Annals of Surgical Oncology Cite Track
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Yasuda, K.
Right arrow Articles by Kitano, S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Yasuda, K.
Right arrow Articles by Kitano, S.
Related Collections
Right arrow Surgery
Annals of Surgical Oncology 9:192-196 (2002)
© 2002 Society of Surgical Oncology

ORIGINAL ARTICLES

Superficially Spreading Cancer of the Stomach

Kazuhiro Yasuda, MD, Masafumi Inomata, MD, Kyuzo Fujii, MD, Norio Shiraishi, MD, Yosuke Adachi, MD and Seigo Kitano, MD, FACS

From the Department of Surgery I, Oita Medical University, Oita, Japan.

Correspondence: Address correspondence and reprint requests to: Kazuhiro Yasuda, MD, Department of Surgery I, Oita Medical University, 1-1 Idaigaoka, Hasama-machi, Oita 879-5593, Japan; Fax: 81-97-549-6039; E-mail: kyasuda{at}oita-med.ac.jp


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Background: Superficially spreading cancer (SSC) of the stomach is rare and extends widely along the mucosa or submucosa of the stomach. This study was conducted to clarify the clinicopathologic characteristics and prognosis of patients with SSC.

Methods: SSC was defined as a tumor invading the mucosa or submucosa and measuring >=5 cm in size. The clinicopathologic findings and outcomes of 36 patients with SSC were compared with those of 300 patients with early gastric cancer (EGC) measuring <=5 cm and 271 with advanced gastric cancer measuring >=5 cm.

Results: SSC was significantly different from ordinary EGC in tumor size, frequency of lymph node metastasis, lymphatic invasion, venous invasion, and stage II, III, and IV disease. The frequency of serosal invasion, lymph node metastasis, and lymphatic and venous invasions in cases of SSC was significantly lower than with advanced gastric cancer. Although tumor size of SSC evaluated before operation was smaller than that on the resected specimen, the 10-year survival rate was not different between SSC and ordinary EGC.

Conclusions: SSC was characterized by high frequency of lymph node metastasis and preoperative underestimation of tumor size. SSC should be treated by a gastrectomy and lymphadenectomy with sufficient resection margin.

Key Words: Superficially spreading cancer • Early gastric cancer • Gastric cancer • Pathology • Prognosis • Surgery


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Recently, the detection of early gastric cancer (EGC) has increased because of improved diagnostic procedures and new widespread mass screenings.1,2 The prognosis after surgery for patients with EGC is favorable,3,4 and the effectiveness of endoscopic mucosal resection or laparoscopic local resection is widely accepted.5,6 Among EGC cases, however, the occurrence of exceptional tumors extending widely into the mucosa, submucosa, or both has been observed.

This entity was first reported by Stout7 in 1942 and was termed "superficial spreading type of carcinoma of the stomach." This tumor type is macroscopically characterized by reddening, irregularity, and slightly nodular mucosa. Kodama et al.8 and Inokuchi et al.9 classified EGC into superficially spreading type and penetrating growth type. Few comprehensive studies have evaluated the clinicopathologic characteristics and prognosis of patients with superficially spreading cancer (SSC) of the stomach.10,11

To clarify the characteristics and optimal treatment of SSC, the clinicopathologic findings and outcomes of patients with SSC were compared with those of patients with ordinary EGC and advanced gastric cancer (AGC). The features of SSC according to the major histological types were also examined.


   MATERIALS AND METHODS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
 DISCUSSION
 REFERENCES
 
From 1982 to 1999, 696 patients with primary gastric adenocarcinoma underwent surgery at the Department of Surgery I, Oita Medical University. Of these patients, 36 had SSC, 300 had EGC measuring <5 cm, and 271 had AGC measuring >=5 cm. SSC was defined as a tumor invading the mucosa or submucosa and measuring >=5 cm (Fig. 1). EGC was defined as a tumor limited to the mucosa or submucosa, whereas AGC was defined as a tumor invading the muscularis propria or deeper, regardless of the presence or absence of lymph node metastasis.12



View larger version (83K):
[in this window]
[in a new window]
  		FIG. 1. Superficially spreading cancer of the stomach. (A) Gross finding of the resected stomach. (B) Dark area shows wide area of mucosal cancer. (C) Histology revealed well-differentiated tubular adenocarcinoma widely spreading in the mucosa (hematoxylin and eosin, original magnification x10).

