Current status of gastric ESD in Korea. Jun Haeng Lee. Department of Medicine Sungkyunkwanuniversity School of Medicie, Seoul, Korea

Transcription

1 Current status of gastric ESD in Korea Jun Haeng Lee. Department of Medicine Sungkyunkwanuniversity School of Medicie, Seoul, Korea

2 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

3 Brief history of gastric ESD in Korea Jun Haeng Lee. Department of Medicine Sungkyunkwanuniversity School of Medicie, Seoul, Korea

4 Age-adjusted gastric cancer incidence in Korean male Yearly Change Stomach % Colon % Lung % Liver % Thyroid % Prostate %

5 National screening program - started in 1999 Stomach cancer 40 years old Lifetime Screening Screening by Recommendation Both males and females Biennial Endoscopy or barium study Stomach * Liver Colon Breast Cervix *: EGD 63.3%, UGI 36.4% APJCP 2013;14:

6 0.25% (65/25,536) Kim. APT 2008;27:

7 The first report on EMR for EGC in Korea Lee JH. Korean J Gastrointest Endosc 1996;16:

8 Symposium and live demonstration 2004 Tokyo 2006 Seoul

9 Early personal experience of gastric ESD (2005)

10 Clinical pathways of ESD at SMC

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

12 Hands-on training with animal model SMC 2008 SMC 2016

13 Development of endoscopic tools

14 ESD knives with water-jet function

15 ESD registry (On-line) - ESD study group, Korean Society of GI Endoscopy Started at March major ESD centers About 7,000 patients enrolled

16 Current status of ESD for EGC in Korea - From Nov 2011 Dec 2014 Number of ESD for EGC cases: 23,828 (2012: 6, :7, : 7,734) Age: /- 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. 24 th KCHUGR Annual Scientific Meeting ( )

17 ESD/EMR for gastric adenoma - A unique feature of endoscopic treatment of gastric neoplasms in Korea Jun Haeng Lee. Department of Medicine Sungkyunkwanuniversity School of Medicie, Seoul, Korea

18 Endoscopic or surgical resection of gastric neoplasms in SMC (2012) - Excluding palliative surgeries Adenoma with LGD (141) Adenoma with HGD (122) Absolute indication EGC (327) AGC (505) Beyond absolute indication EGC (949) EGCs among all gastric cancers: 71.6% (327/1,781) Absolute indication EGCs among all EGCs: 25.6% (327/1,276)

19 Discrepancy between pre- and posttreatment diagnosis, SMC (2012) Lee JH. Surg Endosc 2016;30:

20 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.

21 Analysis based on the pretreatment diagnostic group Jun Haeng Lee. Department of Medicine Sungkyunkwanuniversity School of Medicie, Seoul, Korea

22 Diagnostic group classifications before and after the treatment Pre-treatment diagnostic groups LGD HGD AI-EGC EI-EGC BEI-EGC AGC ESD or surgery Post-treatment diagnostic groups LGD HGD AI-EGC EI-EGC BEI-EGC AGC

23 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 Lee JH. Surg Endosc 2016;30:

24 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 Lee JH. Surg Endosc 2016;30:

25 Absolute indication EGC by pre-treatment diagnostic groups Pre-Tx AI EGC 396 ESD 355 Operation 41 LGD 1 HGD 4 AI EGC 229 BAI EGC 120 AGC 1 LGD 1 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:

26 Treatment by pre-tx diagnostic groups Pre-treatment diagnostic groups Treatment methods LGD (%) HGD (%) Atypical (%) AI-EGC (%) BAI-EGC (%) AGC (%) (n=162) (n=164) (n=15) (n=396) (n=824) (n=495) ER 160 (95.8) 156 (95.1) 13 (86.7) 297 (75) 42 (5.1) 0 ER + 2 nd ER 1 (0.6) (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%) Lee JH. Surg Endosc 2016;30:

27 Indications of ESD in Korea Jun Haeng Lee. Department of Medicine Sungkyunkwanuniversity School of Medicie, Seoul, Korea

28 Indications are different from criteria Indication Pre-treatment Selection of ESD candidates Criteria Post-treatment Additional surgery after ESD

29 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.

30 Risk of LN metastasis in expanded indication cases Kang HJ. Gastrointest Endosc 2010;72:508-15

31 Risk of LN metastasis in mucosal EGC meeting curative resection criteria Kim YI. Gastric Cancer 2016;19:860-8

32 Signet ring cell mucosal EGCs - Risk-prediction model Pyo JH. Ann Surg 2016;264:

33 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.

34 Outcomes of ESD for EGC Jun Haeng Lee. Department of Medicine Sungkyunkwanuniversity School of Medicie, Seoul, Korea

35 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

36 ITT analysis: comparison with surgery - Propensity score matching, differentiated type EGC Differentiated type EGC ( ) (n = 3595) EGC meeting indication treated with curative intent (n = 2563 ) 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) Endoscopic resection (n = 1290) Surgery (n =1273) Propensity score matching Endoscopic resection (n = 611 ) Surgery (n = 611 ) Pyo JH. Am J Gastroenterol 2016

37 ITT analysis: comparison with surgery - Baseline characteristics (1) Overall Propensity score matched Variables 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) < (53-67) 60 (53-67) Sex, n(%) Male Female 1020 (79.1) 270 (20.9) 947 (74.4) 326 (25.6) (79.4) 126 (20.6) 487 (79.7) 124 (20.3) Performance (ECOG), n(%) or above 1270 (98.5) 5 (0.4) 15 (1.2) 1261 (99.1) 4 (0.3) 8 (0.6) (99.0) 1 (0.2) 5 (0.8) 604 (98.9) 2 (0.0) 5 (0.8) F/U duration, median (IQR), month 44 (32-60) 58 (38-72) < (32-61) 58 (38-73) 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) < (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 Pyo JH. Am J Gastroenterol 2016

