- Email: [email protected]
Clinicopathological features and medical management of early gastric cancer
The American Journal of Surgery 195 (2008) 229 –232
Clinical surgery—International
Clinicopathological features and medical management of early gastric cancer Takehiro Okabayashi, M.D.*, Michiya Kobayashi, M.D., Isao Nishimori, M.D., Takeki Sugimoto, M.D., Tsutomu Namikawa, M.D., Saburo Onishi, M.D., Kazuhiro Hanazaki, M.D. Kochi Medical School, Kohasu-Okocho, Nankoku, 783-85050 Kochi, Japan Manuscript received September 1, 2006; revised manuscript February 20, 2007
Abstract Background: The detection of early gastric carcinoma (EGC) has increased worldwide due to advances in endoscopic techniques and equipment. The aim of the current study was to compare the clinicopathological findings of patients with and without lymph node metastasis. Methods: A total of 440 cases of early gastric carcinoma in patients who underwent surgical procedures between 1981 and 2002 at Kochi Medical School were studied. Results: Lymph node metastasis was observed in 38 patients (8.6%) with EGC. Multivariate analysis identified 4 independent risk factors of lymph node metastasis: (1) submucosal invasion; (2) tumor diameter greater than 3.5 cm; (3) the presence of vascular invasion; and (4) the presence of lymphatic permeation. Conclusion: For patients with tumor size between 1 cm and 3.5 cm we would recommend endoscopic resection initially, with a consideration for additional surgical resection if microscopic vascular invasion or lymphatic permeation is demonstrated. © 2008 Excerpta Medica Inc. All rights reserved. Keywords: Early gastric carcinoma; Lymph node metastasis; Gastrectomy; Less invasive surgery; Cohort study
Early gastric carcinoma (EGC) is defined as a lesion of the stomach confined to the mucosa and/or submucosa, regardless of lymph node metastatic status. The primary reasons for earlier detection of EGC is the use of screening endoscopy in high risk patient population, including advances in endoscopic technique and equipment [1–3]. Lymph node metastasis is one of the most important prognostic factors for EGC. Excellent curative treatment for patients with EGC has been obtained with regional lymphadenectomy [4 –7]. Recently, less invasive treatments have been performed for EGC, including endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) [8 –11]. Such methods of limited surgery for EGC should be considered when deciding on a treatment method for EGC [12–15]. This study was designed to investigate the clinicopathological characteristics of EGC, to identify factors associated with lymph node metastasis. Using these predictive factors for lymph node metastasis, we established criteria for the medical management of EGC. * Corresponding author. Tel.: ⫹81-88-880-2330; fax: 81-88-880-2371. E-mail address: [email protected]
Patients and Methods A total of 440 patients who underwent surgery as an initial treatment for solitary early gastric carcinoma between 1981 and 2002 at Kochi Medical School were studied. Of these patients, 295 were men and 145 were women, ranging in age from 20 to 98 years (mean 64.5). Curative resection was the operative aim for all patients. Gastric carcinomas were classified using the Japanese Classification of Gastric Carcinoma reference [16]. The stomach was anatomically divided into 3 portions: the upper third, the middle third, and the lower third. Postoperative clinicopathological parameters, including age, gender, tumor size, location in the stomach, macroscopic type, depth of gastric carcinoma infiltration, and histological classification, were evaluated. Based on these parameters, predictive factors for lymph node metastasis of EGC were investigated and potential management strategies for EGC were considered accordingly. Statistical analysis Clinicopathological findings were compared by using t tests, Pearson chi-square tests, and Aspin-Welch tests. Where appropriate, values were expressed as mean ⫾ SD. A
0002-9610/08/$ – see front matter © 2008 Excerpta Medica Inc. All rights reserved. doi:10.1016/j.amjsurg.2007.02.025
230
T. Okabayashi et al. / The American Journal of Surgery 195 (2008) 229 –232
Table 1 Comparison of clinicopathologic findings between patients with nodenegative tumor and node-positive tumor Characteristics
Node-negative Node-positive P (n ⫽ 402) (n ⫽ 38) value
