CURRENT STATUS AND FUTURE PERSPECTIVES OF ENDOSCOPIC SUBMUCOSAL DISSECTION FOR COLORECTAL TUMORS

Authors


Shinji Tanaka, Department of Endoscopy, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan. Email: colon@hiroshima-u.ac.jp

Abstract

Endoscopic submucosal dissection (ESD) allows for en bloc tumor resection irrespective of the size of the lesion. In Japan, ESD has been established as a standard method for endoscopic ablation of malignant tumors in the upper gastrointestinal tract. Although the use of colorectal ESD has been gradually spreading with the development of numerous devices, ESD has not yet been fully established as a standard therapeutic method for colorectal lesions. Currently, colorectal ESD is performed as an ‘advanced medical treatment’ without national health insurance coverage. With the recent accumulation of numerous cases, the safety and simplicity of colorectal ESD have improved remarkably. Currently in Japan, a prospective multicenter cohort study organized by the Japan Gastroenterological Endoscopy Society is ongoing to clarify the safety and efficacy of colorectal ESD to obtain remuneration from national health insurance. In this report, we showed the outcome regarding safety and efficacy of colorectal ESD through a review of the published work. Of 2719 cases with colorectal ESD at 13 institutions, the complete en bloc resection and perforation rates were 82.8% (61–98.2%, 2082/2516) and 4.7% (1.4–8.2%, 127/2719), respectively. Additional surgery for perforation was very rare because perforations were tiny enough to be closed endoscopically by clips in most of the cases and treated conservatively. In the near future, colorectal ESD will be a common therapeutic method for early colorectal carcinoma.

INTRODUCTION

Endoscopic submucosal dissection (ESD) enables en bloc resection of a lesion irrespective of its size.1,2 Accurate histopathological diagnosis can be attained using ESD, and the affected organ can be preserved after the treatment. Therefore, ESD is widely used for the treatment of carcinoma of the upper gastrointestinal tract, particularly in the stomach,3,4 and in Japan, national health insurance covers the expense of ESD as a therapeutic procedure for early gastric and esophageal carcinoma. ESD has also been increasingly applied to the colon and rectum (Fig. 1). Although ESD has not yet been recognized as a conventional therapeutic procedure for early colorectal carcinoma due to its technical difficulty, it has been made easier and safer by recent advances both in equipment (Figs 2,3) and technique, as well as the experience of many cases.5 In addition, the use of a carbon dioxide (CO2) insufflation system has made it easier to perform colorectal ESD.2,6 CO2 can be absorbed by tissue at a speed more than 100 times that of room air. The use of this system can decrease colonic distension during ESD due to air insufflation. In addition, even when perforation occurs and the hole is closed with a clip, the risk of peritonitis is remarkably decreased.6 In this chapter, we will describe the indications for colorectal ESD and the outcomes regarding safety and efficacy from a review of the published work. Additionally, we will discuss the future perspective of colorectal ESD.

Figure 1.

(a) Standard endoscopic submucosal dissection (ESD) case for granular-type laterally spreading tumors, nodular mixed type, Rectsigmoid, 90 mm in diameter. Left, standard colonoscopic view; right, indigo carmine dye spraying view. (b) ESD procedures of this case. Main knife was Dual knife and SB knife Jr was used to assist. (c) ESD specimen and pathological findings (HE staining, cross section, × 40). Adenocarcinoma in high-grade tubulovillous adenoma, pSM (5 mm), budding grade 1, tumor margin negative. Lymph node metastasis was detected after additional surgery.

Figure 2.

Each knife for colorectal ESD and its release year.

Figure 3.

Single balloon sliding tube for colon. This sliding tube is easy to use and improves colonoscope manipulation in proximal colon, flexure or palace where paradoxical movement occurs. (Colorectal Endoscopic Submucosal Dissection Standardization Implementation Working Group.)

