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Institution

How to treat early gastric cancer? Endoscopy

Cliniques universitaires Saint-Luc, Brussels Université catholique de Louvain

Pierre H. Deprez

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Background

• Diagnostic or therapeutic purpose – Superficial tumor – Negligible risk for LN

metastasis • Detection: HRE • Definition of size: NBI/chromo • Deep margins? Paris

classification, EUS • Histological types: biopsies (but

not too many…) • Operating time : 2h for a

beginner, 40min for an expert • Technique: knives, submucosal

cushion,CO2,… • Expert pathologist

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Safety standards

• Good knowledge of

– Indications

– ESD Devices

– Injection Solutions

– Use of Electrosurgical Unit

– Use of clips, endoloops, macroclips

• CO2 insufflation

• Sedation with intubation for UGI ESDs

• Hospitalization

• (Antibiotics)

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Recent guidelines

Japanese guidelines

• In general, endoscopic resection should be carried out when the likelihood of lymph node metastasis is extremely low, and lesion size and site are amenable to resection en bloc (evidence level V, grade of recommendation C1)

• Endoscopic therapy is absolutely indicated in – Macroscopically intramucosal (cT1a) differentiated carcinomas measuring less than 2cm – There must be no finding of ulceration (scar); UL(–)

• The expanded indications are:

– 1. UL(–) cT1a differentiated carcinomas greater than 2 cm in diameter – 2. UL(+) cT1a differentiated carcinomas less than 3cm in diameter – 3. UL(–) cT1a undifferentiated carcinomas less than 2 cm in diameter. When vascular infiltration (ly, v) is absent together with the above-mentioned criteria, the risk of lymph nodemetastasis is extremely low, and it may be reasonable to expand the indications

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Out of indication lesions? « Staging ER »

• The unreliability of preoperative diagnoses leads to unsatisfactory accurate rate for lesions that are diagnosed as submucosal invasion (pT1b)

• Thus, the indications for treatment are sometimes decided with a view to establishing an accurate histopathological diagnosis “staging or diagnostic ER” – (evidence level V, grade of recommendation C1).

90-95% SM + 80-85% IM

Paris classification

Type 0.I

Type 0.III

Type

0.IIa

0.IIb

0.IIc

Recent data Low risk of LNM in mucosal cancer

• 3951 patients with MGC surgical resection 1994-2010.

• 101 (2.60%) were positive for LNM

• 3/1065 pts (0.3%) who met absolute indication criteria for ESD had LNM

• In expanded indication criteria for ESD, 11/2678 pts (0.4%) had LNM

• Multivariate analysis, revealed the following risk factors for LNM in MGC: – large tumor size

– undifferentiated tumor type

– lymphatic invasion

– perineural invasion

– associated ulceration in the tumor (hazard ratio 1.25, 7.49, 20.65, 23.45, and 4.07, respectively)

Choi K et al. The risk of lymph node metastases in 3951 surgically resected mucosal gastric cancers: implications for endoscopic resection. Gastrointest Endosc. 2015

Prognostic Factors not only linked to M/SM invasion

G3 differentiation

Lymphatic and vascular invasion

Higher risk LNM

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EMR or ESD

• The risk of incomplete resection is high when using EMR for lesions with expanded indications, so ESD should be carried out instead of EMR for these lesions (evidence level V, grade of recommendation C1).

• There have been no randomized controlled trials examining the therapeutic results between EMR and ESD or among EMR or ESD procedures in the stomach. However, a meta-analysis found that, in general, better en bloc resection rates are achieved with ESD than with EMR

Park YM, et al. The effectiveness and safety of ESD compared with EMR for EGC: a systematic review and metaanalysis. Surg. Endosc. 2011; 25: 2666–77.

Recent guidelines

ESGE guidelines Gastric cancer

ESGE Guidelines

• Should be considered for endoscopic resection because of very low risk of LNM: – Noninvasive neoplasia (dysplasia) independently of size – Intramucosal differentiated-type adenocarcinoma, without ulceration

(size≤2cm absolute indication, >2cm expanded indication) – Intramucosal differentiated-type adenocarcinoma, with ulcer, size≤3cm

(expanded indication) – Intramucosal undifferentiated-type adenocarcinoma, size ≤2 cm

(expanded indication) – Differentiated-type adenocarcinoma with superficial submucosal invasion

(sm1,≤500μm), and size≤3cm (expanded indication)

• Several recent studies have shown that clinical outcomes after ESD

were similar for absolute and expanded indication lesions. For this reason it is the ESGE panel’s opinion that ESD should be considered in any lesion with very low possibility of lymph node metastasis

Standard EMR methods

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Polypectomy; Deyhle et al., Endoscopy, 1973

Strip Biopsy; Tada et al., Gastroenterol Endosc, 1984

EMR-C; Inoue et al., Gastrointest Endosc, 1993

EMR-L; Akiyama et al., Gastrointest Endosc, 1997

Soetikno R, Gotoda T, et al. Gastrointest Endosc,2003

Endoscopic resection by standard EMR

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One piece resection Piecemeal resection

Korenaga D, et al. Br J Surg, 2000

Eguchi T, Gotoda T et al. Dig Endosc, 2003

E(M)R cases

Problems with EMR

• If EMR is attempted for lesions > 2 cm, the risk of piecemeal resection might increase, which makes it difficult to determine whether the lateral resection margins are free of disease.

