current status of gastric esd in korea - endotodayendotoday.com/endotoday/20170310.pdf · current...

Current status of gastric ESD in Korea

Jun Haeng Lee. Department of Medicine

Sungkyunkwanuniversity School of Medicie, Seoul, Korea

Contents

• Brief history of gastric ESD in Korea

• ESD/EMR for gastric adenoma

• Pre-treatment diagnostic group

• Indications of ESD in Korea

• Outcomes of ESD for EGC

• Future directions

Brief history of gastric ESD in Korea



Age-adjusted gastric cancer incidence in Korean male

1999 2013 Yearly Change

Stomach 68.4 56.8 -0.8%

Colon 27.0 46.9 5.0%

Lung 51.9 44.9 -0.9%

Liver 48.5 33.7 -2.3%

Thyroid 2.3 28.8 23.4%

Prostate 8.5 26.2 10.5%

National screening program - started in 1999

Stomach cancer

• ≥ 40 years old

• Both males and

females

• Biennial

• Endoscopy or barium

study

Lifetime Screening

Screening by

Recommendation

Stomach 77.9 70.9*

Liver 69.9 21.5

Colon 65.8 44.7

Breast 82.9 70.9

Cervix 77.1 67.9

APJCP 2013;14:6459-6463

*: EGD 63.3%, UGI 36.4%

Kim. APT 2008;27:173-185

0.25% (65/25,536)

The first report on EMR for EGC in Korea

Lee JH. Korean J Gastrointest Endosc 1996;16:928-934

Symposium and live demonstration

2004 Tokyo

2006 Seoul

Early personal experience of gastric ESD (2005)

Clinical pathways of ESD at SMC

Insurance coverage for gastric ESD - But, only conventional indications are covered.

http://thestory.chosun.com/site/data/html_dir/2011/09/06/2011090600596.html

Hands-on training with animal model

SMC 2008

SMC 2016

Development of endoscopic tools

http://www.finemedix.com

ESD knives with water-jet function

http://www.finemedix.com

ESD registry (On-line) - ESD study group, Korean Society of GI Endoscopy

• Started at March 2015

• 26 major ESD centers

• About 7,000 patients enrolled

Current status of ESD for EGC in Korea - From Nov 2011 – Dec 2014

• Number of ESD for EGC cases: 23,828

(2012: 6,664 2013:7,499 2014: 7,734)

• Age: 64.9 +/- 9.9 years (median: 66)

• Male: female = 74.2% : 25.8%

• Hospital stay: 5.0 days

• Medical cost in 2014: 1,510,000 won (1,305 US dollars)

• Surgery within 3 months after ESD: 6.6%

Park CM. 24th KCHUGR Annual Scientific Meeting (2016-12-3)

ESD/EMR for gastric adenoma - A unique feature of endoscopic treatment of gastric neoplasms in Korea



Endoscopic or surgical resection of gastric neoplasms in SMC (2012) - Excluding palliative surgeries

AGC (505)

Beyond absolute indication EGC (949)

Absolute indication EGC (327)

Adenoma with HGD (122)

Adenoma with LGD (141)

EGCs among all gastric cancers: 71.6% (327/1,781) Absolute indication EGCs among all EGCs: 25.6% (327/1,276)

Discrepancy between pre- and post-treatment diagnosis, SMC (2012)

Lee JH. Surg Endosc 2016;30:3987-93

Pathologic diagnosis of gastric dysplasia may be different in two countries.

♠ Korean endoscopists are treating a lot of patients with gastric adenomas, and some of them may be considered as well-differentiated gastric adenocarcinomas in Japan.

Analysis based on the pretreatment diagnostic group



Diagnostic group classifications before and after the treatment

ESD or surgery

LGD HGD AI-EGC EI-EGC BEI-EGC AGC

Pre-treatment diagnostic groups

LGD HGD AI-EGC EI-EGC BEI-EGC AGC

Post-treatment diagnostic groups

Post-treatment analysis of EI-EGCs (2012)

LGD 1

HGD 12

AI-EGC 67

EI-EGC 31

BEI-EGC AGC

ESD 111

LGD HGD AI-EGC EI-EGC 111

BEI-EGC AGC


Pre-treatment analysis of AI-EGCs (2012)