INDICATIONS FOR ESD OF COLORECTAL TUMORS

In general, the colorectal tumors that are difficult to remove by en bloc endoscopic mucosal resection (EMR) are large laterally spreading tumors (LST).7 Although LST larger than 20 mm in diameter tend to be removed by piecemeal EMR due to the size limitation of the snare, cutting the adenomatous portion never has significant effects on the pathological examination or curability of the lesion. Granular-type LST showing adenoma or focal cancer in adenoma is an indication for piecemeal EMR under the condition that the cancerous portion is perfectly resected en bloc. In such a procedure, magnifying observation of the pit pattern is essential prior to piecemeal EMR.8

In contrast, indications for colorectal ESD recommended by the Colorectal ESD Standardization Implementation Working Group are as follows (Table 1):1,2,5 (i) lesions difficult to remove en bloc with a snare EMR due to size, such as non-granular LST (particularly pseudo-depressed type), lesions showing a type Vi pit pattern and protruded-type large lesions suspected to be carcinoma; (ii) lesions with fibrosis due to biopsy or peristalsis; (iii) sporadic localized lesions in chronic inflammation such as ulcerative colitis; and (iv) local residual carcinoma after EMR.

Table 1.  Indication of ESD for colorectal tumor by colorectal ESD standardization implementation working group
  • Including granular-type laterally spreading tumors (LST-G), nodular mixed type. EMR, endoscopic mucosal resection.

1. Large sized (>20 mm in diameter) lesions in which en bloc resection using snare EMR is difficult, although it is indicative for endoscopic treatment
 LST-NG, particularly those of the pseudo-depressed type
 Lesions showing VI type pit pattern
 Carcinoma with submucosal infiltration
 Large depressed type lesion
 Large elevated lesion suspected to be carcinoma
2. Mucosal lesions with fibrosis caused by prolapse due to biopsy or peristalsis of the lesions
3. Sporadic localized tumors in chronic inflammation such as ulcerative colitis
4. Local residual early carcinoma after endoscopic resection

However, ESD for lesions with severe fibrosis is technically very difficult.9 To select the best therapy (piecemeal EMR, ESD or surgical resection) in practice, we should consider not only the features of the lesions including clinicopathological aspects and the location but also the skill level of the colonoscopist including ability in scope handling and the predicted duration of the procedure.

Recently, the usefulness of hybrid ESD, which is combination of both ESD and EMR techniques, has been reported for relatively small lesions.10 Hybrid ESD provides the time benefit and technical support of the dissection technique for non-experts in colorectal ESD (Fig. 4).

Figure 4.

(a) Hybrid endoscopic submucosal dissection (ESD with combination use of endoscopic mucosal resection [EMR]) case for non-granular laterally spreading tumors, pseudo-depressed type, Rectsigmoid, 25 mm in diameter. Left, standard colonoscopic view; Right, indigo carmine dye spraying view. (b) Hybrid ESD procedures of this case (as in [a]). Main knife was Dual knife. Subsequently, after ESD procedures EMR technique was applied. (c) Hybrid ESD specimen and pathological findings (HE staining). Well-differentiated adenocarcinoma, pSM (500 µm), ly0, v0, tumor margin negative.

OUTCOMES OF COLORECTAL ESD IN THE PUBLISHED WORK

The PubMed database was used to search for publications through August 2011 related to colorectal ESD using the key words ESD and colon. The MEDLINE database was used to search for publications through August 2011 related to ESD using the above-mentioned key words. A manual search of the citations of relevant articles was also performed. Pertinent studies published in English and Japanese were reviewed. If an institution had published several reports on colorectal ESD, the newest report was selected for the summary of outcomes of colorectal ESD.