• Previous studies of EMR reported an approximately 75% en bloc resection rate, even for lesions <2 cm

• High risk of local recurrence (2%-35%) with this procedure, especially when EMR cannot achieve en bloc resection

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Ishikawa et al. Gastric Cancer 2007; 10: 35–38.

Local recurrence after standard EMR

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Tanabe et al

Author Methods

Strip Biopsy, EAM 3.5% (15/423)

Recurrence rate

Kawaguchi et al Strip Biopsy, EMR-C 35.3% (97/266)

Ida et al EMR+Laser 6.7% (11/165)

Chonan et al EMR 10.9% (21/193)

Hirao et al ERHSE 2.3% (8/349)

Mitsunaga et al Strip Biopsy 18.2% (54/296)

NCCH (1988-1998) Strip Biopsy 8.5% (53/620)

Tanabe S, et al. Gastrointest Endosc, 2002

Precise histological evaluation Prevention of local recurrence

Importance of En-bloc Resection

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pT1sm1, 72x41 en bloc, R0, Ly-, V-

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ESD CASE

Bleeding control

Increasing speed

Local data Saint-Luc

Total Study period p (test)

2005-2010 (n =41) 2011-2015 (n=57)

Mean lesion size, mm (range) 26 25 (7 - 50) 26 (5 - 60) NS

Mean specimen size, mm (range) 41 40 (15 - 75) 42 (16 - 80) NS

Mean procedure time, min

(range) 104 117 (21 - 208) 94 (20 - 204) 0,035

En bloc resection rate, n (%) 91 (93) 37 (90) 54 (95) NS

R0 resection rate, n (%) 63/98 (64) 20/41 (49) 43/57 (75) 0,006

Standard criteria 19/25 (76) 7/11 (64) 12/14 (86) NS

Expanded criteria 29/36 (81) 8/11 (73) 21/25 (84) NS

Out of criteria 15/37 (41) 5/19 (26) 10/18 (56) NS

3-year disease free survival (%) 77 73 80 NS

3-year overall survival (%) 90 87 93 NS

Belgium, 2015 Portugal, 2014 [24] Germany, 2010 [23]

Case number 109* 136 91

Out of criteria (%) 34 9 13 Undifferenciated/Diffuse (%) 21 2 13 Submucosal carcinoma (%) 25 10 - Ulcer (%) 5 5 5 Mean lesion size (mm) 25 25 -

Median follow-up (months) 47 38 27 Curative resection (%) 86 88 - En bloc resection (%) 94 94 87 Recurrence (%) 8 4 8 Mean time to recurrence (months) 15 9 8

3-year survival rate (%) 90 90 - Mean specimen size (mm) 40 - 41 Mean procedure time (min) 99 85 142

Complications (%) 9 15 14 Bleeding 7 7 8 Perforation 0 0,7 1 Pyloric stenosis 2 0,7 4 Procedure-related death 0 0,7 0

Comparison of Western series

Out of criteria resection

Association of criteria Total (n=37 pts)

pTN (nb of pts

operated)

size>20mm, undifferenciated 6 T1N0 (1)

undifferenciated, sm+ 5 T0N0 (4)

size>20mm, undifferenciated, ulcer 4 T1N1 (2)

size >30mm, sm+ 4 (0)

ulcer, sm+ 3 T0N0 (2), T1N0 (1)

≥sm2 3 (0)

undifferenciated, sm+, lymphatic permeation 2 T0N2 (1)

size>20mm, undifferenciated, sm+ 2 (0)

size>30mm, ulcer, sm+ 2 T0N0 (1)

size>20mm, undifferenciated, ulcer, sm+, lymphatic

permeation 1

(0)

size>30mm, undifferenciated, sm+, lymphatic permeation 1 T1N1 (1)

undifferenciated, ulcer 1 (0)

≥sm2, lymphatic permeation 1 (0)

size>30mm, ulcer 1 (0)

lymphatic permeation 1 T0N0 (1)

Management according to endoscopic resection

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Follow-up

Combined endo-surgical approach

Combined endo-surgical approach/ LECS

Conclusions

• Endoscopic resection (ESD) is recommended for superficial gastric cancer with a low risk of LNM, including expanded indications

• The risk is best assessed on an ESD en block specimen

• Complication rates, including bleeding and perforation, are reaching levels obtained in expert Asian centers

• We observe a trend for higher rates of “out of criteria” lesions (post –ESD restaging) , but some of these patients are too frail for surgery…

Western followers

Japan experts