Endoscopic submucosal dissection for large protruding colorectal neoplasms: it still is a challenging procedure!

Endoscopic submucosal dissection (ESD) was first performed for the purpose of achieving en bloc resection of superficial gastric lesions [1]. Despite being technically more challenging, the ESD procedure has been extended to colorectal lesions, and colorectal ESD is now widely performed [2] [3] [4]. Unlike piecemeal snare resection, en bloc resection achieved by ESD enables adequate orientation of the pathology specimen and reliable staging of submucosal invasion, so preventing unnecessary surgery for lesions at low risk of lymph node metastasis [4]. In addition, a very low recurrence rate can be achieved through complete en bloc resection [5].

In this issue of Endoscopy, Sakamoto et al. report on the retrospective outcomes of ESD for protruding colorectal neoplasms ≥ 20 mm in diameter [6]. They reviewed 112 consecutive patients and evaluated the transition in outcomes over 12 years. While most studies of colorectal ESD have focused on laterally spreading tumors, this study focused on large protruding lesions.

Fig. 1 Intense submucosal fibrosis of a large protruding tumor showing high grade dysplasia. Submucosal fibrosis frequently accompanies large protruding lesions. The fibrosis is believed to be caused by the mechanical force generated between the submucosa and the muscle layer as a result of intestinal peristalsis.

ESD for large protruding lesions is challenging, even for endoscopists expert in ESD, because of the intense submucosal fibrosis that frequently accompanies large protruding lesions([Fig. 1]). Sometimes, endoscopists cannot continue the submucosal dissection because of technical difficulty caused by this fibrosis, even though the lesions are benign. This situation results in a shift from the ESD procedure to piecemeal resection or surgery to remove the polyps. In the study by Sakamato et al., ESD procedures were stopped in 4.5 % of all patients owing to technical difficulties.

“… preoperative and intraoperative evaluation of resectability is essential; in the case of large protruding lesions, ESD procedures should be performed only by expert endoscopists who are highly experienced in colorectal ESD.”

Another challenging problem is the high incidence of massive submucosal invasion of large protruding lesions, which requires additional radical surgery even when the lesions can be removed successfully with the ESD technique. The pathological results reported by Sakamoto et al. also revealed a high incidence of massive submucosal invasion or deeper invasion (27.4 %).

A preoperative assessment of the technical difficulty and invasion depth is essential to determine the most appropriate treatment option. Endoscopic ultrasound (EUS) can be helpful, but is not always effective, especially in large protruding lesions; it is difficult to delineate the deep tissue structures because of the high rate of deep echo attenuation and the difficulty in vertical scanning of large protruding lesions [7]. Pit pattern analysis is also less accurate in large protruding lesions than in non-polypoid lesions [8]. Frequently, a decision on continuation of the ESD procedure can only be determined during the dissection. Severe fibrosis and muscle retraction are the key indicators to stop ESD and shift to surgical treatment.

Severe fibrosis is often associated with deep submucosal invasion and can lead to non-curative resection ([Fig. 2]) [9]. Additionally, it is the most powerful risk factor for complications and can interfere with en bloc resection. It is often accompanied by the development of submucosal vessels, which can make the ESD procedure more difficult. Therefore, an evaluation of the degree of submucosal fibrosis is required during the ESD [10].

Fig. 2 Severe fibrosis observed during endoscopic submucosal dissection of a sigmoid colon tumor showing massive submucosal invasion. The fibrosis is caused by desmoplastic reaction to cancer invasion and frequently leads to non-curative resection.

The “muscle-retracting sign” is the appearance of an underlying muscle layer being drawn up by the colorectal tumor to form a triangular shape that can be detected during ESD ([Fig. 3]) [11]. It is frequently found in large protruding lesions and is associated with deep submucosal invasion. In one study, the muscle-retracting sign was detected in 41.2 % of large sessile polyps (≥ 20 mm), and 75 % of the lesions that exhibited the muscle-retracting sign showed deep submucosal invasion [11].

Fig. 3 Muscle-retracting sign detected during endoscopic submucosal dissection of a large protruding tumor in the rectum. An underlying muscle layer is drawn up by the tumor to form a triangular shape. An uneven dissection line caused by the muscle-layer retraction makes a dissection difficult and increases the risk of adverse events.

Although it is difficult to remove tumors with accompanying submucosal fibrosis, removal can be accomplished successfully when the depth of the dissection line is appropriately maintained during the dissection procedure. The development of treatment devices, such as a traction device, or technological strategies, such as the pocket-creation method (PCM), can help to overcome submucosal fibrosis [12] [13]. The PCM is a novel technique to create a large submucosal pocket with a minimal mucosal incision to maintain a thick submucosal layer during the ESD procedure. A minimal incision prevents leakage of injected submucosal solution, and the tip of the endoscope in the submucosal pocket facilitates tissue traction; thereby enabling precise dissection just above the proper muscle [13] [14].

The removal of lesions exhibiting the muscle-retracting sign is more challenging because of an uneven dissection line caused by the muscle-layer retraction, which can increase the risk of adverse events. When the muscle-retracting sign is found, ESD is usually shifted to surgery in order to achieve complete removal and avoid the risk of adverse events. The muscle-retracting sign can result from desmoplastic reaction to cancer invasion or fibrosis caused by intestinal peristalsis [11]. For lower rectal lesions that show the muscle-retracting sign without cancer invasion, per-anal endoscopic myectomy (PAEM) can be considered as an alternative way of preserving the rectum while achieving complete removal of the tumor and a precise pathological diagnosis [15]. In the PAEM procedure, after making a circumferential dissection around the fibrotic area using a double-tunneling method, the inner circular muscle is cut in a circle and the space between the inner circular and outer longitudinal muscle is dissected [15]. PAEM is a very innovative technique to overcome the muscle-retracting sign, but high level endoscopic skill is needed.

The study of Sakamoto et al. divided the treatment period into six periods, and it evaluated the transition in outcomes over time. The second half of the study showed a statistically significant decreasing trend in the procedure time. Despite technological advances in treatment devices and strategies for the ESD procedure over 12 years, the results showed minimal progress in procedure time only, and no improvement in curability. This shows that performing ESD for large protruding lesions is still challenging. Therefore, preoperative and intraoperative evaluation of resectability is essential; in the case of large protruding lesions, ESD procedures should be performed only by expert endoscopists who are highly experienced in colorectal ESD.

A critical weakness of this retrospective study is the lack of factors associated with technical difficulty. In future prospective studies, it will be necessary to analyze the relationship between such factors and the clinical outcome. In addition, it would be helpful to know which new device or technique is most effective in treating severe fibrosis and the muscle-retracting sign.

• References

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