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

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CURRENT STATUS AND FUTURE PERSPECTIVES OF ENDOSCOPICSUBMUCOSAL DISSECTION FOR COLORECTAL TUMORS

Shinji Tanaka,1 Motomi Terasaki,2 Hiroyuki Kanao,1 Shiro Oka1 and Kazuaki Chayama2

Departments of 1Endoscopy and 2Gastroenterology and Metabolism, Hiroshima University Hospital, Hiroshima, Japan

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 gastrointestinaltract.Although the use of colorectal ESD has been gradually spreading with the development of numerous devices, ESD hasnot yet been fully established as a standard therapeutic method for colorectal lesions. Currently, colorectal ESD isperformed as an ‘advanced medical treatment’ without national health insurance coverage.With the recent accumulation ofnumerous cases, the safety and simplicity of colorectal ESD have improved remarkably. Currently in Japan, a prospectivemulticenter cohort study organized by the Japan Gastroenterological Endoscopy Society is ongoing to clarify the safety andefficacy of colorectal ESD to obtain remuneration from national health insurance. In this report, we showed the outcomeregarding safety and efficacy of colorectal ESD through a review of the published work. Of 2719 cases with colorectal ESDat 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 enoughto be closed endoscopically by clips in most of the cases and treated conservatively. In the near future, colorectal ESD willbe a common therapeutic method for early colorectal carcinoma.

Key words: colorectal tumor, endoscopic submucosal dissection, ESD, hybrid ESD.

INTRODUCTION

Endoscopic submucosal dissection (ESD) enables en blocresection of a lesion irrespective of its size.1,2 Accurate histo-pathological diagnosis can be attained using ESD, and theaffected organ can be preserved after the treatment. There-fore, ESD is widely used for the treatment of carcinoma ofthe upper gastrointestinal tract, particularly in the stomach,3,4

and in Japan, national health insurance covers the expense ofESD as a therapeutic procedure for early gastric and esoph-ageal carcinoma. ESD has also been increasingly applied tothe colon and rectum (Fig. 1). Although ESD has not yetbeen recognized as a conventional therapeutic procedure forearly colorectal carcinoma due to its technical difficulty, it hasbeen made easier and safer by recent advances both in equip-ment (Figs 2,3) and technique, as well as the experience ofmany cases.5 In addition, the use of a carbon dioxide (CO2)insufflation system has made it easier to perform colorectalESD.2,6 CO2 can be absorbed by tissue at a speed more than100 times that of room air. The use of this system candecrease colonic distension during ESD due to air insuffla-tion. In addition, even when perforation occurs and the holeis closed with a clip, the risk of peritonitis is remarkablydecreased.6 In this chapter, we will describe the indicationsfor 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.

INDICATIONS FOR ESD OF COLORECTALTUMORS

In general, the colorectal tumors that are difficult to removeby en bloc endoscopic mucosal resection (EMR) are largelaterally spreading tumors (LST).7 Although LST larger than20 mm in diameter tend to be removed by piecemeal EMRdue to the size limitation of the snare, cutting the adenoma-tous portion never has significant effects on the pathologicalexamination or curability of the lesion. Granular-type LSTshowing adenoma or focal cancer in adenoma is an indicationfor piecemeal EMR under the condition that the cancerousportion is perfectly resected en bloc. In such a procedure,magnifying observation of the pit pattern is essential prior topiecemeal EMR.8

In contrast, indications for colorectal ESD recommendedby the Colorectal ESD Standardization ImplementationWorking Group are as follows (Table 1):1,2,5 (i) lesions diffi-cult to remove en bloc with a snare EMR due to size, such asnon-granular LST (particularly pseudo-depressed type),lesions showing a type Vi pit pattern and protruded-typelarge lesions suspected to be carcinoma; (ii) lesions withfibrosis due to biopsy or peristalsis; (iii) sporadic localizedlesions in chronic inflammation such as ulcerative colitis; and(iv) local residual carcinoma after EMR.

However, ESD for lesions with severe fibrosis is technicallyvery difficult.9 To select the best therapy (piecemeal EMR,

Correspondence: Shinji Tanaka, Department of Endoscopy,Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551,Japan. Email: [email protected]

Received 9 December 2011; accepted 11 January 2012.

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Digestive Endoscopy (2012) 24 (Suppl. 1), 73–79 doi:10.1111/j.1443-1661.2012.01252.x

© 2012 The AuthorsDigestive Endoscopy © 2012 Japan Gastroenterological Endoscopy Society

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c

Fig. 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 ofthis 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.

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Fig. 2. Each knife for colorectal ESD and its release year.