Overall (%) Age in years (mean ⫾ SD) Gender: male (%) Tumor size in cm (mean ⫾ SD) Tumor location (%) Upper third Middle third Lower third Macroscopic type (%) Elevated Flat Depressed Histological classification (%) Differentiated Undifferentiated Depth of invasion (%) Intramucosal Submucosal Presence of vascular invasion (%) Presence of lymphatic permeation (%)
91.4 62.3 ⫾ 12.3 271 (67.4) 3.3 ⫾ 2.0
8.6 63.0 ⫾ 1.8 24 (63.2) 4.4 ⫾ 1.8
37 (9.2) 125 (31.1) 240 (59.7)
3 (7.9) 12 (31.6) 23 (6.5)
.965
115 (28.6) 58 (14.4) 229 (57.0)
12 (31.6) 7 (18.4) 19 (5.0)
.677
276 (68.7) 126 (31.3)
20 (52.6) 18 (47.4)
.044
221 (55.0) 181 (45.0) 53 (13.2)
2 (5.3) 36 (94.7) 14 (36.8)
⬍.01
96 (23.9)
34 (89.5)
⬍.01
.764 .594 .002
⬍.01
value of P ⬍.05 was considered significant. A multivariate logistic regression was used to identify factors that were associated independently with lymph node metastasis. Results Table 1 summarizes the study population. From 440 patients with EGC, including intramucosal and submucosal invasive gastric carcinoma, 402 patients (91.4%) were negative for lymph node metastasis and 38 (8.6%) were positive. In univariate analysis using sex, gender, location in the stomach, and macroscopic type, no significant difference in the incidence of lymph node metastasis was found. Histologically, EGC with lymph node metastasis was significantly larger than that without (P ⫽ .002). Receiver operator characteristic curve analysis indicated the optimal cut-off value for the size of the tumor to be 3.5 cm, yielding 6.5% sensitivity and 73.6% specificity for occurrence of lymph node metas-
Fig. 1. Receiver operator characteristic curve analysis indicated the optimal cut-off value for the size of the tumor to be 3.5 cm, yielding 6.5% sensitivity and 73.6% specificity for occurrence of lymph node metastasis.
Fig. 2. Multivariate analysis of risk factors for lymph node metastasis -box and whiskers type summary plot showing the multivariate results.
tasis (P ⫽ .047) (Fig. 1). Parameters indicative of pathological status were compared for patients with and without lymph node metastasis (Table 1). Of the parameters analyzed, significant differences between the 2 groups were observed when comparing the occurrence of undifferentiated adenocarcinoma, the presence of vascular invasion, and lymphatic permeation. Five parameters shown by the univariate analysis to be significantly different between EGC with and without lymph node metastasis were further analyzed by multivariate logistic regression (Fig. 2). Consequently, 4 parameters were identified as independent markers for the occurrence of lymph node metastasis: (1) submucosal invasion (odds ratio [OR] 1.5; 95% confidence interval [CI] 2.7– 4.4; P ⬍.01); (2) tumor diameter greater than 3.5 cm (OR 7.8; CI 3.7–16.6; P ⬍ .01); (3) the presence of vascular invasion (OR 3.8; CI 1.9 –7.9; P ⬍ .01); and (4) the presence of lymphatic permeation (OR 27.1; CI 9.4 –78.3; P ⬍ .01). Comments Gastric carcinoma is the second most common malignancy worldwide, and surgical treatment remains the only curative management option. The incidence of early gastric carcinoma (EGC) has gradually increased with advances in diagnostic techniques and equipment [1–3]. In the West, EGC accounts for 4% to 16% of all gastric carcinoma cases [4,7], while in Japan the proportion of EGC is approximately 30% to 50% [4,7,9]. Lymph node metastases occur during the early stage of gastric carcinoma, and regional lymphadenectomy is recommended for surgical treatment of this disease. Excellent curative treatment for patients with EGC has been obtained with regional lymphadenectomy [4 –7]. Previous authors have reported that lymph node metastasis was one of the most important factors in determining the prognosis of patients with EGC, and the incidence of lymph node metastasis was 5.7% to 20% [5,7,9,10,17–23]. In this series, the incidences of lymph node metastasis in intramucosal invasive gastric carcinomas and in submucosal invasive gastric carcinomas were .9% and 16.6%, respectively. In this analysis of a consecutive series of EGC cases from a single institution, we identified 4 independent predictive factors for lymph node metastases. Two of these were submocosal invasion and tumor diameter greater than 3.5 cm, which has also been reported as
T. Okabayashi et al. / The American Journal of Surgery 195 (2008) 229 –232
Fig. 3. A proposed patient management algorithm for patients with early gastric cancer.