 
The age and sex of patients, location, size, gross type, and histological type of tumors, depth of wall invasion, lymph node metastasis, lymphatic and venous invasions, and stage of disease were obtained from the operation records and pathology reports. Preoperative evaluation of tumor size was made by barium meal study and gastric endoscopy, and tumor size was determined by measuring the maximal diameter of the resected specimen. Histological type was divided into well-differentiated type and poorly differentiated type.13 Gross appearance was classified into elevated (I, IIa) and depressed (IIb, IIc, III) type. Serosal invasion was defined as tumor invasion to the serosal surface or adjacent organs (T3). These clinicopathologic findings were based on the Japanese classification of gastric carcinoma outlined by the Japanese Gastric Cancer Association.12

All data were analyzed with the {chi}2 test or Student’s t-test. Survival rates were calculated by the Kaplan-Meier method and were assessed by the generalized Wilcoxon test. A P value of <.05 was regarded as statistically significant.


   RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
DISCUSSION
 REFERENCES
 
The incidence of SSC was 11% (36 of 336) in EGCs and 5% (36 of 696) in all gastric cancers. SSC, compared with EGC, was characterized by larger tumor size (6.6 vs. 2.3 cm; P < .01); more frequent lymph node metastasis (28% vs. 6%; P < .01); higher percentages of positive lymphatic invasion (33% vs. 17%; P < .05); positive venous invasion (8% vs. 2%; P < .05); and stage II, III, and IV disease (8% vs. 1%; P < .01; Table 1). When EGC was divided into three groups according to the tumor size (<1 cm, 1–3 cm, or 3–5 cm), the frequencies of submucosal invasion and lymph node metastasis of EGC were linked to tumor size (Fig. 2). The frequency of submucosal invasion of SSC was different from that of EGC measuring <1 cm (53% vs. 24%; P < .01), and the frequency of lymph node metastasis of SSC was different from that of EGC measuring <1 cm (28% vs. 0%; P < .01) and that of EGC measuring 1 to 3 cm (28% vs. 5%; P < .01).


View this table:
[in this window]
[in a new window]
  		TABLE 1. Superficially spreading cancer (SSC) versus early gastric cancer
 


View larger version (43K):
[in this window]
[in a new window]
  		FIG. 2. Depth of wall invasion (top) and status of lymph node metastasis (bottom) with reference to tumor size in EGC. The frequency of submucosal invasion was different between SSC and EGC measuring <1 cm, and the frequency of lymph node metastasis was different between SSC and EGC measuring <1 cm and between SSC and EGC measuring 1 to 3 cm. SSC, superficially spreading cancer; M, mucosal; SM, submucosal; N(-), node negative; N(+), node positive.

 
SSC, compared with AGC, was characterized by more frequent location in the lower two thirds of the stomach (92% vs. 72%; P < .01), smaller tumor size (6.6 vs. 8.6 cm; P < .01), lower percentages of serosal invasion (0% vs. 54%; P < .01), lymph node metastasis (28% vs. 81%; P < .01), and stage III or IV disease (8% vs. 68%; P < .01; Table 2). Tumor size was evaluated preoperatively in 27 patients with SSC, and tumor size predicted before operation was smaller than that measured on the resected specimen (4.6 ± 1.8 cm vs. 6.8 ± 2.2 cm; P < .01). However, the 10-year survival rate was not significantly different between patients with SSC and those with EGC (97.2% vs. 98.3%).


View this table:
[in this window]
[in a new window]
  		TABLE 2. Superficially spreading cancer (SSC) versus advanced gastric cancer (AGC)a
 
There were 21 well-differentiated SSCs and 15 poorly differentiated SSCs (Table 3). The well-differentiated tumors were predominant in men (81%), whereas the poorly differentiated tumors were predominant in women (60%). Depressed type comprised 62% of well-differentiated tumors, whereas it comprised 100% of poorly differentiated tumors. The 10-year survival rate was not significantly different between well-differentiated and poorly differentiated SSC (95.2% vs. 100%).


