Is the West finally reaching the East in endoscopic submucosal dissection? The gastric cancer case

Endoscopic mucosal resection is currently indicated for differentiated type gastric adenocarcinomas, without ulcerative findings, that are ≤ 2 cm in size and estimated to be limited to the mucosa (T1a). The resection is curative if the lesion is resected “en bloc,” the margins are free of disease (R0), there is no lymphovascular invasion, and the lesion is limited to the mucosa (T1a). These are the Japanese “guideline criteria” that were revised in 2014 [1].

“Is the West finally reaching the East in gastric ESD? The answer is probably yes, but slowly, and only in high-volume centers.”

Endoscopic submucosal dissection (ESD) is recommended for early adenocarcinomas that are outside the guideline criteria – the “expanded indication criteria.” Differentiated lesions > 2 cm or ulcerated differentiated lesions ≤ 3 cm or ulcerated undifferentiated lesions ≤ 2 cm may be treated if they are estimated to be limited to the mucosa (T1a). In addition to the previous guideline curative criteria, ESD of expanded criteria lesions is also curative for differentiated lesions ≤ 3 cm with less than 500 µm submucosal invasion (T1b). The expanded criteria were considered to be investigational until the results of the JCOG0607 trial were recently published [2]. A total of 470 early gastric cancer lesions matching the expanded criteria were curatively treated by ESD in 29 Japanese centers between June 2007 and October 2010. The rate of curative resection was 67.4 % (317 lesions) and there were no recurrences for these patients. There were no deaths due to gastric cancer in the curative resection group, and the 5-year overall survival was 97.0 %. ESD instead of surgery is now recommended by the Japanese Gastric Cancer Association for expanded criteria lesions.

Similar recommendations were made by the European Society of Gastrointestinal Endoscopy (ESGE) [3].

In this issue of Endoscopy, Probst et al. report the results of the largest series to date on ESD for early gastric cancer in the Western world [4]. A total of 191 early gastric cancers were treated by ESD between January 2005 and September 2016. After ESD, the majority of the lesions met the expanded criteria (48.6 %), 29.6 % met guideline criteria, and 21.8 % were out of the indications. Although only 73.6 % of expanded criteria lesions were curatively resected compared with 90.2 % of guideline criteria lesions (P = 0.02), there was no difference in survival between the two groups (P = 0.58) and there was no gastric cancer-related mortality in either group. The authors compared their results favorably with the previous Japanese ESD series in terms of efficacy and safety.

As Western authors are comparing their work on ESD with their Eastern colleagues, one cannot help but wonder about the conditions that have led to ESD being developed and performed mainly in the East …

The most important factor may be the high number of lesions available for treatment in the East. The incidence of gastric cancer is higher in Asia, there are implemented screening programs for gastric cancer [5] and endoscopists may systematically take a longer time to examine the gastric mucosa.

Probst et al. included 91 expanded criteria lesions in 141 months in a single center (approximatively one expanded criteria lesion every 2 months per center, two endoscopists), while the JCOG0607 trial included 470 expanded criteria lesions in 40 months in 29 centers (approximatively one expanded criteria lesion every 2.5 months per center). Remarkably, the inclusion rate of expanded criteria lesions per center was quite similar. The Japanese trial included more patients in a shorter time only because there were 29 centers.

Comparatively, Western reports of ESD for early gastric cancer include either large national single centers (e. g. Pimentel Nunes in Portugal [6] and Repici in Italy [7]) or multicentric reports on all ESD-treated lesions (e. g. Barret in France [8]). A total of 42 expanded criteria early gastric cancers were included in 122 months in Portugal (one expanded criteria lesion every 3 months, single center, 2 endoscopists), 10 early gastric cancers in 49 months in Italy (number of expanded criteria lesions unknown, one lesion every 5 months, single center, 1 endoscopist), and 104 neoplastic gastric lesions in 36 months in France (number of early gastric cancers and specifically expanded criteria lesions unknown, one lesion every 3 months, 14 centers, 20 endoscopists, but 80 % of lesions in 4 centers only).