a risk factor in previous studies [10,11]. In patients with EGC, there was a high correlation in the incidence of lymph node metastases between the size of the tumor and submucosal invasion (r ⫽ 1.00). This might be explained by the tendency of larger EGCs to invade the submucosal layer. In EGC with tumor size less than 1 cm in diameter, lymph node metastasis was not detected, regardless of the depth or histological classification. This may suggest a reduced metastatic capability of tumors smaller than 1 cm. Other parameters that we identified as risk factors for lymph node metastases included the presence of lymphatic permeation or vascular invasion. A close correlation has been demonstrated between histologically undifferentiated tumors and the incidence of lymph node metastasis in EGC [7,17,24,25]; however, our study did not reveal the histological type as an independent marker for lymph node metastasis after multivariate analysis. This result suggests that adenocarcinoma of the stomach at the early stage does not have greater lymphogenic or hematological malignant potential with lymph node metastatic capability regardless of histological classification including differentiated adenocarcinoma and undifferentiated adenocarcioma. The incidence of lymph node metastasis of EGC was 8.6% in this consecutive series of 440 gastrectomy cases from a single institution. Multivariate analysis comparing patients with and without lymph node metastasis identified 4 independent risk factors for lymph node metastasis: (1) submucosal invasive tumor; (2) tumor diameter greater than 3.5 cm; (3) the presence of vascular invasion; and (4) the presence of lymphatic permeation. Because surgical resection of the stomach may be associated with poorer outcome in terms of quality of life [26], we suggest a therapeutic pathway for the management of EGC that may reduce the need for larger surgical procedures in some patients (Fig. 3). Experienced endoscopists are able to accurately evaluate the extent of lesions in gastric carcinoma, and therefore, less invasive treatment, such as EMR or ESD, may become possible for EGC with tumors less than 3.5 cm in diameter [8 –15]. Because the exact tumor
231
diameter is not always easy to determine endoscopically, the endoscopic scale for measuring the size of the EGC and endoscopic ultrasonography might be useful [27]. EMR and ESD have become a reasonable and convenient diagnostic and treatment modality, because histological information about the whole tumor can be obtained and furthermore, a curative treatment is achieved in case of localized tumors without lymph node metastasis, preserving the whole stomach [28]. In recent years, EMR and/or ESD are a good and safe curative treatment option with feasible clinical outcomes in patients with EGC. We considered that EMR and/or ESD ensured an excellent prognosis, and should be the first choice of treatment in patients with EGC, although careful histological examination and long-term endoscopic surveillance are important [29,30]. However, when lymphatic permeation or vascular invasion is recognized in post-resection specimens, additional surgical resection of the stomach with lymphadenectomy would be recommended. Further prospective studies are warranted to evaluate the efficacy of this therapeutic strategy. In conclusion, patients with EGC with tumors of diameters less than 1 cm are probably the best candidates for endoscopic resection, whereas those with tumors greater than 3.5 cm should undergo gastrectomy with regional lymphadenectomy. For patients with tumor size between 1 cm and 3.5 cm we would recommend endoscopic resection initially, with a consideration for additional surgical resection if microscopic vascular invasion or lymphatic permeation was demonstrated. References [1] Huguier M, Ferro L, Barrier A. Early gastric carcinoma: spread and multicentricity. Gastric Cancer 2002;5:125– 8. [2] Seto Y, Shimoyama S, Kitayama J, et al. Lymph node metastasis and preoperative diagnosis of depth of invasion in early gastric cancer. Gastric Cancer 2001;4:34 – 8. [3] Okabayashi T, Gotoda T, Kondo H, et al. Usefulness of indigo carmine chromoendoscopy and endoscopic clipping for accurate preoperative assessment of proximal gastric cancer. Endoscopy 2000;32:S62. [4] Piso P, Werner U, Benten D, et al. Early gastric cancer— excellent prognosis after curative resection in 