( 三 ) Present and Future Perspectives of Endoscopic Diagnosis and Treatment for Early Gastric Cancer

外賓演講（三）

PRESENT AND FUTURE PERSPECTIVES OF ENDOSCOPIC DIAGNOSIS AND TREATMENT FOR EARLY GASTRIC CANCER

Mitsuhiro Fujishiro The University of Tokyo, Japen

Gastric cancers are still one of the major causes of cancer death worldwide. Although the situation is the same in Japan, age-adjusted incidence and mortality of gastric cancer are consistently decreasing year by year in Japan. These trends mainly depend on the decrease of Helicobacter pylori (HP) infected patients, mass-screening of gastric cancer, and wide spread use of upper GI endoscopy.

In terms of endoscopic diagnosis of early gastric cancers, white light image (WLI) is still the gold standard for detection of gastric cancer and optical digital method such as NBI, BLI, and OE with the combined use of magnifying endoscope is now widely used for characterization of gastric cancer. Magnifying endoscopy simple diagnostic algorithm for early gastric cancer (MESDA-G) was established in cooperation with the Japanese Gastroenterological Association, Japan Gastroenterological Endoscopy Society, and the Japanese Gastric Cancer Association (Muto M, et al. Dig Endosc. 2016;28:379-93). If we detect a suspicious lesion, identification of a demarcation line (DL) between the lesion and the background mucosa is the first step in distinguishing gastric cancer from a noncancerous lesion. If a DL is absent, the diagnosis of a benign lesion may be made. If a DL is present, the subsequent presence of an irregular microvascular (MV) pattern and an irregular microsurface (MS) pattern should be determined. If irregular MV and/or MS patterns are present within the demarcation line, the diagnosis of gastric cancer can be made. Furthermore, in terms of MV pattern, majority of differentiated type cancers show fine network pattern and majority of undifferentiated type cancers show corkscrew pattern or wavy microvessels, which is useful to predict histological type of early gastric cancer. Recently, endocytoscope (ECS) is commercially available, which enables us to make the target lesions as no, mild and severe atypia in cells and structures (Kaise M, et al. Endoscopy 2014; 46: 827–832). Additionally, artificial intelligence is also in progress for diagnosis of early gastric cancer (Hirasawa T, et al. Gastric Cancer. 2018; 21:653-660).

Strategy of endoscopic treatment of early gastric cancers is based on the guidelines endoscopic submucosal dissection and endoscopic mucosal resection for early gastric cancer (second edition) (Ono H, et al. Dig Endosc. 2021;33:4-20) and Japanese gastric cancer treatment guidelines 2021 (6th edition). Based on the open data No.4 by National Database in Japan, 54,742 cases of gastric cancers are treated by endoscopic resection in Japan, which accounts for 41% of the total gastric cancers. Majority of the cancers are treated by ESD, which is a method whereby the mucosa surrounding the lesion is excised using a high-frequency diathermy device, followed by dissection of the submucosa beneath the lesion. By using ESD, technical hurdles have been nearly overcome in terms of size, location, fibrosis, and morphology of the lesions.

Endoscopic resection, either EMR or ESD, is absolutely indicated in ‘clinically intramucosal (cT1a) differentiated carcinomas measuring less than 2cm in diameter. The macroscopic type does not matter, but there must be no finding of ulceration (scar);

i.e. UL(–).’ The absolute indications for ESD are: ‘1. UL(–) cT1a differentiated carcinomas greater than 2cm in diameter; 2. UL(+) cT1a differentiated carcinomas less than 3cm in diameter; and 3. UL(–) cT1a undifferentiated carcinomas less than 2 cm in diameter.’ If a lesion falls within the indication criteria at the initial ESD or EMR, subsequent locally recurrent intramucosal cancers may be dealt with under expanded indications of ESD.

Several cutting devices are commercially available for ESD, but each of them has merits and demerits. It is important to use appropriate devices for appropriate situations in consideration with personal experiences and preferences. Recently, traction method by using “clip with line” is widely used for safer and faster ESD. Major complications are bleeding and perforation. BEST-J score (Bleeding after gastric ESD Trend from Japan) is available for stratification of risks of post-operative bleeding (Hatta W, et al. Gut. 2021;70:476-484).

When the lesion is resected en bloc, the following conditions: (i) predominantly differentiated type, pT1a, UL0, HM0 VM0, Ly0, V0, regardless of size; (ii) long diameter ≤2 cm, predominantly undifferentiated type, pT1a, UL0, HM0, VM0, Ly0, V0; or (iii) long diameter ≤3 cm, predominantly differentiated type, pT1a, UL1, HM0, VM0, Ly0, V0, are considered for endoscopic curability A (eCuraA). When the lesion is resected en bloc, is ≤3 cm in long diameter, predominantly of the differentiated type, and satisfies the following criteria: pT1b1(SM1) (within <500 μm from the muscularis mucosae), HM0, VM0, Ly0, and V0, it is considered endoscopic curability B (eCuraB).

When a lesion meets neither of the abovementioned eCuraA and B conditions, it is considered eCuraC, which has a likelihood of remnant tumor. When eCuraC lesions are differentiated-type lesions and fulfill other criteria to be classified into either eCuraA or eCuraB but was either not resected en bloc or had positive HM, they are considered eCuraC-1. All other eCuraC lesions are considered eCuraC-2.

The risk of metastasis is low in eCuraC-1 lesions. In addition to surgical resection, repeat ESD, diathermy, and follow-up without treatment are possible options, with the patient’s informed consent, according to the policy of the treating institution.

In light of the fact that Japanese population is ageing, strict criteria for node negative cancers are not the only guides to perform additional surgery after endoscopic resection. We may follow the patients without it due to their comorbidities and wishes after thorough explanation of probability of lymph node metastases. In this point, eCura system is very useful to predict the risk of lymph node metastases from the pathological evaluation of the endoscopically resected specimens. In eCura system, five risk factors for LNM were weighted with point values: three points for lymphatic invasion and 1 point each for tumor size >30mm, positive vertical margin, venous invasion, and submucosal invasion ≥500μm. Accordingly, the patients were categorized into three LNM risk groups: low (0-1 point: 2.5% risk), intermediate (2-4 points: 6.7%), and high (5-7 points: 22.7%) (Hatta W et al. Am J Gastroenterol. 2017;112:874-881).

As the novel full thickness resection, laparoscopy and endoscopy cooperative surgery (LECS) was innovated. One of the promising LECS techniques is non-exposed endoscopic wall-inversion Surgery (NEWS), which is applicable node-negative early gastric cancer (Fujishiro M, et al. Nagoya J Med Sci. 2020;82:175-182). The combination of NEWS and sentinel node biopsy is expected to be a minimally invasive, function-preserving surgery that may replace radical gastrectomy as the next agenda.