View this table:
[in this window]
[in a new window]
  		TABLE 3. Well- versus poorly differentiated type of superficially spreading cancera
 

   DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
REFERENCES
 
In this study, we clarified that SSC was characterized by location in the lower two thirds of the stomach, frequent lymph node metastasis, frequent lymphatic and venous invasions, and advanced stage. Although preoperative evaluation of tumor size was often insufficient, the 10-year survival rate of patients with SSC was high and comparable with that of patients with ordinary EGC.

SSC is a relatively rare entity among gastric cancers. The previously reported incidence of SSC was only 5% to 11% of EGCs and 2% to 4% of all gastric cancers.10,11,14 The incidence of SSC in our series (10% in EGC and 5% in all gastric cancers) was similar to that of these reports.

Kitamura et al.10 investigated 32 SSCs and reported that the frequencies of submucosal invasion (63%), lymph node metastasis (22%), and lymphatic invasion (16%) were higher in SSC than in cancers measuring <=2 cm. The Japanese-language literature contains several reports of SSC. Honda et al.14 examined 44 cases of SSC and showed higher frequencies of lymph node metastasis (16%) and lymphatic invasion (27%) in SSC than in ordinary EGC. Morita et al.15 studied 29 cases of EGC measuring >8 cm in size and found that SSC was associated with frequent submucosal invasion (66%) and lymph node metastasis (38%). Our study confirmed that the frequencies of lymph node metastasis (28%), lymphatic invasion (33%), and submucosal invasion were higher in SSC than in ordinary EGC.

Even when the depth of wall invasion is limited to the mucosa or submucosa, SSC has a high potential for metastasis to the lymph nodes. We previously showed that tumor size was closely linked to the degree of lymph node metastasis16 and that tumor size was correlated with the frequency of lymph node metastasis in EGC invading the submucosa.17 Therefore, gastrectomy with lymph node dissection is recommended for patients with SSC.11

Tumor size of SSC in our series was often underestimated preoperatively. The accuracy of preoperative evaluation of the extent of SSC is 90% by radiological examination and 79% by endoscopic examination.15 When treating SSC by gastrectomy, a sufficient resection margin is important.11 In SSC, the poorly differentiated type showed a female predominance and was associated with the grossly depressed type. These features are similar to those of ordinary EGC13,18 and are useful in the radiological or endoscopic diagnosis of SSC.

Clarification of the histogenesis and development of SSC is important. Bamba et al.19 studied the clonality of SSC and indicated that seven of nine SSCs were of monoclonal origin. Kodama et al.8 and Inokuchi et al.9 showed that the growth pattern of EGC was associated with clinical outcome: superficially spreading type had a favorable prognosis, whereas penetrating growth type had a poor outcome because of frequent liver metastasis. Haraguchi et al.20 studied the relationship between growth pattern and DNA ploidy and found that the superficially spreading type showed lower DNA ploidy more often than did the penetrating growth type. Recently, Tomoda et al.21 detected a lower microvessel density and less vascular endothelial growth factor in superficially spreading type than in penetrating growth type. Some gastric carcinomas with low DNA ploidy and weak secretion of vascular endothelial growth factor may spread widely in the mucosa without vertical invasion through the gastric wall. Further investigations, including molecular and biological studies, are required to clarify the morphogenesis and growth mechanism of SSC.

In conclusion, SSC was characterized by a high frequency of lymph node metastasis and preoperative underestimation of tumor size. The optimal treatment for SSC is gastrectomy and lymph node dissection with sufficient resection margin. Endoscopic mucosal resection or laparoscopic local resection should not be applied to SSC.22

Received for publication July 9, 2001. Accepted for publication October 12, 2001.