87 patients irrespective of submucosal infiltration, lymph-node metastases or tumor size. Langenbecks Arch Surg 2001;386:26 –33. [5] Popiela T, Kulig J, Kolodziejczyk P, et al. Long-term results of surgery for early gastric cancer. Br J Surg 2002;89:1035– 42. [6] Basili G, Nesi G, Barchielli A, et al. Pathologic features and longterm results in early gastric cancer: report of 116 cases 8 –13 years after surgery. World J Surg 2003;27:149 –52. [7] Borie F, Millat B, Fingerhut A, et al. Lymphatic involvement in early gastric cancer. Arch Surg 2000;135:1218 –23. [8] Shimada S, Yagi Y, Shiomori K, et al. Characterization of early gastric cancer and proposal of the optimal therapeutic strategy. Surgery 2001;129:714 –9. [9] Folli S, Margagni P, Roviello F, et al. Risk factors for lymph node metastases and their prognostic significance in early gastric cancer (EGC) for the Italian Research Group for Gastric Cancer (IRGGC). Jpn J Clin Oncol 2001;31:495–9. [10] Abe N, Mori T, Takeuchi H, et al. Laparoscopic lymph node dissection after endoscopic submucosal dissection: a novel and minimally invasive approach to treating early stage gastric cancer. Am J Surg 2005;190:496 –503. [11] Abe N, Watanabe T, Sugiyama M, et al. Endoscopic treatment or surgery for undifferentiated early gastric cancer? Am J Surg 2004; 188:181– 4. [12] Tsujitani S, Oka S, Saito H, et al. Less invasive surgery for early gastric cancer based on the low probability of lymph node metastasis. Surgery 1999;125:148 –54.
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[13] Kunisaki C, Shimada H, Nomura M, et al. Appropriate lymph node dissection for early gastric cancer based on lymph node metastases. Surgery 2001;129:153–7. [14] Noguchi Y, Morinaga S, Yamamoto Y, et al. Is there a role for nontraditional resection of early gastric cancer? Surg Oncol Clin N Am 2002;11:387– 403. [15] Yoshikawa T, Tsuburaya A, Kobayashi O, et al. Is D2 lymph node dissection necessary for early gastric cancer? Ann Surg Oncol 2002; 9:401–5. [16] Japanese classification of gastric carcinoma—2nd English edition. Gastric Cancer 1998;1:10 –24. [17] Wu CY, Chen JT, Chen GH, et al. Lymph node metastasis in early gastric cancer: clinicopathological analysis. Hepatogastroenterology 2002;49:1465– 8. [18] Arai K, Iwasaki Y, Takahashi T. Clinicopathological analysis of early gastric cancer with solitary lymph node metastasis. Br J Surg 2002; 89:1435–7. [19] Choi HJ, Kim YH, Kim SS, et al. Occurrence and prognostic implications of micrometastases in lymph nodes from patients with submucosal gastric carcinoma. Ann Surg Oncol 2002;9:13–9. [20] Shimada S, Yagi Y, Honmyo U, et al. Involvement of three or more lymph nodes predicts poor prognosis in submucosal gastric carcinoma. Gastric Cancer 2001;4:54 –9. [21] Seto Y, Shimoyama S, Kitayama J, et al. Lymph node metastasis and preoperative diagnosis of depth of invasion in early gastric cancer. Gastric Cancer 2001;4:34 – 8.
[22] Morgagni P, Saragoni L, Folli S, et al. Lymph node micrometastases in patients with early gastric cancer: experience with 139 patients. Ann Surg Oncol 2001;8:170 – 4. [23] Lee E, Chae Y, Kim I, et al. Prognostic relevance of immunohistochemically detected lymph node micrometastasis in patients with gastric carcinoma. Cancer 2002;94:2867–73. [24] Hyung WJ, Noh SH, Lee JH, et al. Early gastric carcinoma with signet ring cell histology. Cancer 2002;94:78 – 83. [25] Adachi Y, Yasuda K, Inomata M, et al. Clinicopathologic study of early-stage mucinous gastric carcinoma. Cancer 2001;91:698 –703. [26] Blazeby JM, Metcalfe C, Nicklin J, et al. Association between quality of life scores and short-term outcome after surgery for cancer of the oesophagus or gastric cardia. Br J Surg 2005;92:1502–7. [27] Sabet EA, Okai T, Minamoto T, et al. Visualizing the gastric wall with a 30-MHz ultrasonic miniprobe: ex vivo imaging of normal gastric sites and sites of early gastric cancer. Abdom Imaging 2003; 28:252– 6. [28] Fijishiro M. Endoscopic submucosal dissection for stomach neoplasms. World J Gastroenterol 2006;12:5108 –12. [29] Youn JC, Youn YH, Kim TI, et al. Factors affecting long-term clinical outcomes of endoscopic mucosal resection of early gastric cancer. Hepatogastroenterology 2006;53:643–7. [30] Uedo N, Iishi H, Tatsuta M, et al. Long term outcomes after endoscopic mucosal resection for early gastric cancer. Gastric Cancer 2006;9:88 –92.
