Controversy Concerning the Cutoff Value for Depth of Submucosal Invasion after Endoscopic Mucosal Resection of Early Gastric Cancer

We read with interest the recent article by the Endoscopic Classification Review Group [1]. Endoscopic mucosal resection (EMR) has become widely accepted as a curative treatment for mucosal cancer of the stomach [2], and recent advances in EMR techniques are extremely remarkable. A new endoscopic procedure, using multiple accessories, provides an en bloc specimen and therefore allows precise histologic staging.

According to the Paris Workshop report [3] and the recent review by the Endoscopic Classification Review Group, the risk of nodal metastasis is low when the depth of invasion into the submucosa is less than a cutoff value. In EMR specimens from the stomach, the cutoff value is 500 μm. The Paris Workshop adopted the cutoff value given in an article by Kashimura et al. [4]. Also, a recent review by the Endoscopic Classification Review Group accepted the same cutoff value on the basis of an article by Gotoda et al. [5]. This cutoff value was not obtained from EMR specimens but from surgically resected gastric tumors. It is questionable whether the cutoff value from surgical specimens can be applied to EMR specimens. In general, the depth of the submucosa is variable, and there are many differences between specimens obtained from EMR and surgery. To evaluate the depth of invasion precisely, the tissue specimen obtained after EMR should be gently stretched, and then pinned on cardboard, in the endoscopy unit. To see whether the 500 µm cutoff value could be applied to specimens obtained from EMR, we performed a series of studies. We took two identically sized pieces of porcine gastric antrum. One was fixed without extension on cardboard and measured 2 cm × 2 cm. The other, stretched fully on cardboard, measured 3 cm × 3 cm. After a 1-day fixation period and use of Masson’s trichrome stain, the depth of the submucosa was measured. In the unstretched 2 cm × 2 cm specimen the depth of the submucosa was 500 µm, and in the fully stretched specimen it was 200 µm. We also investigated the change in the depth of the submucosa in six specimens obtained from three different areas of a human stomach. Of the two pieces obtained from the gastric antrum, one was fixed on cardboard and measured 2.5 cm × 1.0 cm. The other, fully stretched piece measured 3.0 cm × 1.7 cm. The depth of the submucosa decreased from 620 - 650 µm to 250 - 300 µm (Figure [1]). Of the two pieces from the greater curvature of the gastric body, one was 2.5 cm × 0.8 cm and the other 3.0 cm × 1.7 cm; the submucosal depth decreased from 650 - 700 µm to 300 µm (Figure [2]). The same results were found with the specimens from the lesser curvature of the gastric body: one was 2.5 cm × 1.3 cm and the other was 3.2 cm × 1.7 cm, with a decrease in submucosal depth from 400 - 450 µm to 350 - 400 µm (Figure [3]).

Figure 1 Unstretched (left) and stretched (right) specimens from human gastric antrum. mm, muscularis mucosae; sm, submucosa; pm, muscularis propria.

Figure 2 Unstretched (left) and stretched (right) specimens from greater curvature of human gastric body.

Figure 3 Unstretched (left) and stretched (right) specimens from lesser curvature of human gastric body.

In summary, there is controversy over the cutoff value for depth of submucosal invasion in EMR specimens. This is because the depth of the submucosa decreases as the specimen is stretched, and because this depth does not show a constant value in different portions of the stomach. It is our opinion that after EMR of early gastric cancer, the cutoff value for depth of submucosal invasion is less than 500 µm in the fully stretched EMR specimen.

Competing interests: None

References

• 1 Endoscopic Classification Review Group . Update on the Paris classification of superficial neoplastic lesions in the digestive tract.  Endoscopy. 2005;  37 570-578
• 2 Cho J Y. Indications and limitations of endoscopic mucosal resection in gastric cancer [in Korean].  Korean J Gastroenterol. 2005;  45 3-8
• 3 The Paris endoscopic classification of superficial neoplastic lesions . Esophagus, stomach, and colon.  Gastrointest Endosc. 2003;  58 S3
• 4 Kashimura H, Watanabe H, Yoichi A jioka . et al . The risk factors for nodal micrometastasis of submucosal invasive gastric carcinoma with special reference to assessment of the indication for endoscopic treatment.  Gastric Cancer. 1999;  2 33-39
• 5 Gotoda T, Yanagisawa A, Sasako M. et al . Incidence of lymph node metastasis from early gastric cancer: estimation with a large number of cases at two large centers.  Gastric Cancer. 2000;  3 219-225