LGD HGD AI-EGC

396 EI-EGC BEI-EGC AGC

ESD 355

LGD 1

HGD 4

AI-EGC 229

EI-EGC 67

BEI-EGC 53

AGC 1


Absolute indication EGC by pre-treatment diagnostic groups

Pre-Tx AI EGC 396

ESD 355

Operation 41

LGD 1

HGD 4

AI EGC 229

AGC 1

LGD 1

BAI EGC 120

AI EGC 29

BAI EGC 11

ESD 1 Surgery 53

Surgery 1 ♠Reason for surgery (multiple) Suspicious lymphadenopathy on CT (18) Multiple lesions (6) Patient’s wish (18) Difficult location (3) Suspicious SM invasion on EUS (2)

* BAI: beyond absolute indications Lee JH. Surg Endosc 2016;30:3987-93

Treatment by pre-Tx diagnostic groups

Treatment

methods

Pre-treatment diagnostic groups

LGD (%)

(n=162)

HGD (%)

(n=164)

Atypical (%)

(n=15)

AI-EGC (%)

(n=396)

BAI-EGC (%)

(n=824)

AGC (%)

(n=495)

ER 160 (95.8) 156 (95.1) 13 (86.7) 297 (75) 42 (5.1) 0

ER + 2nd ER 1 (0.6) 0 0 2 (0.5) 0 0

ER + Op 1 (0.6) 7 (4.3) 2 (13.3) 56 (14.1) 13 (1.6) 0

Operation 0 1 (0.6) 0 41 (10.4) 769 (93.3) 495 (100)

♠ All gastric cancers by pretreatment diagnosis: 1,715 Treatment by endoscopy alone: 341 (19.9%) Treatment by endoscopy + surgery: 69 (4.0%) Treatment by surgery alone: 1,305 (76.1%)


Indications of ESD in Korea



Criteria • Post-treatment

• Additional surgery after ESD

Indication • Pre-treatment

• Selection of ESD candidates

Indications are different from criteria

Indications of ESD in Korea

• ESD candidates are usually selected by the

absolute indications.

• After ESD, expanded criteria is applied to

determine whether the resection was curative.

• There are controversies about the safety of

ESD for expanded indication cases.

Risk of LN metastasis in expanded indication cases

Kang HJ. Gastrointest Endosc 2010;72:508-15

Risk of LN metastasis in mucosal EGC meeting curative resection criteria

Kim YI. Gastric Cancer 2016;19:860-8

Signet ring cell mucosal EGCs - Risk-prediction model

Pyo JH. Ann Surg 2016;264:1038-43

ESD for expanded indication

• Considering the risk of lymph node metastasis,

ESD for expanded indication cases are not

regarded as a standard treatment option, but

selectively performed in the individual cases

basis in Korea.

Outcomes of ESD for EGC



Outcome of endoscopic treatment of EGC with differentiated histology

1. ITT analysis (both curative and non-curative

resection cases)

• Comparison with surgery (propensity score matched

cohort)

2. PP analysis

1) Curative-resection cases: single-arm long-term data

2) Non-curative resection cases: comparison between

surgery group and observation group

Differentiated type EGC

(2002-2012)

(n = 3595)

Excluded

1) LNM on CT or EUS (n=6)

2) Previous gastric cancer (n=20)

3) Cancer of other origin (n=150)

4) Follow up < 2 years (n=856)

EGC meeting indication

treated with curative intent

(n = 2563 )

Endoscopic resection

(n = 1290)

Surgery

(n =1273)


(n = 611 )

Surgery

(n = 611 )

Propensity score

matching

Pyo JH. Am J Gastroenterol 2016

ITT analysis: comparison with surgery - Propensity score matching, differentiated type EGC

Variables

Overall Propensity score matched

Endoscopic

resection

(n=1290)

Surgery

(n=1273) P-value*

Endoscopic

resection

(n=611)

Surgery

(n=611) P -value*

Age, median (IQR), years 61 (54-68) 59 (51-65) <0.001 60 (53-67) 60 (53-67) 0.655

Sex, n(%)

Male

Female

1020 (79.1)

270 (20.9)

947 (74.4)

326 (25.6)

0.005

485 (79.4)

126 (20.6)

487 (79.7)

124 (20.3)

0.885

Performance (ECOG), n(%)

0

1

2 or above

1270 (98.5)

5 (0.4)

15 (1.2)

1261 (99.1)

4 (0.3)

8 (0.6)

0.339

605 (99.0)

1 (0.2)

5 (0.8)

604 (98.9)

2 (0.0)

5 (0.8)

0.847

F/U duration, median (IQR), month 44 (32-60) 58 (38-72) <0.001 46 (32-61) 58 (38-73) 0.066