Clinical surgery—International
Clinicopathological features and medical management of early gastric cancer Takehiro Okabayashi, M.D.*, Michiya Kobayashi, M.D., Isao Nishimori, M.D., Takeki Sugimoto, M.D., Tsutomu Namikawa, M.D., Saburo Onishi, M.D., Kazuhiro Hanazaki, M.D. Kochi Medical School, Kohasu-Okocho, Nankoku, 783-85050 Kochi, Japan Manuscript received September 1, 2006; revised manuscript February 20, 2007
Abstract Background: The detection of early gastric carcinoma (EGC) has increased worldwide due to advances in endoscopic techniques and equipment. The aim of the current study was to compare the clinicopathological findings of patients with and without lymph node metastasis. Methods: A total of 440 cases of early gastric carcinoma in patients who underwent surgical procedures between 1981 and 2002 at Kochi Medical School were studied. Results: Lymph node metastasis was observed in 38 patients (8.6%) with EGC. Multivariate analysis identified 4 independent risk factors of lymph node metastasis: (1) submucosal invasion; (2) tumor diameter greater than 3.5 cm; (3) the presence of vascular invasion; and (4) the presence of lymphatic permeation. Conclusion: For patients with tumor size between 1 cm and 3.5 cm we would recommend endoscopic resection initially, with a consideration for additional surgical resection if microscopic vascular invasion or lymphatic permeation is demonstrated. © 2008 Excerpta Medica Inc. All rights reserved. Keywords: Early gastric carcinoma; Lymph node metastasis; Gastrectomy; Less invasive surgery; Cohort study
Early gastric carcinoma (EGC) is defined as a lesion of the stomach confined to the mucosa and/or submucosa, regardless of lymph node metastatic status. The primary reasons for earlier detection of EGC is the use of screening endoscopy in high risk patient population, including advances in endoscopic technique and equipment [1–3]. Lymph node metastasis is one of the most important prognostic factors for EGC. Excellent curative treatment for patients with EGC has been obtained with regional lymphadenectomy [4 –7]. Recently, less invasive treatments have been performed for EGC, including endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) [8 –11]. Such methods of limited surgery for EGC should be considered when deciding on a treatment method for EGC [12–15]. This study was designed to investigate the clinicopathological characteristics of EGC, to identify factors associated with lymph node metastasis. Using these predictive factors for lymph node metastasis, we established criteria for the medical management of EGC. * Corresponding author. Tel.: ⫹81-88-880-2330; fax: 81-88-880-2371. E-mail address: [email protected]
Patients and Methods A total of 440 patients who underwent surgery as an initial treatment for solitary early gastric carcinoma between 1981 and 2002 at Kochi Medical School were studied. Of these patients, 295 were men and 145 were women, ranging in age from 20 to 98 years (mean 64.5). Curative resection was the operative aim for all patients. Gastric carcinomas were classified using the Japanese Classification of Gastric Carcinoma reference [16]. The stomach was anatomically divided into 3 portions: the upper third, the middle third, and the lower third. Postoperative clinicopathological parameters, including age, gender, tumor size, location in the stomach, macroscopic type, depth of gastric carcinoma infiltration, and histological classification, were evaluated. Based on these parameters, predictive factors for lymph node metastasis of EGC were investigated and potential management strategies for EGC were considered accordingly. Statistical analysis Clinicopathological findings were compared by using t tests, Pearson chi-square tests, and Aspin-Welch tests. Where appropriate, values were expressed as mean ⫾ SD. A
0002-9610/08/$ – see front matter © 2008 Excerpta Medica Inc. All rights reserved. doi:10.1016/j.amjsurg.2007.02.025
230
T. Okabayashi et al. / The American Journal of Surgery 195 (2008) 229 –232
Table 1 Comparison of clinicopathologic findings between patients with nodenegative tumor and node-positive tumor Characteristics
Node-negative Node-positive P (n ⫽ 402) (n ⫽ 38) value