A summary of outcomes of colorectal ESD using previous reports from single institution studies is described in Table 2.9,11–22 The overall data of outcomes by a summary of previous reports from single institution studies are described in Table 3. Regarding efficacy, the en bloc resection (endoscopic) and complete en bloc resection (histological) rates were 82.8% (61–98.2%, 2082/2516) and 75.7% (58–95.5%, 1271/1680), respectively. Regarding complications, the perforation and postoperative bleeding rates were 4.7% (1.4–8.2%, 127/2719) and 1.5% (0.5–9.5%, 31/2087), respectively. Local recurrence was detected in 1.2% (0–11%, 9/768) of cases.

Table 2.  Outcome of colorectal ESD by summary of precious reports by a single institution (no multicenter study)
AuthorsYearNo. of casesSize (mm)En bloc resection rate (%)Complete en bloc resection rate (%)ComplicationsLocal recurrence (%)
Perforation (%)Bleeding (%)
  1. The newest report was selected from institutions that published several reports.

Tamegai1120077132.770/71 (98.6%)68/71 (95.6%) 1/71 (1.4%)0/71 (0%)
Hurilstome122007423133/42 (84%)31/42 (70%)1/42 (2.1%)4/42 (9.5%)4/36 (11%)
Fujishiro13200720029.9183/200 (91.5%)141/200 (70.5%)12/200 (6.0%)1/200 (1.0%) 
Zho1420097432.669/74 (93.2%)66/74 (89.2%)6/74 (8.1%)1/74 (1.4%)0/74 (0%)
Isomoto15200929226.8263/292 (90.1%)233/292 (79.8%)23/292 (8.2%)2/292 (0.7%)1/220 (0.5%)
Saito16200940540352/405 (87%) 14/405 (3.5%)4/405 (1.0%) 
Iizuka172009383923/38 (61%)22/38 (58%)3/38 (8%)  
Hotta18201012035112/120 (93.3%)102/200 (85%)9/120 (7.5%)  
Niimi19201031028.9280/310 (90.3%)231/310 (74.5%)15/310 (4.8%)5/310 (1.6%)4/202 (2.0%)
Yoshida20201025029.1217/250 (86.8%)203/250 (81.2%)15/250 (6%)6/250 (2.4%) 
Toyonaga21201051229503/512 (98.2%) 9/512 (1.8%)8/512 (1.6%) 
Matsumoto9201020332.4 174/203 (85.7%)14/203 (6.9%)  
Uraoka22201120239.9185/202 (91.6%) 5/202 (2.5%)1/202 (0.5%)0/165 (0%)
Table 3.  Overall data from outcome of colorectal ESD by summary of previous reports by single institution (non-multicenter study)
Each itemOverall dataRange
  1. Data from 2719 cases in 13 institutions described in Table 1.

En bloc resection82.8% (2082/2516)61–98.2%
Complete en bloc resection75.7% (1271/1680)58–95.6%
Perforation4.7% (127/2719)1.4–8.2%
Postoperative bleeding1.5% (31/2087)0.5–9.5%
Local recurrence1.2% (9/768)0–11%

Outcomes of colorectal ESD by a summary of previous reports from multicenter studies are shown in Table 4.5,23–26 Although these reports include data from both the early period to more recent period of colorectal ESD without considering the learning curve, en bloc resection (endoscopic) and complete en bloc resection (histological) rates were 88.8% and 83.8%, respectively. The perforation rate was 3.3–14.0%. The delayed perforation rate was 0.4–0.7%. Postoperative bleeding occurred in 1.5–2.1% of cases.

Table 4.  Overall data from outcome of colorectal ESD by summary of previous multicenter study reports
AuthorsYearsNo. of institutionsNo. of casesEn block resectionComplete en block resectionComplication
PerforationDelayed perforationPost-ESD bleeding
  • Intraoperative perforation 4.1%.

