Introduction of endoscopic submucosal dissection in the West

Table 1 Endoscopic mucosal resection vs endoscopic submucosal dissection for early Barrett’s and esophagogastric junction neoplasia

	ESD-6 Asian studies		EMR-10 Western studies		Odds ratio	P-value
Outcome	No. of studies	n (%)	No. of studies	n (%)	(95%CI)
Recurrence rate	6	1/333 (0.3)	5	10/380 (2.6)	8.55 (0.91, 80.0)	0.06
Perforation	6	5/335 (1.5)	9	8/686 (1.2)	1.07 (0.20, 5.62)	0.94
Delayed bleeding	6	7/335 (2.1)	9	8/686 (1.2)	0.46 (0.12, 1.75)	0.26
Stricture	5	7/207 (3.4)	7	3/456 (0.7)	0.21 (0.03, 1.41)	0.11
Method	No. of studies		Pooled procedure time (95%CI)
EMR	2		36.7 (34.5, 38.9)
ESD	5		83.3 (57.4, 109.2)

Modified from Komeda et al[7]. EMR: Endoscopic mucosal resection; ESD: Endoscopic submucosal dissection.

Table 2 Endoscopic submucosal dissection for Barrett’s high-grade intraepithelial neoplasia and early adenocarcinoma

Reference	Chevaux et al[9]	Kagemento et al [10]	Höbel et al [11]	Tergheggen et al [8]
Subjects	75	19	22	17
Study design	Retrospective	Retrospective	Retrospective	Prospective
Rates of resection
En-bloc	90%	100%	96%	100%
R0 resection rate	64%	85%	82%	59%
Curative rate	64%	65%	77%	93%
Adverse events
Bleeding	3%	4%	9%	0%
Perforation	4%	0%	5%	12%
Stricture	60%	15%	14%	0%

Modified from Terheggen et al[7].

Table 3 Endoscopic submucosal dissection for early gastric cancer in the West

Reference	N	Follow-up (yr)	Mortality (%)	En-bloc resection (%)	Curative resection (%)	Surgery (%)	Recurrence (%)
Cardoso et al[16]	15	1	0	80	74	8	8
Catalano et al[17]	12	2.5	0	92	92	8	8
Probst et al[18]	91	2.3	0	87	72	12	5.6
Schumacher et al[19]	28	2	3.4	90	64	7	11
Pimental-Nunes et al[20]	136	2.2	0	94	82	7	7

Modified from Oyama et al[2].

Table 4 Endoscopic submucosal dissection for early gastric cancer

Histology	Depth
	Mucosal cancer				Submucosal cancer
	No ulceration		Ulcerated		SM1	SM2
	≤ 20	> 20	≤ 30	> 30	≤ 30	Any size
Intestinal	1	3	3	4	3	4
Diffuse	2	4	4	4	4	4

¹Guideline criteria for ESD;

²Consider surgery;

³Expanded criteria for ESD;

⁴Surgery (gastrectomy + lymph node dissection). ESD: Endoscopic submucosal dissection.

Table 5 Major Western endoscopic submucosal dissection series for early gastric cancer n (%)

	Guideline criteria	Expanded criteria	Out of indication	P-value
179 subjects	53 subjects	87 subjects	30 subjects
Post ESD endoscopic follow-up	53/53 (100)	84/87 (97)	27/39 (69)	< 0.001
Follow-up median (mo)	51	56	36	NS
Curative resection	47/53 (89)	65/87 (75)	0	0.07
Local recurrence	0	4/84 (5)	3/27 (11)	0.06
Post ESD surgery	0	3/87 (3)	12/39 (31)	< 0.001
Metastases	0	1/84 (1)	3/27 (11)	0.005
Gastric cancer mortality	0	0	3 (8)	0.004
All-cause mortality	7 (13)	16 (18)	11 (28)	0.19

One hundred and seventy-nine ESD procedures for EGC over 12 years-about 15/year (modest compared to Asian centers). This Western center’s learning curve: 1^st block of ESD’s (1-96) compared to 2^nd block (97-191). R0 resection increased from 60% (57/96) to 93% (88/95) (P < 0.001). Median procedure time decreased from 148 to 110 min (P < 0.001). Modified from Probst et al[25]. ESD: Endoscopic submucosal dissection; NS: Not significant; EGC: Early gastric cancer.

Table 6 Cost analysis-endoscopic submucosal dissection vs endoscopic mucosal resection for colorectal lesions

ESD vs Wide-field EMR for large sessile and lateral spreading lesions > 2 cm: Cost analysis

Selective ESD prevented 19 additional surgeries per 1000 cases at slightly lower cost compared with WF-EMR

U-ESD could prevent an additional 13 surgeries per 1000 cases compared with S-ESD but at substantially increased cost of > 21000 dollars (Australian) per surgery avoided

Expanded ESD criteria (Japanese Gastrointestinal Endoscopy Society) adding mainly granular lesions > 4 cm added little additional benefit

Authors stated U-ESD is “unjustified” given WF-EMR effectiveness for benign lesions of LR-SMIC

Subgroup analysis of only rectal lesions concluded WF-EMR including trans-anal resection was as effective as S-ESD and still less costly

