How to justify endoscopic submucosal dissection in the Western world

 

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In Japan, endoscopic treatment is considered the treatment of choice for early gastroesophageal neoplasia. In the 1970 s, the high incidence of gastric cancer in Japan led to the initiation of screening programs, initially with double contrast studies and later with endoscopic inspection. As a result, the number of gastric and esophageal cancers detected at an early stage increased dramatically, and the endoscopic treatment of these early lesions evolved as a logical consequence.

Initially early gastric and esophageal cancers were treated with endoscopic mucosal resection (EMR) techniques, of which the cap-based techniques are the most widely accepted [1]. These techniques suffer from the limitation that only lesions of a relatively small size can be resected in one piece (i. e., en bloc resection). Lesions larger than 15 – 20 mm generally require resection in multiple pieces (i. e., piecemeal resection) [1] [2] [3] [4]. After piecemeal resection, however, it is difficult to assess the radicality at the resection margins. The radicality at the vertical resection margin can usually be adequately assessed, but since it is generally impossible to reconstruct the lesion from the resected specimens, radicality at the lateral resection margins can be uncertain.

To avoid this problem, a new technique was developed that allows en bloc resection of larger lesions. This technique, known as endoscopic submucosal dissection (ESD), starts with the endoscopic circumcision of a lesion, followed by dissection starting at the lateral edges and working through the submucosal layer until the lesion is removed in one piece. Large cohort studies, again from Japan, suggest that ESD is associated with a significantly higher rate of radical en bloc resections, which reduces the rate of local recurrences during follow-up [1] [2] [3] [4]. These studies, all from expert centers, have shown remarkably few complications, although a perforation rate of 5 % – 7 % is generally reported [1] [2] [3] [4]. These perforations are usually small in size and are most often detected and managed during the endoscopic intervention without compromising its success. These procedures are, however, considered to be technically demanding, with average procedure times of several hours even in expert hands.

What is unique about ESD in Japan? The Japanese setting is ideal for learning and practicing ESD. The most frequently encountered early neoplastic lesions in Japan are in the distal stomach. This is the area where the muscularis propria is relatively thick and where endoscopic maneuvers are easier to perform than in the proximal stomach or esophagus [1]. There are also fewer blood vessels, and they are smaller, than at more proximal locations in the stomach. Furthermore, endoscopic treatment of early neoplasia is widely practiced in Japan, and most trained endoscopists are familiar with the different EMR techniques. Against this background, moving into the more technically demanding area of ESD is relatively easy. The ESD skills are superimposed upon the EMR skills and a stepwise approach can be followed, starting with ESD of the most frequently encountered lesions in the distal stomach, then moving to lesions in the proximal stomach, with esophageal and colonic lesions as the final step [1] [5]. The esophagus and colon are considered more difficult for ESD because maneuverability is limited and the muscle layer is much thinner [6]. The general rule in Japan is that a minimum of 50 ESDs should be performed in the distal stomach before moving to the more complicated lesions and difficult locations [1] [5].

In the West, the setting for learning and practicing ESD is completely different. First, EMR is not widely practiced: in few Western countries is endoscopic treatment of early gastrointestinal neoplasia considered the treatment of choice, and not many Western endoscopists have enough experience with EMR onto which to superimpose their ESD experience [7] [8]. Second, early gastric cancer is relatively rare in the West; most of our early cancers are discovered in patients with Barrett’s esophagus. This makes it difficult to gain enough ESD experience with gastric cases before moving into the more dangerous locations in the esophagus or colon. Most tertiary referral centers will see fewer than 10 suitable patients per year, making it very hard to accumulate the 50 cases required to become proficient according to Japanese standards.