Criteria of indication, n(%)

Absolute criterion

Expanded criterion I

Expanded criterion II

Expanded criterion III

Beyond indication

895 (69.4)

178 (13.8)

7 (0.5)

100 (7.8)

110 (8.5)

536 (42.1)

460 (36.1)

36 (2.8)

130 (10.2)

111 (8.7)

<0.001

386 (63.2)

127 (20.8)

5 (0.8)

44 (7.2)

49 (8.0)

362 (59.2)

123 (20.1)

16 (2.6)

84 (13.7)

26 (4.3)

<0.001


ITT analysis: comparison with surgery - Baseline characteristics (1)

ITT analysis: comparison with surgery - Baseline characteristics (2)

Variables

Overall Propensity score matched

Endoscopic

resection

(n=1290)

Surgery

(n=1273) P-value*

Endoscopic

resection

(n=611)

Surgery

(n=611) P -value*

Tumor size, mean (SD), cm 1.4 (0.9) 2.6 (1.7) <0.001 1.7 (1.1) 1.7 (1.1) 0.021

Morphology of tumor, n(%)

Elevated

Flat or depressed

770 (59.7)

520 (40.3)

192 (15.1)

1081 (84.9)

<0.001

131 (21.4)

480 (78.6)

140 (22.9)

471 (77.1)

0.384

Location of tumor, n(%)

Upper third

Middle third

Lower third

78 (6.1)

357 (27.7)

855 (66.3)

89 (7.0)

331 (26.0)

853 (67.0)

0.450

40 (6.6)

180 (29.5)

391 (64.0)

45 (7.4)

170 (27.8)

396 (64.8)

0.721

Histology of tumor, n(%)

Well differentiated

Moderately differentiated

511 (39.6)

779 (60.4)

429 (33.7)

844 (66.3)

0.002

229 (37.5)

382 (62.5)

224 (36.7)

387 (63.3)

0.770

Depth of tumor invasion, n(%)

Mucosa

Submucosa

1076 (83.4)

214 (16.6)

1054 (82.8)

219 (17.2)

0.678

515 (84.3)

96 (15.7)

504 (82.5)

107 (17.5)

0.377

Lymphovascular invasion

Absent

Present

1217 (94.3)

73 (5.7)

1226 (96.3)

47 (3.7)

0.018

577(94.4)

34 (5.6)

588 (96.2)

23 (3.8)

0.124

R0 resection

No

Yes

223 (17.3)

1067 (82.7)

46 (3.6)

1227 (96.4)

<0.001

109 (17.8)

502 (82.2)

23 (3.8)

588 (96.2)

<0.001



Surgery

Overall survival

Disease specific survival Recurrence free survival

Disease free survival


PP analysis (1): single-arm follow-up - Differentiated, curative (n=1,306)

• EGCs treated by ESD at Samsung Medical Center

• 1,838 patients with 1,889 differentiated-type EGCs

• November 2003 – May 2011

• Censoring date: May 2014

• Differentiated-type EGC

– Well or moderately differentiated or papillary EGC

– According to the quantitatively predominant histologic type

– Differentiated-type EGC > 50%

Min BH. Endoscopy 2015

PP analysis (1): single-arm follow-up - Differentiated, curative (n=1,306)

• Median follow-up: 61 months (range 17-122)

• Local recurrence: 0.08% (1/1,306)

• Metachronous recurrence: 3.6% (47/1,306)

– Definition of metachronous recurrence: at least 12 months after ER

• Extragastric recurrence: 0.15% (2/1,306)

• 5-year overall survival

– Absolute indication: 97.3%

– Expanded indication: 96.4%


Overall-survival - 1,306 curative ESDs from December 2003 to May 2011


Two extragastric recurrences (0.15%)


Extragastric recurrence after curative endoscopic resection in Korea

Rate of extragastric recurrence

Reference

Samsung Medical Center

0.15% (2/1,306) Min BH. Endoscopy 2015

Asan Medical Center 0.14% (5/3,588) Lee S. Gastric Cancer 2017

Severance Hospital 0.15% (2/1347) Hahn KY. Gastrointest Endosc 2016

Seoul National University

0.50% (2/404) Choi KS. Radiology 2016

Noncurative resection

341

Lateral margin positive

67 (19.6%)

Risk of lymph node metastasis

274 (80.4%)

Surgery

194 (70.8%)

