientation, will surely facilitate endoscopic resection. One of the limitations of any endoscopic resection procedure for early gastrointestinal cancer is our inability to conclusively exclude the presence of lymph nodal involvement, which essentially nullifies the benefits of ESD. In the near future, combined multidisciplinary techniques such natural orifice transluminal endoscopic surgery (NOTES) will likely be available to assess and manage lymph nodal involvement; this will certainly broaden the scope of ESD.

Whenever an endoscopist practicing in the Western world reads and hears about ESD, a dual response is likely to be evoked - on the one hand of admiration and on the other of skepticism. Will ESD be ever widely accepted in the West? Could we perform ESD and also, should we perform ESD? In the West, acceptance of EMR has been slow at best. In the Western countries, indications for endoscopic resection are somewhat different from those in Japan, where a large majority of these procedures are done in patients with early gastric cancer. In Europe and in the United States, one of the main indications for endoscopic resection will be early esophageal cancer in a setting of Barrett’s esophagus. It is well known that because of the rich mucosal and submucosal lymphatic network in the esophagus, the risk of lymph nodal involvement is higher and endoscopic resection for any lesion beyond deeper mucosa may not even be indicated. The other important indication will be for removal of large colorectal polyps not amenable to standard endoscopic polypectomy. However with advancement in the techniques of laparoscopic colectomy, the superiority of ESD over minimally invasive surgery will have to be demonstrated with conviction, in terms of outcomes including patient preference. With the ever-increasing cost of healthcare, the cost-effectiveness of any medical intervention will be a critical factor in its acceptance. For most abdominal surgical procedures, postoperative length of hospital stay is a major component of the overall cost. Most of the patients undergoing ESD in Japan are currently observed for more than a week as inpatients. Unless ESD develops into an ambulatory surgical procedure or at the least patients undergoing ESD have a shorter length of stay, it is unlikely that, ESD will be considered to be a cost-saving procedure, in the United States at least. It is likely that in the west, ESD if adopted will remain confined to tertiary level academic centers and to therapeutic endoscopists in the foreseeable future. Even in these institutions, ensuring adequate volumes of ESD procedures for initial training and maintenance of endoscopic skills will be a major hurdle. It is obvious that a technically demanding endoscopic procedure like ESD will have a steep learning curve. All experts performing ESD emphasize the importance of extensive training; however, no training curriculum has yet been formally proposed by any professional society.

John W. Kirklin, a famous American surgeon once said, “Surgery is always second best. If you can do something else, it’s better.” There is no doubt that ESD is a major advancement in therapeutic endoscopy and eventually may become the method of choice for curative treatment of early gastrointestinal cancer. The initial skepticism is healthy and should be welcomed. It is to be hoped that extraordinary technological development in the future will enable complex endoscopic procedures such as ESD to disseminate from the high temples of master endoscopists into common endoscopic practice.

Competing interests: None

References

• 1 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
• 2 Stein H J, Feith M, Bruecher B L. et al . Early esophageal cancer: pattern of lymphatic spread and prognostic factors for long-term survival after surgical resection.  Ann Surg. 2005;  242 566-573
• 3 Kitajima K, Fujimori T, Fujii S. et al . Correlations between lymph node metastasis and depth of submucosal invasion in submucosal invasive colorectal carcinoma: a Japanese collaborative study.  J Gastroenterol. 2004;  39 534-543
• 4 Kojima T, Parra-Blanco A, Takahashi H, Fujita R. Outcome of endoscopic mucosal resection for early gastric cancer: review of the Japanese literature.  Gastrointest Endosc. 1998;  48 550-554
• 5 Kudo S. Endoscopic mucosal resection of flat and depressed types of early colorectal cancer.  Endoscopy. 1993;  25 455-461
• 6 Makuuchi H. Endoscopic mucosal resection for mucosal cancer in the esophagus.  Gastrointest Endosc Clin N Am. 2001;  11 445-458
• 7 Pech O, May A, Gossner L. et al . Long term follow up of endoscopic resection in patients with early squamous cell carcinoma of the esophagus - a prospective study.  Gastrointest Endosc. 2006;  63 AB122
• 8 Ono H, Kondo H, Gotoda T. et al . Endoscopic mucosal resection for treatment of early gastric cancer.  Gut. 2001;  48 225-229
• 9 Miyamoto S, Muto M, Hamamoto Y. et al . New technique for endoscopic mucosal resection with an insulated-tip electrosurgical knife improves the completeness of resection of intramucosal gastric neoplasms.  Gastrointest Endosc. 2002;  55 576-581
• 10 Onozato Y, Ishihara H, Iizuka H. et al . Endoscopic submucosal dissection (ESD) for early gastric cancers and large flat adenomas.  Endoscopy. 2006;  10 980-987
• 11 Fujishiro M, Yahagi N, Kakushima N. et al . Successful non-surgical managements after perforation caused by endoscopic submucosal dissection for the gastrointestinal epithelial neoplasia.  Endoscopy. 2006;  10 1001-1007
• 12 Oka S, Tanaka S, Kaneko I. et al . Endoscopic submucosal dissection for residue/local recurrence of early gastric cancer after endoscopic mucosal resection.  Endoscopy. 2006;  10 996-1000
• 13 Lee I, Lin P Y, Tung S. et al . Endoscopic submucosal dissection for the treatment of intraluminal gastric subepithelial tumors originating from muscularis propria.  Endoscopy. 2006;  10 1024-1028
• 14 Imagawa A, Okada H, Kawahara Y. et al . Endoscopic submucosal dissection (ESD) for early gastric cancer: results and degrees of technical difficulty as well as success.  Endoscopy. 2006;  10 987-990
• 15 Imaeda H, Iwao H, Ogata H. et al . A new technique for endoscopic submucosal dissection for early gastric cancer using an external grasping forceps.  Endoscopy. 2006;  10 1007-1010
• 16 Yonezawa J, Kaise M, Sumiyama K. et al . A novel therapeutic endoscope with lesion-countertraction and knife-swinging functions facilitates en bloc endoscopic submucosal dissection.  Endoscopy. 2006;  10 1011-1015