Clinical significance of histologic heterogeneity in submucosal invasive differentiated type gastric...
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J Gastroenterol 2001; 36:725–726 Editorial Clinical significance of histologic heterogeneity in submucosal invasive differentiated type gastric carcinoma with respect to endoscopic treatment Article on page 661 Risk factors for lymph node metastasis of submucosal invasive differentiated type gastric carcinoma: clinical significance of histological heterogeneity Mita T, Shimoda T of histologic heterogeneity in submucosal invasive differentiated type gastric carcinoma as a risk factor for nodal metastasis. Their study was based on histologic analysis of part of the intramucosal tumor in submu- cosal invasive gastric carcinoma. They demonstrated histologically that combined type differentiated submu- cosal invasive gastric carcinoma showed higher meta- static potential than histologically pure differentiated submucosal invasive gastric carcinoma, and they con- cluded that EMR should be limited to histologically pure differentiated carcinoma with submucosal inva- sion. These findings are very interesting and useful in understanding the malignant potential of submucosal invasive gastric carcinoma. However, there are several unresolved issues. The data of Mita and Shimoda 18 showed the invasion of lesions without lymph node metastasis to be only as deep as sm1 (500 µm). In term of considering EMR, the histologic heterogeneity of the tumor should be determined at the site of deepest submucosal invasion, as described above. As the pathologic features of intramucosal gastric carcinoma without lymph node metastasis have already been clarified, 1–10 examination of the histologic heterogeneity at the site of intramu- cosal carcinoma in submucosal invasive carcinoma may be meaningless. The part of the tumor that has meta- static potential could be considered to be the submuco- sally invasive part of the tumor. Immunohistochemical analysis should also be performed in the submucosally invasive part of the tumor. Although p53 and c-erbB2 expression were not shown to distinguish lesions with and without lymph node metastasis in the study of Mita and Shimoda, 18 this could be the result of failure to evaluate the site of submucosal invasion. In addition, even if lesions with lymph node metastasis show a significantly higher Ki-67 labeling index than lesions without lymph node metastasis, it is not practical to Curative endoscopic resection (endoscopic mucosal re- section; EMR) of early gastric carcinoma is performed for lesions such as intramucosal differentiated type adenocarcinomas less than 20 mm in diameter without ulceration. 1–5 Analysis of many surgical cases has shown that this type of early gastric carcinoma does not have metastatic lesions in the lymph nodes. 2–4,6 Moreover, long-term follow-up study has shown no significant sur- vival difference between those who received endoscopic treatment and those who had surgical treatments. 2,7 Undifferentiated type adenocarcinoma had never been indicated for endoscopic treatment, because lymph node metastasis sometimes occurs even at the stage of intramucosal carcinoma. 4,6,8 Recent studies have suggested that even undifferentiated type intra- mucosal carcinoma does not have lymph node meta- stasis if its maximum diameter is less than 10 mm and if there is no ulceration. 9 Surgical resection is now gen- erally used for submucosal invasive gastric carcinoma, because lymph node metastasis occurs in 10%–25% of patients. 3–6,10 To extend the indications for curative EMR of early gastric carcinoma, several studies have now been undertaken to clarify the risk factors for lymph node metastasis in differentiated type submucosal invasive adenocarcinoma, and definitive indications for curative EMR of submucosal invasive gastric carcinoma have been anticipated. 11,12 With this in mind, we reported the clinical significance of histologic heterogeneity of the tumor at the site of deepest invasion in gastric can- cer, 11,12 as well as in colorectal invasive carcinoma. 13–15 The tumor tissue at the site of deepest invasion was the region of a tumor with the highest malignant potential, being the part that ultimately will invade, spread locally, and metastasize. 13–17 In this issue of the Journal of Gastroenterology, Mita and Shimoda 18 report the clinical significance
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Transcript of Clinical significance of histologic heterogeneity in submucosal invasive differentiated type gastric...