Tsuda S232006191367  5.4%0.6%2.1%
Taku K242007443  14.0%  
Tanaka S520101948303 83.8%4.8%0.7%1.6%
Saito Y25201010111188% 4.9%0.4%1.5%
Oka S26201039688  3.3% 1.7%

OUTCOMES OF COLORECTAL ESD IN A MULTICENTER PROSPECTIVE COHORT STUDY BY THE JAPANESE SOCIETY FOR CANCER OF THE COLON AND RECTUM (JSCCR)

Partial outcomes of colorectal ESD in a multicenter prospective cohort study by the JSCCR, the ‘Prospective multicenter cohort study on local curability and complication in each endoscopic treatment for colorectal tumor larger than 20 mm’ was reported at UEGW 2011 (Stockholm).27 Briefly, the en bloc resection and perforation rates of 805 cases treated with ESD at 19 institutions familiar with colorectal EMR/ESD were 95% and 1.4% for lesions 20–29 mm in size, 96% and 2.7% for lesions 29–39 mm in size, and 93% and 1.5% for lesions more than 40 mm in size, respectively. Detailed data are now in submission.

MULTICENTER PROSPECTIVE COHORT STUDY BY THE JAPAN GASTROENTEROLOGICAL ENDOSCOPY SOCIETY (JGES)

At present, colorectal ESD is performed as an advanced medical treatment without national health insurance coverage. Indications for colorectal ESD as an advanced medical treatment in Japan are shown in Table 5. From September 2010, colorectal ESD cases performed as an advanced medical treatment were registered in a multicenter prospective cohort study by the JGES to obtain medical remuneration from national health insurance using data from this study (efficacy and safety). More than 1500 cases have already been entered into this study by 60 institutions in Japan. In the very near future, the outcomes of this study will be reported.

Table 5.  Indications of colorectal ESD as ‘Advanced medical treatment’ in Japan
  1. EMR, endoscopic mucosal resection; EUS, endoscopic ultrasonography.

1. Early carcinoma larger than 20 mm which is difficult to resect en bloc by EMR. Also, curability should be expected by magnification or EUS.
2. Adenoma showing non-lifting sign
3. Residual lesion after EMR larger than 10 mm, which is difficult to resect by EMR

DISCUSSION

As a result of the improvements in ESD devices, peripheral equipment and the development of the colorectal ESD technique, use of colorectal ESD has spread extensively in Japan. As shown by the outcomes in our summary of the published work and in the study by the JSCCR, colorectal ESD has already become a not too difficult or dangerous technique. Even if perforation occurs in an ESD procedure, it is a microperforation and patients can be treated conservatively by closure of the hole with a clip. In the very near future, JGES will apply to the Japanese government to provide the remuneration from national health insurance. We expect that colorectal ESD will be a common method for large early colorectal carcinoma that cannot be treated by en bloc EMR.

However, because colorectal ESD takes longer, requires more labor and costs more than EMR, we should strictly determine the indications for colorectal ESD (Table 1).1,2,5 Because tumors of the colon and rectum differ from tumors of the upper gastrointestinal tract, there are many benign adenomatous lesions in the colon and rectum that must be distinguished from carcinoma.1,2,5,28–30 Adenomatous lesions can be treated by piecemeal EMR, and piecemeal EMR is sufficient for treatment of adenoma.1,2,5,28–30 Indeed, good outcome was shown in the published work.10,28,31 From this point of view, exact diagnosis with magnification (pit pattern diagnosis8 or image-enhanced endoscopy by narrow-band imaging and flexible spectral imaging color enhancement)32–36 prior to endoscopic treatment is very important to distinguish among adenoma, cancer in adenoma, and cancer without adenomatous component. After a detailed examination prior to endoscopic treatment and with this information, we should select adequate therapeutic methods considering curability, safety, simplicity and cost–benefit. In addition, we should consider the qualifications for colorectal ESD according to the endoscopic skill and experience in colorectal ESD. Although live demonstrations and hands-on seminars of ESD using animal models have been periodically held in Japan, establishment of an effective training system for colorectal ESD will be increasingly important in the future.

CONFLICT OF INTEREST

None declared.

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