Overall (%) Age in years (mean ⫾ SD) Gender: male (%) Tumor size in cm (mean ⫾ SD) Tumor location (%) Upper third Middle third Lower third Macroscopic type (%) Elevated Flat Depressed Histological classification (%) Differentiated Undifferentiated Depth of invasion (%) Intramucosal Submucosal Presence of vascular invasion (%) Presence of lymphatic permeation (%)
91.4 62.3 ⫾ 12.3 271 (67.4) 3.3 ⫾ 2.0
8.6 63.0 ⫾ 1.8 24 (63.2) 4.4 ⫾ 1.8
37 (9.2) 125 (31.1) 240 (59.7)
3 (7.9) 12 (31.6) 23 (6.5)
.965
115 (28.6) 58 (14.4) 229 (57.0)
12 (31.6) 7 (18.4) 19 (5.0)
.677
276 (68.7) 126 (31.3)
20 (52.6) 18 (47.4)
.044
221 (55.0) 181 (45.0) 53 (13.2)
2 (5.3) 36 (94.7) 14 (36.8)
⬍.01
96 (23.9)
34 (89.5)
⬍.01
.764 .594 .002
⬍.01
value of P ⬍.05 was considered significant. A multivariate logistic regression was used to identify factors that were associated independently with lymph node metastasis. Results Table 1 summarizes the study population. From 440 patients with EGC, including intramucosal and submucosal invasive gastric carcinoma, 402 patients (91.4%) were negative for lymph node metastasis and 38 (8.6%) were positive. In univariate analysis using sex, gender, location in the stomach, and macroscopic type, no significant difference in the incidence of lymph node metastasis was found. Histologically, EGC with lymph node metastasis was significantly larger than that without (P ⫽ .002). Receiver operator characteristic curve analysis indicated the optimal cut-off value for the size of the tumor to be 3.5 cm, yielding 6.5% sensitivity and 73.6% specificity for occurrence of lymph node metas-
Fig. 1. Receiver operator characteristic curve analysis indicated the optimal cut-off value for the size of the tumor to be 3.5 cm, yielding 6.5% sensitivity and 73.6% specificity for occurrence of lymph node metastasis.
Fig. 2. Multivariate analysis of risk factors for lymph node metastasis -box and whiskers type summary plot showing the multivariate results.
tasis (P ⫽ .047) (Fig. 1). Parameters indicative of pathological status were compared for patients with and without lymph node metastasis (Table 1). Of the parameters analyzed, significant differences between the 2 groups were observed when comparing the occurrence of undifferentiated adenocarcinoma, the presence of vascular invasion, and lymphatic permeation. Five parameters shown by the univariate analysis to be significantly different between EGC with and without lymph node metastasis were further analyzed by multivariate logistic regression (Fig. 2). Consequently, 4 parameters were identified as independent markers for the occurrence of lymph node metastasis: (1) submucosal invasion (odds ratio [OR] 1.5; 95% confidence interval [CI] 2.7– 4.4; P ⬍.01); (2) tumor diameter greater than 3.5 cm (OR 7.8; CI 3.7–16.6; P ⬍ .01); (3) the presence of vascular invasion (OR 3.8; CI 1.9 –7.9; P ⬍ .01); and (4) the presence of lymphatic permeation (OR 27.1; CI 9.4 –78.3; P ⬍ .01). Comments Gastric carcinoma is the second most common malignancy worldwide, and surgical treatment remains the only curative management option. The incidence of early gastric carcinoma (EGC) has gradually increased with advances in diagnostic techniques and equipment [1–3]. In the West, EGC accounts for 4% to 16% of all gastric carcinoma cases [4,7], while in Japan the proportion of EGC is approximately 30% to 50% [4,7,9]. Lymph node metastases occur during the early stage of gastric carcinoma, and regional lymphadenectomy is recommended for surgical treatment of this disease. Excellent curative treatment for patients with EGC has been obtained with regional lymphadenectomy [4 –7]. Previous authors have reported that lymph node metastasis was one of the most important factors in determining the prognosis of patients with EGC, and the incidence of lymph node metastasis was 5.7% to 20% [5,7,9,10,17–23]. In this series, the incidences of lymph node metastasis in intramucosal invasive gastric carcinomas and in submucosal invasive gastric carcinomas were .9% and 16.6%, respectively. In this analysis of a consecutive series of EGC cases from a single institution, we identified 4 independent predictive factors for lymph node metastases. Two of these were submocosal invasion and tumor diameter greater than 3.5 cm, which has also been reported as
T. Okabayashi et al. / The American Journal of Surgery 195 (2008) 229 –232
Fig. 3. A proposed patient management algorithm for patients with early gastric cancer.