Because of the higher prevalence of SMIC in the rectum, the incremental cost per surgery avoided by U-ESD decreased to $87066 and dropped to $32132 among non-granular rectal lesions. U-ESD became the least costly and most effective strategy among higher risk non-granular Paris 0-is rectal lateral spreading lesions

Study design: Selective ESD strategy was employed for lesions suspicious for SMIC-all others had WF-EMR. Pathology after ESD revealing high - risk SMIC necessitated surgery. LR-SMIC on pathology at the ESD were considered cured

After Behin. Gut 2017. U-ESD: Universal ESD; ESD: Endoscopic submucosal dissection; EMR: Endoscopic mucosal resection; LR-SMIC: Low prevalence of low risk submucosal invasive cancer; WF-EMR: Wide field endoscopic mucosal resection; S-ESD: Selective endoscopic submucosal dissection; SMIC:submucosal invasive cancer.

Table 7 Caveats for the endoscopic submucosal dissection pioneer

Start clinical ESD only after extensive pre-clinical training

Start with easier lesions

Avoid “unprincipled ESD”

Record and monitor closely outcomes and complications- consider registry and videos

Be familiar with techniques for endoscopic management of complications

The main complications (perforation and bleeding) can almost always be managed (or even prevented in the case of bleeding) by skillful application of clips and coagulation

Experience with endoscopic clip placement and coagulation grasper application is essential (experience with endoscopic suturing is highly desirable)

Avoid mistakes in selecting and scheduling cases-many referral reports lack detailed information on morphology, size, location, prior manipulation

Morphology (e.g., Paris classification) may suggest a more advanced lesions that was appreciated on the index endoscopy and biopsy that may require expedited scheduling

Index biopsies may be misleading (obtained from the periphery rather than depressed areas of 2c or 1s lesions missing a carcinoma)

Biopsies yielding only dysplasia may result in a publicly delayed resection of cancer

Concordance of biopsy results and ultimate post-resection pathology is fair at best

EDUCATE your referring physicians-AVOID inappropriate India ink tattooing and “partial snare resections”/hot forceps/jumbo forceps for “diagnosis or “attempted” hasty resections (tackling lesions where probability of complete EMR is low)

Lack of experience in delineating early GI cancer main lead to excessive sampling biopsies

DISCOURAGE APC to” vaporize “grossly” evident residual tumor or aggressive/many biopsies of delicate flat lesions (SSA’s)

ENCOURAGE: (1) detailed descriptions: size, morphology; (2) lots of pictures; (3) giving print out with color pictures to the patient and d) having referring physicians transit “money” shots of lesion to you

Put post - resection specimens on corkboard and educate pathologist about specifics of resection

Pathologists should properly orient specimens with ≤ 2 mm slices

Pathology report should comment on adequacy of resection including deep and lateral margins with measurement of submucosal invasion with micrometer measurements as well as the differentiation (G1-G3)

Optimally there should be desmin staining of the muscularis mucosa noting the pattern of SM invasion, e.g., budding

Comment should be made regarding lymphovascular invasion with elastin Van Gieson stain to delineate venules and the D2 – 40 immunostain for lymphatics (important)

Multidisciplinary input and communication including nursing, technicians, anesthesiologists, surgeons and oncologists

The patient should be evaluated as dictated by medical history by internists, cardiology and pulmonary medicine with particular attention to anticoagulants and antiplatelet drugs

Ergonomic considerations are given to both ESD operator and patient

ESD: Endoscopic submucosal dissection; GI: Gastrointestinal.

Table 8 Benefits of institution endoscopic submucosal dissection program

Potential benefit in avoiding surgery/organ resection

“Downstream revenue “from increased services and subsequent referral to surgery/oncology of patients (possibly up to 20% of ESD’s performed)

Enhancement of overall institutional prestige

ESD is a necessity for any institution purporting to be a tertiary referral center for luminal GI tract

Enhanced recruitment of trainees and faculty after establishment of ESD program

ESD: Endoscopic submucosal dissection; GI: Gastrointestinal.

Table 9 Western Center initial endoscopic submucosal dissection series n (%)

EMNS		SETs
Total Lesions	38 (43)	Total lesions	51 (57)
Size, mean millimeters (range)	26 (5-90)	Size, mean millimeters (range)	18 (8-55)
Complete en-bloc resection (R0 deep + lateral margins)	20 (53)	Complete en-bloc resection (completeness assessed endoscopically)	38 (75)
		Complete 2-piece resection	5 (10)
		incomplete resection	8 (15)
Histologic diagnosis		Histologic diagnosis
T1 carcinomas/adenomas with HGD	16 (42)	GIST	12 (23)
Adenomas w/o HGD	10 (26)	Pancreatic rests	11 (21)
No residual adenoma granulation tissue	11 (29)	Lipomas	8 (16)
Unclassified	1 (3)	Carcinoids	6 (12)
		Granular cell tumors	3 (6)
		Leiomyomas	8 (16)
		Other	3 (6)

SETs: Subepithelial tumors; EMNS: Early mucosal neoplasm; GIST: Gastrointestinal stromal tumors; HGD: High grade dysplasia.