   REFERENCES
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 

  1. Ohta H, Noguchi K, Takagi M, Nishi T, Kajitani T, Kato Y. Early gastric carcinoma with special reference to macroscopic classification. Cancer 1987; 60: 1099–106.[CrossRef][Medline]
  2. Matsukuma A, Furusawa M, Tomoda H, Seo Y. A clinicopathological study of asymptomatic gastric cancer. Br J Cancer 1996; 74: 1647–50.[Medline]
  3. Nakamura K, Ueyama T, Yao T, et al. Pathology and prognosis of gastric carcinoma: findings of 10,000 patients who underwent primary gastrectomy. Cancer 1992; 70: 1030–7.[CrossRef][Medline]
  4. Adachi Y, Mori M, Maehara Y, Kitano S, Sugimachi K. Prognostic factors of node-negative gastric carcinoma: univariate and multivariate analyses. J Am Coll Surg 1997; 184: 373–7.[CrossRef][Medline]
  5. Ono H, Kudo H, Gotoda T, et al. Endoscopic mucosal resection for treatment of early gastric cancer. Gut 2001; 48: 225–9.[Abstract/Free Full Text]
  6. Ohgami M, Kumai K, Otani Y, Kubota T, Kitajima M. Laparoscopic wedge resection of the stomach for early gastric cancer using a lesion-lifting method. Dig Surg 1994; 11: 64–7.
  7. Stout AP. Superficial spreading type of carcinoma of the stomach. Arch Surg 1942; 44: 651–7.[CrossRef]
  8. Kodama Y, Inokuchi K, Soejima K, Matsusaka T, Okamura T. Growth patterns and prognosis in early gastric carcinoma. Cancer 1983; 51: 320–6.[CrossRef][Medline]
  9. Inokuchi K, Kodama Y, Sasaki O, Kamegawa T, Okamura T. Differentiation of growth patterns of early gastric carcinoma determined by cytophotometric DNA analysis. Cancer 1983; 51: 1138–41.[Medline]
  10. Kitamura K, Yamaguchi T, Okamoto K, Nishida T, Takahashi T. Superficial spreading type of early gastric cancer. Br J Cancer 1996; 74: 1834–7.[Medline]
  11. Kasakura Y, Fujii M, Mochizuki F, Imai S, Kanamori N, Suzuki T. Clinicopathological features of the superficial spreading type of early gastric cancer. Gastric Cancer 1999; 2: 129–35.[Medline]
  12. Japanese Gastric Cancer Association. Japanese classification of gastric carcinoma: 2nd English ed. Gastric Cancer 1998; 1: 10–24.[Medline]
  13. Adachi Y, Yasuda K, Inomata M, Sato K, Shiraishi N, Kitano S. Pathology and prognosis of gastric carcinoma: well versus poorly differentiated type. Cancer 2000; 89: 1418–24.[CrossRef][Medline]
  14. Honda T, Takeshita K, Tani M, et al. Clinicopathological and endoscopic evaluation of the superficial spreading type of early gastric cancer (in Japanese, with English abstract). Prog Dig Endosc 1990; 36: 203–7.
  15. Morita H, Baba Y, Sakai T, et al. Preoperative radiologic and endoscopic diagnosis of the superficially spread type early gastric cancer (in Japanese, with English abstract). Stomach Intest 1996; 31: 581–93.
  16. Adachi Y, Oshiro T, Mori M, Maehara Y, Sugimachi K. Tumor size as a simple prognostic indicator for gastric carcinoma. Ann Surg Oncol 1997; 4: 137–40.[Abstract]
  17. Yasuda K, Shiraishi N, Suematsu T, Yamaguchi K, Adachi Y, Kitano S. Rate of detection of lymph node metastasis is correlated with the depth of submucosal invasion in early stage gastric carcinoma. Cancer 1999; 85: 2119–23.[CrossRef][Medline]
  18. Sugano H, Nakamura K, Kato Y. Pathological studies of human gastric cancer. Acta Pathol Jpn 1982; 32 (Suppl): 329–47.
  19. Bamba M, Sugihara H, Okada K, Bamba T, Hattori T. Clonal analysis of superficial depressed-type gastric carcinoma in humans. Cancer 1998; 83: 867–75.[CrossRef][Medline]
  20. Haraguchi M, Korenaga D, Kakeji Y, Orita H, Maehara Y, Sugimachi K. DNA ploidy is associated with growth potential in gastric carcinoma. Cancer 1991; 68: 2608–11.[Medline]
  21. Tomoda M, Maehara Y, Kakeji Y, Ohno S, Ichiyoshi Y, Sugimachi K. Intratumoral neovascularization and growth pattern in early gastric carcinoma. Cancer 1999; 85: 2340–6.[CrossRef][Medline]
  22. Kunisaki C, Shimada H, Nomura M, Akiyama H. Appropriate lymph node dissection for early gastric cancer based on lymph node metastases. Surgery 2001; 129: 153–7.[CrossRef][Medline]




This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Yasuda, K.
Right arrow Articles by Kitano, S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Yasuda, K.
Right arrow Articles by Kitano, S.
Related Collections
Right arrow Surgery

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS