How to establish endoscopic submucosal dissection in Western countries

Table 1 Indications for endoscopic en-bloc resection of gastrointestinal neoplasias (modified from[6])

Organ	Indications for …	Ref.
Stomach	ESD - classical indications1	[1,4,5,13]
	mucosal adenocarcinoma; intestinal type G1 or G2, size d ≤ 2 cm, no ulcer
	ESD - expanded indications2
	adenocarcinoma, intestinal type, G1 or G2, any size without ulcer/adenocarcinoma, intestinal type, G1 or G2, sm-invasive < 500 μm/adenocarcinoma, intestinal type, G1 or G2, d ≤ 3 cm, with ulcer/adenocarcinoma diffuse type, G3 or G4, size d ≤ 2 cm, no ulcer
Esophagus	ESD - classical indications1	[5,8,9,12,14,15]
	SCC type 0-IIb (HGIN or G1, G2), intramucosal (m1, m2), any size
	Barrett adenoca. type 0-II (G1, G2), intramucosal (m1, LPM), no ulcer
	ESD - expanded indications2
	SCC type 0-II (HGIN, G1, G2) slightly invasive (m3, sm < 200 μm), any size3, clinical N 0
	Barrett adenocarcinoma type 0-II (HGIN or G1, G2), mucosal ( ≤ MM), clinical N 0
Colorectum	ESD Indications	[5,10,11,16,64]
	Any neoplasias > 20 mm in diameter without signs of deep submucosal invasion, indicative for en-bloc resection and unsuitable for EMR en-bloc:
	LST-granular type d ≥ 4 cm (villous adenoma +/- HGIN)4
	LST-nongranular type d ≥ 2 cm
	Mucosal carcinoma (HGIN, G1 or G2), or superficially sm-invasive5
	Depressed-type neoplasias (0-IIc)
	Neoplasias type 0-I or 0-II with pit pattern type VI (irregular)
	Sporadic localized neoplasias in chronic ulcerative colitis
	Colorectal carcinoids of diameter < 20 mm (EMR, when diameter < 10 mm)

¹Indications with risk of LNM < 1%;

²Indications with risk of LNM or systemic M < 4%;

³Increased risk for stricture formation, when ESD extends for ≥ 70% of circumference;

⁴LST-granular type may also be resected in piecemeal fashion, the larger nodule resected first[10];

⁵SM1 invasion of ≤ 1000 μm. LNM: Lymph node metastasis; ESD: Endoscopic submucosal dissection.

Table 2 Criteria of curative endoscopic resection en-bloc in esophagus, stomach, and colorectum (modified from[17])

Stomach

Guideline criteria1

m-ca, diff. type, ly (-), v (-), and Ul (-) and ≤ 2 cm in size

Expanded criteria2

m-ca, diff. type, ly (-), v (-), Ul (-) and any size > 2 cm

m-ca, diff. type, ly (-), v (-), Ul (+) and ≤ 3 cm in size

sm 1-ca (invasion depth < 500 μm3), diff. type, ly (-), v (-)

m-ca, undifferentiated type (G3), ly (-), v (-), Ul (-) and size < 2 cm

Esophagus (squamous lesions only)

Guideline criteria1

pT1a-EP-ca/pT1a-LPM-ca

Expanded criteria2

pT1a-MM-ca, ly (-), v (-), diff. type, expansive growth, ly (-), v (-)

cT1b-sm-ca (invasion < 200 μm3), ly (-), v (-), infiltrative growth pattern, expansive, diff. type, ly (-), v (-)

Colorectum

Guideline criteria1

m-ca, diff. type, ly (-), v (-)

sm-ca (< 1000 μm3), diff. type, ly (-), v (-)

¹Indications with risk of LNM < 1%;

²Indications with risk of LNM or systemic M < 4%;

³Measured as distance of maximum vertical invasion below MM. m: Mucosal; ca: Cancer; diff: Differentiated; ly: Lymphatic invasion; v: Vascular invasion; Ul: Ulceration; sm: Submucosal; EP: Epithelium; LPM: Lamina propria mucosae; MM: Muscularis mucosae.