Fig. 3. Single balloon sliding tube forcolon. This sliding tube is easy to useand improves colonoscope manipula-tion in proximal colon, flexure or palacewhere paradoxical movement occurs.(Colorectal Endoscopic SubmucosalDissection Standardization Implemen-tation Working Group.)

Table 1. Indication of ESD for colorectal tumor by colorectal ESD standardization implementation working group

1. Large sized (>20 mm in diameter) lesions in which en bloc resection using snare EMR is difficult, although it is indicative forendoscopic treatment

LST-NG, particularly those of the pseudo-depressed typeLesions showing VI type pit patternCarcinoma with submucosal infiltrationLarge depressed type lesionLarge elevated lesion suspected to be carcinoma†

2. Mucosal lesions with fibrosis caused by prolapse due to biopsy or peristalsis of the lesions3. Sporadic localized tumors in chronic inflammation such as ulcerative colitis4. Local residual early carcinoma after endoscopic resection

†Including granular-type laterally spreading tumors (LST-G), nodular mixed type. EMR, endoscopic mucosal resection.

ESD FOR COLORECTAL TUMOR 75


MM

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c

SMSM

Fig. 4. (a) Hybrid endoscopic submucosal dissection (ESD with combination use of endoscopic mucosal resection [EMR]) case fornon-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 mm), ly0, v0, tumor margin negative.

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ESD or surgical resection) in practice, we shouldconsider not only the features of the lesions including clinico-pathological aspects and the location but also the skill level ofthe colonoscopist including ability in scope handling and thepredicted duration of the procedure.

Recently, the usefulness of hybrid ESD, which is combina-tion of both ESD and EMR techniques, has been reported forrelatively small lesions.10 Hybrid ESD provides the timebenefit and technical support of the dissection technique fornon-experts in colorectal ESD (Fig. 4).

OUTCOMES OF COLORECTAL ESD IN THEPUBLISHED WORK

The PubMed database was used to search for publica-tions through August 2011 related to colorectal ESDusing the key words ESD and colon. The MEDLINE data-base was used to search for publications through August2011 related to ESD using the above-mentioned key words.A manual search of the citations of relevant articles wasalso performed. Pertinent studies published in Englishand Japanese were reviewed. If an institution had pub-lished several reports on colorectal ESD, the newest reportwas selected for the summary of outcomes of colorectalESD.

A summary of outcomes of colorectal ESD using previousreports from single institution studies is described inTable 2.9,11–22 The overall data of outcomes by a summary ofprevious reports from single institution studies are describedin Table 3. Regarding efficacy, the en bloc resection (endo-scopic) and complete en bloc resection (histological) rateswere 82.8% (61–98.2%, 2082/2516) and 75.7% (58–95.5%,1271/1680), respectively. Regarding complications, the perfo-ration 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) ofcases.

Outcomes of colorectal ESD by a summary of previousreports 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 with-out considering the learning curve, en bloc resection(endoscopic) and complete en bloc resection (histological)rates were 88.8% and 83.8%, respectively. The perforationrate was 3.3–14.0%. The delayed perforation rate was0.4–0.7%. Postoperative bleeding occurred in 1.5–2.1% ofcases.

OUTCOMES OF COLORECTAL ESD INA MULTICENTER PROSPECTIVE COHORT

STUDY BY THE JAPANESE SOCIETYFOR CANCER OF THE COLON AND

RECTUM (JSCCR)

Partial outcomes of colorectal ESD in a multicenter prospec-tive cohort study by the JSCCR, the ‘Prospective multicentercohort study on local curability and complication in eachendoscopic treatment for colorectal tumor larger than20 mm’ was reported at UEGW 2011 (Stockholm).27 Briefly,the en bloc resection and perforation rates of 805 casestreated with ESD at 19 institutions familiar with colorectalEMR/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% and1.5% for lesions more than 40 mm in size, respectively.Detailed data are now in submission.

Table 2. Outcome of colorectal ESD by summary of precious reports by a single institution (no multicenter study)

Authors Year No. ofcases

Size(mm)

En bloc resectionrate (%)

Complete en blocresection rate (%)

Complications Local recurrence(%)Perforation (%) Bleeding (%)