a risk factor in previous studies [10,11]. In patients with EGC, there was a high correlation in the incidence of lymph node metastases between the size of the tumor and submucosal invasion (r ⫽ 1.00). This might be explained by the tendency of larger EGCs to invade the submucosal layer. In EGC with tumor size less than 1 cm in diameter, lymph node metastasis was not detected, regardless of the depth or histological classification. This may suggest a reduced metastatic capability of tumors smaller than 1 cm. Other parameters that we identified as risk factors for lymph node metastases included the presence of lymphatic permeation or vascular invasion. A close correlation has been demonstrated between histologically undifferentiated tumors and the incidence of lymph node metastasis in EGC [7,17,24,25]; however, our study did not reveal the histological type as an independent marker for lymph node metastasis after multivariate analysis. This result suggests that adenocarcinoma of the stomach at the early stage does not have greater lymphogenic or hematological malignant potential with lymph node metastatic capability regardless of histological classification including differentiated adenocarcinoma and undifferentiated adenocarcioma. The incidence of lymph node metastasis of EGC was 8.6% in this consecutive series of 440 gastrectomy cases from a single institution. Multivariate analysis comparing patients with and without lymph node metastasis identified 4 independent risk factors for lymph node metastasis: (1) submucosal invasive tumor; (2) tumor diameter greater than 3.5 cm; (3) the presence of vascular invasion; and (4) the presence of lymphatic permeation. Because surgical resection of the stomach may be associated with poorer outcome in terms of quality of life [26], we suggest a therapeutic pathway for the management of EGC that may reduce the need for larger surgical procedures in some patients (Fig. 3). Experienced endoscopists are able to accurately evaluate the extent of lesions in gastric carcinoma, and therefore, less invasive treatment, such as EMR or ESD, may become possible for EGC with tumors less than 3.5 cm in diameter [8 –15]. Because the exact tumor
231
diameter is not always easy to determine endoscopically, the endoscopic scale for measuring the size of the EGC and endoscopic ultrasonography might be useful [27]. EMR and ESD have become a reasonable and convenient diagnostic and treatment modality, because histological information about the whole tumor can be obtained and furthermore, a curative treatment is achieved in case of localized tumors without lymph node metastasis, preserving the whole stomach [28]. In recent years, EMR and/or ESD are a good and safe curative treatment option with feasible clinical outcomes in patients with EGC. We considered that EMR and/or ESD ensured an excellent prognosis, and should be the first choice of treatment in patients with EGC, although careful histological examination and long-term endoscopic surveillance are important [29,30]. However, when lymphatic permeation or vascular invasion is recognized in post-resection specimens, additional surgical resection of the stomach with lymphadenectomy would be recommended. Further prospective studies are warranted to evaluate the efficacy of this therapeutic strategy. In conclusion, patients with EGC with tumors of diameters less than 1 cm are probably the best candidates for endoscopic resection, whereas those with tumors greater than 3.5 cm should undergo gastrectomy with regional lymphadenectomy. For patients with tumor size between 1 cm and 3.5 cm we would recommend endoscopic resection initially, with a consideration for additional surgical resection if microscopic vascular invasion or lymphatic permeation was demonstrated. References [1] Huguier M, Ferro L, Barrier A. Early gastric carcinoma: spread and multicentricity. Gastric Cancer 2002;5:125– 8. [2] Seto Y, Shimoyama S, Kitayama J, et al. Lymph node metastasis and preoperative diagnosis of depth of invasion in early gastric cancer. Gastric Cancer 2001;4:34 – 8. [3] Okabayashi T, Gotoda T, Kondo H, et al. Usefulness of indigo carmine chromoendoscopy and endoscopic clipping for accurate preoperative assessment of proximal gastric cancer. Endoscopy 2000;32:S62. [4] Piso P, Werner U, