Patients and methods

A prospective analysis of 479 EGCs in 445 patients resected by EMR at NCCH, Tokyo, from March 1987 to December 1998 was performed. These were 413 solitary, 17 double, one triple, one quadruple, and 13 metachronous tumours.

Mean age of the patients was 67.6 years (range 34–92), the male to female ratio was 4.13 (357/88), and the follow up period was 3–125 months (median 45 months).

The Japanese Classification of Gastric Carcinoma was used for tumour description.1 The indications for EMR are determined by the risk of lymph node metastasis5 and such technical considerations as the size and position of the lesion, and the equipment and expertise available locally. Current indications for EMR at the NCCH are shown in table 1. When EMR was introduced to the NCCH in 1987, the indication size was 15 mm or less in diameter, and multifragment resection was not accepted. However, it was increased to 30 mm because multifragment resection was introduced based on a review of resected cancers and the development of appropriate endoscopic techniques.

As it is sometimes difficult to accurately assess the depth of invasion prior to EMR,7 we are prepared to remove any lesion that appears to be confined to the mucosa if it meets the other criteria.

In this series, most EMRs were performed by the so called “strip biopsy method”, a relatively simple technique that has been described elsewhere.6 ,8 Since 1997, a new EMR procedure using an insulation tipped diathermic knife (IT knife) was used in the majority of cases9 (fig 1).

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Figure 1

Endoscopic mucosal resection procedure using an IT knife. (A) Superficial elevated (IIa type) early gastric cancer (EGC) located on the lesser curvature of the lower body after spraying with indigo carmine dye. (B) Marking dots were made using a precut knife on the circumference of the target lesion to clarify the margin. (C) After injection of saline with epinephrine (0.025 mg/ml) into the submucosal layer, an initial cut was made with a conventional needle knife outside of the dots. The IT knife was inserted into this cut and operated to cut around the lesion. (D) The tumour marked by dots was separated from the surrounding normal mucosa. (E) The tumour was removed by standard polypectomy with a combination of cutting and coagulation current in a single fragment. (F) The resected specimen showed well differentiated adenocarcinoma (20×25 mm) with a clear lateral margin. (G) The specifications of the insulation tipped diathermic knife, which was developed by Dr Hosokawa in 1994. The knife consists of a conventional diathermic needle knife (KD-1L; Olympus, Japan) with a ceramic ball at the top to minimise the risk of perforation.

Follow up endoscopy was performed at three and six months after EMR in the first year, and yearly thereafter to diagnose local recurrence.

Results

EVALUATION OF RESECTED SPECIMENS

The macroscopic appearances of the resected tumours are summarized in table 3. A total of 429 lesions (90%) were less than 20 mm in diameter while 280 lesions (58%) were of the superficial depressed type (0-IIc type). The tumours were located in the upper third (82 lesions, 17%), middle third (166 lesions, 35%), and lower third (231 lesions, 48%) of the stomach.

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Table 3

Macroscopic features of the resected tumours

Submucosal invasion was found in 74 lesions on subsequent pathological examination by serial sections (fig 2). These patients were strongly recommended to undergo additional gastrectomy with D2 lymph node dissection. However, 30 patients were merely followed because of minute submucosal invasion, advanced age, other diseases, or the patient's refusal of an additional operation.

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Figure 2

Clinical courses after endoscopic mucosal resection (EMR) for early gastric cancer.

Among 405 intramucosal cancers, 278 (69%) were resected with a clear lateral margin (table 4). The rate of complete resection was lower when lesions had a diameter exceeding 20 mm and were situated in the upper third of the stomach (tables 4, 5). Forty three tumours were incompletely resected as there was definite invasion to the lateral margin endoscopically and histologically. Although EMR appeared to be successful endoscopically, 84 lesions could not be evaluated histologically because of diathermic burn, mechanical damage, or failure to retrieve multiple fragments.