Tamegai11 2007 71 32.7 70/71 (98.6%) 68/71 (95.6%) 1/71 (1.4%) 0/71 (0%)Hurilstome12 2007 42 31 33/42 (84%) 31/42 (70%) 1/42 (2.1%) 4/42 (9.5%) 4/36 (11%)Fujishiro13 2007 200 29.9 183/200 (91.5%) 141/200 (70.5%) 12/200 (6.0%) 1/200 (1.0%)Zho14 2009 74 32.6 69/74 (93.2%) 66/74 (89.2%) 6/74 (8.1%) 1/74 (1.4%) 0/74 (0%)Isomoto15 2009 292 26.8 263/292 (90.1%) 233/292 (79.8%) 23/292 (8.2%) 2/292 (0.7%) 1/220 (0.5%)Saito16 2009 405 40 352/405 (87%) 14/405 (3.5%) 4/405 (1.0%)Iizuka17 2009 38 39 23/38 (61%) 22/38 (58%) 3/38 (8%)Hotta18 2010 120 35 112/120 (93.3%) 102/200 (85%) 9/120 (7.5%)Niimi19 2010 310 28.9 280/310 (90.3%) 231/310 (74.5%) 15/310 (4.8%) 5/310 (1.6%) 4/202 (2.0%)Yoshida20 2010 250 29.1 217/250 (86.8%) 203/250 (81.2%) 15/250 (6%) 6/250 (2.4%)Toyonaga21 2010 512 29 503/512 (98.2%) 9/512 (1.8%) 8/512 (1.6%)Matsumoto9 2010 203 32.4 174/203 (85.7%) 14/203 (6.9%)Uraoka22 2011 202 39.9 185/202 (91.6%) 5/202 (2.5%) 1/202 (0.5%) 0/165 (0%)

The newest report was selected from institutions that published several reports.

Table 3. Overall data from outcome of colorectal ESD bysummary of previous reports by single institution (non-multicenter study)

Each item Overall data Range

En bloc resection 82.8% (2082/2516) 61–98.2%Complete en bloc resection 75.7% (1271/1680) 58–95.6%Perforation 4.7% (127/2719) 1.4–8.2%Postoperative bleeding 1.5% (31/2087) 0.5–9.5%Local recurrence 1.2% (9/768) 0–11%

Data from 2719 cases in 13 institutions described in Table 1.



MULTICENTER PROSPECTIVE COHORTSTUDY BY THE JAPAN

GASTROENTEROLOGICAL ENDOSCOPYSOCIETY (JGES)

At present, colorectal ESD is performed as an advancedmedical treatment without national health insurance cover-age. Indications for colorectal ESD as an advanced medicaltreatment in Japan are shown in Table 5. From September2010, colorectal ESD cases performed as an advancedmedical treatment were registered in a multicenter prospec-tive cohort study by the JGES to obtain medical remunera-tion from national health insurance using data from thisstudy (efficacy and safety). More than 1500 cases havealready been entered into this study by 60 institutions inJapan. In the very near future, the outcomes of this study willbe reported.

DISCUSSION

As a result of the improvements in ESD devices, peripheralequipment and the development of the colorectal ESD tech-nique, use of colorectal ESD has spread extensively in Japan.As shown by the outcomes in our summary of the publishedwork and in the study by the JSCCR, colorectal ESD hasalready become a not too difficult or dangerous technique.Even if perforation occurs in an ESD procedure, it is amicroperforation and patients can be treated conservativelyby closure of the hole with a clip. In the very near future,JGES will apply to the Japanese government to provide theremuneration from national health insurance.We expect thatcolorectal ESD will be a common method for large earlycolorectal carcinoma that cannot be treated by en blocEMR.

However, because colorectal ESD takes longer, requiresmore 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 ofthe upper gastrointestinal tract, there are many benignadenomatous lesions in the colon and rectum that must bedistinguished from carcinoma.1,2,5,28–30 Adenomatous lesionscan be treated by piecemeal EMR, and piecemeal EMR issufficient for treatment of adenoma.1,2,5,28–30 Indeed, goodoutcome was shown in the published work.10,28,31 From thispoint of view, exact diagnosis with magnification (pit patterndiagnosis8 or image-enhanced endoscopy by narrow-bandimaging and flexible spectral imaging color enhancement)32–36

prior to endoscopic treatment is very important to distinguishamong adenoma, cancer in adenoma, and cancer withoutadenomatous component. After a detailed examinationprior to endoscopic treatment and with this information,we should select adequate therapeutic methods consideringcurability, safety, simplicity and cost–benefit. In addition,we should consider the qualifications for colorectalESD according to the endoscopic skill and experience incolorectal ESD. Although live demonstrations and hands-onseminars of ESD using animal models have been periodicallyheld in Japan,establishment of an effective training system forcolorectal ESD will be increasingly important in the future.

CONFLICT OF INTEREST

None declared.

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Table 4. Overall data from outcome of colorectal ESD by summary of previous multicenter study reports

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Table 5. Indications of colorectal ESD as ‘Advanced medicaltreatment’ in Japan

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

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