The danger therefore exists that Western endoscopists will be tempted to practice ESD in the lesions they most frequently encounter: early Barrett’s cancers and colonic polyps. It is questionable whether ESD is justified for these indications. Early Barrett’s cancer generally develops against a background of a ”field defect”. Delineating the lesion is therefore difficult: after en bloc EMR of small lesions, only 20 % are found upon histological evaluation to have negative resection margins [9]. This is likely to be the case after ESD as well. In addition, the Barrett’s mucosa that is left behind after endoscopic resection of focal lesions is associated with a recurrence rate of up to 30 % within 3 years [10] [11]. To reduce this risk, additional treatment is therefore required for the remaining Barrett’s segment, and effective tools for this are now available. In expert hands, stepwise endoscopic resection of the whole Barrett’s esophagus using piecemeal EMR has been shown to be effective in reducing the number of recurrences during follow-up [12] [13] [14]. In addition, combining endoscopic resection with radiofrequency ablation (RFA) may be safer than widespread endoscopic resection, since RFA maintains the functional integrity of the esophagus and is easier to perform [15] [16] [17] [18]. The availability of effective tools for treating the residual Barrett’s mucosa after endoscopic resection of focal lesions makes the theoretical advantage of ESD (preventing local recurrences) less relevant, especially if one bears in mind that ESD of early Barrett’s cancers is one of the most complicated ESD procedures. The submucosa in Barrett’s esophagus is often fibrotic due to the chronic inflammation of the overlying epithelium, and ESD here is generally associated with much more bleeding than is encountered for squamous esophageal lesions. In addition, the angulation of the distal esophagus and movement due to respiration, heartbeat, and motility add to the complexity of the procedure. This means that for ESD of early Barrett’s cancer there may be less to gain and more to lose: ESD is unlikely to be more successful than currently available treatment modalities and requires a level of endoscopic expertise that is generally not available, placing the patient at risk of significant complications.

The same probably also holds for most colonic polyps that are removed with ESD in the West. Most of the flat polyps encountered in the West are of the granular type for which, even in Japan, piecemeal resection is considered the treatment of choice given the low chance that these lesions harbor malignancy. Flat polyps of the nongranular type harbor malignancy at a higher rate but are much less frequent. In these lesions ESD may indeed achieve en bloc resection, but again this indication is at the upper end of the risk spectrum because of the thin muscle layer of the colon [6] [19].

So were do we stand with ESD in the Western world? We have to accept that we are technically less proficient than our Japanese colleagues who superimposed ESD on decades of EMR experience and were able to learn ESD by a safe and stepwise approach. In the West, we lack this underlying experience and we do not have the case volume to use the same stepwise approach in expanding the indications for ESD. So should we forget about performing ESD in the Western world?

Clearly, the answer is ”no”. ESD is just another evolutionary step in endoscopic surgery. It provides and requires new skills, devices, and disposables that will take endoscopy to a higher level. This can only be done by developing good quality training programs and performing these procedures under prospective registration, preferably even under institutional review board approval. Recent developments in providing countertraction during ESD procedures either with magnets, springs, multitask devices, double-lumen endoscopes, or triangulation devices developed for NOTES (natural-orifice transluminal endoscopic surgery) will likely make ESD easier and within the reach of Western endoscopists in the near future [20] [21] [22] [23] [24]. Practicing a new endoscopic technique is exciting: the demonstrations of our Japanese colleagues during live courses are impressive, and it may be tempting for those who feel that they are skilled interventional endoscopists to enter this arena as well. This editorial serves as a word of caution that in the West we run the danger that most ESDs will be performed by endoscopists who are not proficient and/or in lesions that may be just as well treated, more safely and probably more effectively, by piecemeal resection. ESD should therefore be restricted to endoscopists who have a track record in EMR, who have had proper hands-on training in animal labs, and who restrict their first clinical cases to gastric and rectal lesions, not embarking upon esophageal and colonic ESD until they are considered proficient.

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J. J. G. H. M. BergmanMD 

Department of Gastroenterology and Hepatology
Academic Medical Center Amsterdam

Room C2-116
Meibergdreef 9
1105 AZ Amsterdam
The Netherlands

Fax: +31-20-6917033

Email: J.J.Bergman@amc.uva.nl