J Gastroenterol 2001; 36:725–726
Editorial
Clinical significance of histologic heterogeneity in submucosal invasivedifferentiated type gastric carcinoma with respect toendoscopic treatment
Article on page 661Risk factors for lymph node metastasis of submucosal invasive differentiated type gastric carcinoma:clinical significance of histological heterogeneityMita T, Shimoda T
of histologic heterogeneity in submucosal invasivedifferentiated type gastric carcinoma as a risk factor fornodal metastasis. Their study was based on histologicanalysis of part of the intramucosal tumor in submu-cosal invasive gastric carcinoma. They demonstratedhistologically that combined type differentiated submu-cosal invasive gastric carcinoma showed higher meta-static potential than histologically pure differentiatedsubmucosal invasive gastric carcinoma, and they con-cluded that EMR should be limited to histologicallypure differentiated carcinoma with submucosal inva-sion. These findings are very interesting and useful inunderstanding the malignant potential of submucosalinvasive gastric carcinoma.
However, there are several unresolved issues. Thedata of Mita and Shimoda18 showed the invasion oflesions without lymph node metastasis to be only asdeep as sm1 (�500µm). In term of considering EMR,the histologic heterogeneity of the tumor should bedetermined at the site of deepest submucosal invasion,as described above. As the pathologic features ofintramucosal gastric carcinoma without lymph nodemetastasis have already been clarified,1–10 examinationof the histologic heterogeneity at the site of intramu-cosal carcinoma in submucosal invasive carcinoma maybe meaningless. The part of the tumor that has meta-static potential could be considered to be the submuco-sally invasive part of the tumor. Immunohistochemicalanalysis should also be performed in the submucosallyinvasive part of the tumor. Although p53 and c-erbB2expression were not shown to distinguish lesions withand without lymph node metastasis in the study of Mitaand Shimoda,18 this could be the result of failure toevaluate the site of submucosal invasion. In addition,even if lesions with lymph node metastasis show asignificantly higher Ki-67 labeling index than lesionswithout lymph node metastasis, it is not practical to
Curative endoscopic resection (endoscopic mucosal re-section; EMR) of early gastric carcinoma is performedfor lesions such as intramucosal differentiated typeadenocarcinomas less than 20 mm in diameter withoutulceration.1–5 Analysis of many surgical cases has shownthat this type of early gastric carcinoma does not havemetastatic lesions in the lymph nodes.2–4,6 Moreover,long-term follow-up study has shown no significant sur-vival difference between those who received endoscopictreatment and those who had surgical treatments.2,7
Undifferentiated type adenocarcinoma had neverbeen indicated for endoscopic treatment, becauselymph node metastasis sometimes occurs even at thestage of intramucosal carcinoma.4,6,8 Recent studieshave suggested that even undifferentiated type intra-mucosal carcinoma does not have lymph node meta-stasis if its maximum diameter is less than 10 mm andif there is no ulceration.9 Surgical resection is now gen-erally used for submucosal invasive gastric carcinoma,because lymph node metastasis occurs in 10%–25% ofpatients.3–6,10
To extend the indications for curative EMR ofearly gastric carcinoma, several studies have now beenundertaken to clarify the risk factors for lymph nodemetastasis in differentiated type submucosal invasiveadenocarcinoma, and definitive indications for curativeEMR of submucosal invasive gastric carcinoma havebeen anticipated.11,12 With this in mind, we reported theclinical significance of histologic heterogeneity of thetumor at the site of deepest invasion in gastric can-cer,11,12 as well as in colorectal invasive carcinoma.13–15
The tumor tissue at the site of deepest invasion was theregion of a tumor with the highest malignant potential,being the part that ultimately will invade, spread locally,and metastasize.13–17
In this issue of the Journal of Gastroenterology,Mita and Shimoda18 report the clinical significance
726 S. Tanaka: Histologic heterogeneity in sm invasive differentiated-type gastric ca and EMR
apply the Ki-67 labeling index to each individual casefor predicting lymph node metastasis. Moreover, it isnot possible to determine the histologic heterogeneityof a tumor before EMR. So, the criteria proposed byMita and Shimoda18 cannot be determined beforeEMR.