38 ITT analysis: comparison with surgery - Baseline characteristics (2) Variables Endoscopic resection (n=1290) Overall Surgery (n=1273) P-value* Propensity score matched Endoscopic resection (n=611) Surgery (n=611) P -value* Tumor size, mean (SD), cm 1.4 (0.9) 2.6 (1.7) < (1.1) 1.7 (1.1) Morphology of tumor, n(%) Elevated Flat or depressed 770 (59.7) 520 (40.3) 192 (15.1) 1081 (84.9) < (21.4) 480 (78.6) 140 (22.9) 471 (77.1) Location of tumor, n(%) Upper third Middle third Lower third Histology of tumor, n(%) Well differentiated Moderately differentiated Depth of tumor invasion, n(%) Mucosa Submucosa Lymphovascular invasion Absent Present R0 resection No Yes 78 (6.1) 357 (27.7) 855 (66.3) 511 (39.6) 779 (60.4) 1076 (83.4) 214 (16.6) 1217 (94.3) 73 (5.7) 223 (17.3) 1067 (82.7) 89 (7.0) 331 (26.0) 853 (67.0) 429 (33.7) 844 (66.3) 1054 (82.8) 219 (17.2) 1226 (96.3) 47 (3.7) 46 (3.6) 1227 (96.4) (6.6) 180 (29.5) 391 (64.0) (37.5) 382 (62.5) (84.3) 96 (15.7) (94.4) 34 (5.6) < (17.8) 502 (82.2) 45 (7.4) 170 (27.8) 396 (64.8) 224 (36.7) 387 (63.3) 504 (82.5) 107 (17.5) 588 (96.2) 23 (3.8) 23 (3.8) 588 (96.2) <0.001 Pyo JH. Am J Gastroenterol 2016

39 Overall survival Disease free survival Endoscopic resection Surgery Disease specific survival Recurrence free survival Pyo JH. Am J Gastroenterol 2016

40 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

41 PP analysis (1): single-arm follow-up - Differentiated, curative (n=1,306) Median follow-up: 61 months (range ) 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% Min BH. Endoscopy 2015

42 Overall-survival - 1,306 curative ESDs from December 2003 to May 2011 Min BH. Endoscopy 2015

43 Two extragastric recurrences (0.15%) Min BH. Endoscopy 2015

44 Extragastric recurrence after curative endoscopic resection in Korea Samsung Medical Center Rate of extragastric recurrence 0.15% (2/1,306) Reference Min BH. Endoscopy 2015 Asan Medical Center 0.14% (5/3,588) Lee S. Gastric Cancer 2017 Severance Hospital 0.15% (2/1347) Seoul National University Hahn KY. Gastrointest Endosc % (2/404) Choi KS. Radiology 2016

45 PP analysis (2): non-curative resection - Comparison between surgery and observation group Noncurative resection 341 Lateral margin positive 67 (19.6%) Risk of lymph node metastasis 274 (80.4%) Surgery 194 (70.8%) Lymph node 11 (5.6%) Local residual 10 (5.2%) Observation 80 (29.2%) Patients refusal : 64 High surgical risk : 8 (severe comorbidities) Concomitant advanced cancer in other organs : 8 Kim ER. Br J Surg 2015

46 Predictors of LN metastasis (5.7%) Kim ER. Br J Surg 2015

47 Progression into advanced cancer Observation group Surgery group 5 cases (6.3%) (21 to 40 months) 1 case (0.5%) (22 months) (P = 0.013) Kim ER. Br J Surg 2015

48 Overall survival - Median duration of follow-up after ER: 60.5 months (6-141) Kim ER. Br J Surg 2015

49 Survival benefit of additional surgery - Additional surgery: 127, follow-up: 67 Additional surgery group Observation group Eom BW. Gastrointest Endosc 2017;85:155-63

50 Future directions - Non-exposure full thickness resection - Insights from genetic studies Jun Haeng Lee. Department of Medicine Sungkyunkwanuniversity School of Medicie, Seoul, Korea

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

52 Randomized comparative animal study Courtesy of Kim CG (NCC, Korea). Presented in Korean DDW 2015

53 Randomized comparative animal study Stapler group EFTR group Courtesy of Kim CG (NCC, Korea). Presented in Korean DDW 2015

54 Randomized comparative animal study Stapler group EFTR group P-value Success of closure 100% (8/8) 100% (8/8) Complete resection 75% (2/8) 100% (8/8) Complication 25% (2/8) 0% (8/8) Leakage 13%(1/8)* 0% (0/8) Stenosis 13%(1/8) 0% (0/8) *Gastric cardia, Angle-antrumAW Courtesy of Kim CG (NCC, Korea). Presented in Korean DDW 2015

55 Randomized comparative animal study Stapler group (mean±sd, cm) EFTR group (mean±sd, cm) P-value Imaginary EGC Length 2.3± ± Circumference 6.3± ± Resected specimen Length 8.0± ±0.5 <0.001 Circumference 21.0± ±1.0 <0.001 Procedure time (mean±sd) 31.7± ±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) Courtesy of Kim CG (NCC, Korea). Presented in Korean DDW 2015

56 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:

57 Genetic changes in early gastric carcinogenesis 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. Min BH. J Pathol 2016;240:

58 Adenoma-carcinoma model of gastric multistep carcinogenesis Min BH. J Pathol 2016;240:

59 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.

60 Thank you for your attention.

61 Current status of ESD for EGC in Korea - From Nov 2011 Dec 2014 Number of ESD for EGC cases: 23,828 (2012: 6, :7, : 7,734) Age: /- 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. 24 th KCHUGR Annual Scientific Meeting ( )