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Table 4

Tumour size and invasion to the resection margin of intramucosal cancer

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Table 5

Tumour location and invasion to the resection margin of intramucosal cancer

Discussion

The EMR technique has been developed mainly in Japan where there is a high incidence of EGC. It is used infrequently in the West. It is important to carefully evaluate the current status of EMR and promote the appropriate use of this technique around the world. The number of patients undergoing EMR is increasing, with about 500 procedures performed in our hospital over the past 11 years. Considering that it generally takes one hour for resection and one week for admission, EMR is a minimally invasive procedure (a patient undergoing surgical resection is hospitalised for approximately three weeks). Our experience suggests that EMR can provide comparable long term survival rates to traditional therapy, provided adherence to strict inclusion criteria is followed. As shown in fig 3, the proportion of EGC cases treated by EMR at the NCCH has risen, and this accounted for about 40% of all EGC cases in 1998. This is probably due to improved diagnostic techniques.

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Figure 3

Trends in treatment for early gastric cancer at the National Cancer Center Hospital.

As there are still several unsolved problems in EMR, we will address specific concerns. Patient eligibility for EMR should be considered in relation to the risk of lymph node metastasis. As shown in table 1, EGCs fulfilling the criteria for EMR have a lower incidence of lymph node metastasis (0.36%) than the mortality rate of surgery for EGC (approximately 0.5% at the NCCH).

In this study, the Japanese Classification of Gastric Carcinoma was used for tumour description,1 which is widely used in our country. Western pathologists use the term “high grade dysplasia” for neoplastic lesions that have not breached the basement membrane to the lamina propria. Japanese pathologists, however, classify them as intramucosal cancer on the grounds that the cells are of a malignant type and have the potential to invade.11 A recent analysis showed that the histological type, macroscopic appearance, degree of invasion, and lymph node metastases are the same although many more EGCs are detected in Japan than in the West.12 We usually perform EMR for intramucosal cancer using the Japanese criteria, and it is important to have the same diagnostic criteria for gastric neoplastic lesions to propagate EMR around the world.

As it is sometimes difficult to accurately assess the depth of invasion prior to EMR, we remove any lesion without apparent endoscopic findings of submucosal invasion7 but 15% (74/479) of all lesions invaded to the submucosa. We do not use endoscopic ultrasonography routinely as it is not sensitive enough to evaluate minute invasion to the submucosa.

Although histological examination revealed minute submucosal invasion in resected EGC, some patients refused to undergo an additional treatment. As no lymph node metastasis was demonstrated in tumours with less than 300 μm of submucosal invasion,13 and no recurrence has been observed during follow up of these patients, it may be reasonable to treat patients with minute submucosal invasion by EMR.

In our series, most EMRs were performed by the so called “strip biopsy method”. However, we had five local recurrences in “complete resection”, all of which had been resected in multiple fragments by this method. Single fragment resection is preferable because with multifragment specimens it is often difficult to reconstruct the entire lesion. We believe it is likely that local recurrence can often be attributed to inappropriate assessment of the multiple fragments of resected specimens.

There have been several reports on endoscopic resection of larger lesions.14 ,15 In addition, we have found that the insulation tipped diathermy knife (IT knife) can allow safe resection of a larger lesion in a single piece. The average rate of complete resection increased to more than 90% and histological evaluation became easier following introduction of this technique.

A follow up programme is important for finding local recurrence and other cancers in the stomach. Thirteen metachronous early cancers were included in our series, which were diagnosed a median period of 23 months after the initial EMR (3–67 months).

The incidence of multiple primary lesions in surgically treated EGC is approximately 10% at the NCCH.16 As EGC is frequently associated with synchronous tumours that may be missed at an initial endoscopic examination, and the stomach may also contain premalignant conditions such as intestinal metaplasia, we should pay attention not only to recurrence but also to other cancers in the stomach.

In summary, based on our experience, it is clear that EMR can provide the same favourable long term survival rates as traditional therapy and is now the treatment of choice for mucosal EGC. We hope to promote its use around the world.