Finally, detailed examinations and nationwide collec-tion of data on the clinical significance of histologicheterogeneity such as that reported by Mita andShimoda18 will clarify the conditions necessary for cura-tive EMR of submucosal invasive differentiated-typegastric adenocarcinoma.
Shinji Tanaka, M.D., Ph.D.Department of Endoscopy, Hiroshima UniversitySchool of Medicine, 1-2-3 Kasumi, Minami-ku,Hiroshima 734-8551, Japan
References
1. Tada M, Shimada M, Yanai H. A new technique of gastric biopsy(in Japanese with English abstract). Stomach and Intestine1984;19:1107–16.
2. Tada M, Murakami A, Karita M, et al. Endoscopic resection ofearly gastric cancer. Endoscopy 1993;25:445–50.
3. Maehara Y, Orita H, Okuyama T, et al. Predictors of lymph nodemetastasis in early gastric cancer. Br J Surg 1992;79:245–7.
4. Sano T, Kobori O, Muto T. Lymph node metastasis from earlygastric cancer: endoscopic resection of tumour. Br J Surg 1992;79:241–4.
5. Inoue K, Tobe T, Kan N, et al. Problems in the definitionand treatment of early gastric cancer. Br J Surg 1991;78:818–21.
6. Oguro Y. Endoscopic treatment of early gastric cancer. DigEndosc 1991;3:3–15.
7. Takemoto T. Laser therapy of early gastric carcinoma. Endos-copy 1986;18:32–6.
8. Takemoto T, Tada M, Yanai H. Significance of strip biopsy withparticular reference to endoscopic mucosectomy. Dig Endosc1989;1:4–9.
9. The Japanese Gastric Cancer Association. Guidelines for thetreatment of gastric cancer. 2001.
10. Yasuda K, Mizuna Y, Kawai K. Endoscopic laser treatment forearly gastric cancer. Endoscopy 1993;25:451–4.
11. Nishida T, Tanaka S, Haruma K, et al. Histologic grade andcellular proliferation at the deepest invasive portion correlatewith the high malignancy of submucosal invasive gastric carci-noma. Oncology 1995;52:340–6.
12. Amioka T, Tanaka S, Haruma K, et al. Indication of endoscopictreatment for differentiated type of submucosal invasive gastriccarcinomas (in Japanese with English abstract). GastroenterolEndosc 2001;43:821–7.
13. Teixeira CR, Tanaka S, Haruma K, et al. The clinical significanceof the histologic subclassification of colorectal carcinoma. Oncol-ogy 1993;50:495–9.
14. Taniyama K, Suzuki H, Matsumoto M, et al. Relationships be-tween nodal status and cell kinetics, DNA ploidy pattern andhistopathology of the deeply infiltrating sites in colorectal adeno-carcinoma. Acta Pathol Jpn. 1993;43:590–6.
15. Tanaka S, Haruma K, Oh-e H, et al. Conditions of curability afterendoscopic resection for colorectal carcinoma with submucosallymassive invasion. Oncol Rep 2000;7:783–8.
16. Nishida T, Tanaka S, Haruma K, et al. The risk factors forlymph node metastasis in submucosal invasive gastric carcinoma.Assessment of the indication for endoscopic treatment (inJapanese with English abstract). Jpn J Gastroenterol 1994;91:1399–406.
17. Hirota T, Ochiai A, Itabashi M, et al. Significance of histologicaltype of gastric carcinoma as a prognostic factor (in Japanese withEnglish abstract). Stomach and Intestine 1991;26:1149–58.
18. Mita T, Shimoda S. Risk factors for lymph node metastasis ofsubmucosal invasive differentiated type gastric carcinoma: clini-cal significance of histological heterogeneity. J Gastroenterol2001;36:661–8.