Observation

80 (29.2%) • Patients’ refusal : 64 • High surgical risk : 8

(severe comorbidities) • Concomitant

advanced cancer in other organs : 8

Lymph node 11 (5.6%)

Local residual 10 (5.2%)

PP analysis (2): non-curative resection - Comparison between surgery and observation group

Kim ER. Br J Surg 2015

Predictors of LN metastasis (5.7%)


Progression into advanced cancer

5 cases (6.3%) (21 to 40 months)

1 case (0.5%) (22 months)

Observation group Surgery group

(P = 0.013)


Overall survival - Median duration of follow-up after ER: 60.5 months (6-141)


Survival benefit of additional surgery - Additional surgery: 127, follow-up: 67

Observation group Additional surgery group

Eom BW. Gastrointest Endosc 2017;85:155-63

Future directions - Non-exposure full thickness resection - Insights from genetic studies



Simple non-exposure EFTR

• 1st step: Laparoscopic seromuscular suturing, which resulted in inversion

of the stomach wall (the suture material for this had evenly spaced

unidirectional barbs, which eliminated the need to tie a knot; V-Loc 180

3-0, Covidien, Mansfield, MA, USA).

• 2nd step: EFTR of the inverted stomach wall from inside the stomach with

a conventional needle knife

• 3rd step: Endoscopic mucosal suturing with endoloops and clips.

Endoscopy 2015;47:1171-4 Courtesy of Kim CG (NCC, Korea).

Randomized comparative animal study

Courtesy of Kim CG (NCC, Korea). Presented in Korean DDW 2015


Courtesy of Kim CG (NCC, Korea).

Stapler group

EFTR group

Presented in Korean DDW 2015



Stapler group EFTR group P-value

Success of closure 100% (8/8) 100% (8/8) 0.999

Complete resection 75% (2/8) 100% (8/8) 0.467

Complication 25% (2/8) 0% (8/8) 0.467

Leakage 13%(1/8)* 0% (0/8)

Stenosis 13%(1/8)† 0% (0/8)

*Gastric cardia, † Angle-antrumAW




Stapler group (mean±SD, cm)

EFTR group (mean±SD, cm)

P-value

Imaginary EGC

Length 2.3±0.4 2.4±0.3 0.499

Circumference 6.3±0.7 6.7±0.9 0.617

Resected specimen

Length 8.0±0.8 4.4±0.5 <0.001

Circumference 21.0±2.7 12.5±1.0 <0.001

Procedure time (mean±SD) 31.7± 10.0 118.1±23.4 <0.001

The size of resected tissue was significantly smaller in EFTR group (P<0.001)

The procedure time were significantly longer in EFTR group (mean±SD;

(112.3±27.4 min) than linear stapler group, 29.5±12.7 min p<0.001)


Genetic changes in early gastric carcinogenesis

• Min et al. investigated the genomic and

transcriptomic landscape of adenoma with LGD,

adenoma with HGD, and EGC.

• Several genetic changes have been identified

in advanced gastric cancer, but the genetic

alterations associated with early gastric

carcinogenesis remain unclear.

Min BH. J Pathol 2016;240:304-314

Genetic changes in early gastric carcinogenesis

Min BH. J Pathol 2016;240:304-314

He found that the expression pattern clearly divided into normal, LGD, and EGC, whereas those of HGD overlapped with LGD or EGC. RNF 43 mutation were present only in HGD and EGC.

Adenoma-carcinoma model of gastric multistep carcinogenesis

Min BH. J Pathol 2016;240:304-314

Take home message

• ESD is widely performed for EGCs in the absolute

indication in Korea. Annually, its more than 7,000

cases.

• We are still very careful about expanded indication

cases. It’s done usually for flat SRCs less than 1 cm.

• Strategies for non-curative resection cases are still

under investigation.

Thank you for your attention.

Current status of ESD for EGC in Korea - From Nov 2011 – Dec 2014

• Number of ESD for EGC cases: 23,828

(2012: 6,664 2013:7,499 2014: 7,734)

• Age: 64.9 +/- 9.9 years (median: 66)

• Male: female = 74.2% : 25.8%

• Hospital stay: 5.0 days

• Medical cost in 2014: 1,510,000 won (1,305 US dollars)

• Surgery within 3 months after ESD: 6.6%

Park CM. 24th KCHUGR Annual Scientific Meeting (2016-12-3)

current status of gastric esd in korea - endotodayendotoday.com/endotoday/20170310.pdf · current...

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