So, a high number of available early gastric cancers in the East has led to the development of many centers conducting a high volume of ESD procedures, while in the West, the limited availability of lesions has led to very few high-volume centers eventually approaching the Eastern inclusion rates and some very low-volume centers.

Another limiting factor for ESD development in the West is the unfavorable shape of the learning curve. The learning process takes time, as the Probst team noted: their R0 resection rate significantly increased in the second part of the study (59.4 % to 92.6 %; P < 0.001) and there was a significant decrease in procedure time (148 to 110 minutes; P < 0.001). This is why many Western experts in ESD train in Japan for a certain period of time before implementing the procedure at home [6] [8]. It is important to note that in the JCOG0607 trial, participating experts were required to have an experience of at least 100 ESD procedures.

When the availability of the lesions is high, the number of treated patients in the West increases. For example, per-oral endoscopic myotomy (POEM) for achalasia was introduced in Japan in 2010 by Inoue [9]. Since then, it has spread in the Western world, and the number of Western patients with achalasia treated by POEM in the past 7 years has largely surpassed the number of Western patients with early gastric cancer treated by ESD in the past 18 years.

Other potential causes for ESD development in the East are: improved endoscopic instrument handling by endoscopists (some have argued that using chopsticks regularly may lead to this [10]); ESD is often performed in unsedated or lightly sedated patients (making it easier to change the patient’s position if needed); surgeons perform ESD and have less fear of complications (Professor Haruhiro Inoue is a thoracic surgeon); there are separate training pathways for upper and lower ESD; and there may be a closer relationship with the research and development units of companies that manufacture endoscopy instrumentation.

Are we finally reaching the East in ESD? The answer is probably yes, but slowly, and only in high-volume centers.

• References

• 1 Japanese Gastric Cancer Association. Japanese gastric cancer treatment guidelines 2014 (ver. 4). Gastric Cancer 2017; 20: 1-19
• 2 Hasuike N, Ono H, Boku N. et al. Gastrointestinal Endoscopy Group of Japan Clinical Oncology Group (JCOG-GIESG). A non-randomized confirmatory trial of an expanded indication for endoscopic submucosal dissection for intestinal-type gastric cancer (cT1a): the Japan Clinical Oncology Group study (JCOG0607). Gastric Cancer 2017; DOI: 10.1007/s10120-017-0704-y.
• 3 Pimentel-Nunes P, Dinis-Ribeiro M, Ponchon T. et al. Endoscopic submucosal dissection: European Society of Gastrointestinal Endoscopy (ESGE) Guideline. Endoscopy 2015; 47: 829-854
• 4 Probst A, Schneider A, Schaller T. et al. Endoscopic submucosal dissection for early gastric cancer: are expanded resection criteria safe for Western patients?. Endoscopy 2017; 49: 855-865
• 5 Hamashima C, Shibuya D, Yamazaki H. et al. The Japanese guidelines for gastric cancer screening. Jpn J Clin Oncol 2008; 38: 259-267
• 6 Pimentel-Nunes P, Mourao F, Veloso N. et al. Long-term follow-up after endoscopic resection of gastric superficial neoplastic lesions in Portugal. Endoscopy 2014; 46: 933-940
• 7 Repici A, Zullo A, Hassan C. et al. Endoscopic submucosal dissection of early gastric neoplastic lesions. Eur J Gastroenterol Hepatol 2013; 25: 1261-1265
• 8 Barret M, Lepilliez V, Coumaros D. et al. The expansion of endoscopic submucosal dissection in France: a prospective nationwide survey. United European Gastroenterol J 2017; 5: 45-53
• 9 Inoue H, Minami H, Kobayashi Y. et al. Peroral endoscopic myotomy (POEM) for esophageal achalasia. Endoscopy 2010; 42: 265-271
• 10 Kimura T. Endoscopic surgery: current status in Japan. JMAJ 2009; 52: 325-329