Table 3 Organ-specific outcome of endoscopic submucosal dissection (curative intention) for Western prospective studies

Ref.	Malignant neo-plasia type6, n	ESD, n	Resection en-bloc, %	Resection curative6, %	Complications, %	Surgery, %	Mortal., %	Recurrence, %	Follow-up (med.) yr	DFS, %/yr
Gastric ESD
Cardoso et al[46], 2008	GC 15	15	80	74	20	8	0	8	1	91/1
Catalano et al[47], 2009	GC 12	12	92	92	16	8	0	8	2.5	92/2
Probst et al[49], 2010	GC 66	91	87	72	10.6	11	0	5.6	2.3	96.7/2
Schumacher et al[50], 2012	GC 21	28	90	64	20	7	3.4	11	2	100/2
Pimentel-Nunes et al[51], 2014	GC 128	136	94	82	13	7	0	7	3.2	100/3
median [range]			90 [80-94]	73 [64-92]	15 [11-20]	8 [7-11]	0 [3.4]	8 [5-11]	2.3 [1-3]	97 [91-100]/2
Esophageal ESD
Repici et al[52], 2010	SCC 20	20	100	90	15	10	0	0	1.5	100/1.5
Neuhaus et al[53], 2012	AC 26	29	90	39	17	0	0	4	1.5	96/1.5
Arantes et al[54], 2012	AC 25	25	92	80	12	4	0	8	1.5	96/1.5
Höbel et al[56], 2014	AC 22	22	96	77	27	23	0	6	1.6	94/1.6
Chevaux et al[55], 2015	AC and HG 66	73	90	64	7 (+603)	10	0 (31)	(105)	1.8	92/2
Probst et al[57], 2015	AC 87	87	95	72 (844)	12.6	6	0 (21)	5	2.0	98/2
Probst et al[57], 2015	SCC 24	24	100	46 (724)	12.6	0	0 (41)	4	3.2	96/3
median [range]			95 [90-100]	72 [39-90]	16 [12-66]	6 [0-23]	0 [0-4]	4 [0-8]	1.6 [1.5-3.2]	96 [94-100]/2
Colorectal ESD
Probst et al[59], 2012	Rectosigm. LST	76	82	-	9.2	15	0	n.g.	2.0	100/2
	14 CRC		86	7		(792)		0
Iacopini et al[58], 2012	Colorectal LST	60	68	-	10	20	0	n.g.	n.g.	n.g.
	29 CRC			72	n.g.	(282)
Repici et al[60], 2013	Rectal LST	40	90	-	7.5	5	0	2.5	0.5	100/0.5
	8 RC			75	n.g.	(252)
Thorlacius et al[61], 2013	Colorectal LST	29	72	76	10	10	0	n.g.	< 0.5	n.g.
	10 HG and CRC			80		(202)
Berr et al[38], 2014	Colorectal LST	39	76	-	17	3	0	LG 9	1.5	100/1.5
	12 HG		83	83		(02)		HG 0		100/1.5
median [range]			83 [72-90]	75 [7-83]	10 [7.5-17]	10 [3-20]	0	8 [2.5-9]	1.5 [0.5-2]	100/1.5

¹Rate (%) due to cancer progression;

²Surgery (%) for malignant lesion after ESD;

³Plus stenoses (%);

⁴Rate (%) of R0 resection;

⁵Metachronous HGIN or cancer;

⁶Curative resection does only apply for malignant neoplasias (cancer -/+ HGIN). AC: Adenocarcinoma; CRC: Colorectal carcinoma; GC: Gastric cancer; HG/LG: High/low-grade intraepithelial neoplasia; RC: Rectal carcinoma; SCC: Squamous cell cancer; DFS: Disease-free survival rate; n.g.: Not given; pmEMR: Piecemeal EMR.

Table 4 Principles for establishing endoscopic submucosal dissection by an untutored learning curve (modified from[38])

Evaluate the lesion during prior endoscopy for ESD indication and resection strategy

Avoid risk of any R2 resection of cancer (no signs for deep submucosal invasion!)

Avoid high risk lesions (> 5 cm diameter, or in fornix and cardia, duodenum, colonic flexures)

Safety comes first, procedure time of ESD is of minor importance in the beginning

Only cut tissue or fibers in submucosa that you clearly see and have identified

Keep the vision field clear, prevent and immediately stop bleeding

Close any perforation immediately by endoscopic clipping on expert level

Complete any started ESD procedure with intention for safe, curative resection

Guide personally the patient pre-ESD (informed consent) and post-ESD (for any complication)

Only a single endoscopist per unit should do untutored ESD until he is on competence level1

Document all entire ESD procedures on DVD recordings (for evidence and error analysis)

Follow-up short-term and long-term (center Registry), trend in dozens

¹Performance of 20 consecutive ESD procedures with < 10% complications. ESD: Endoscopic submucosal dissection.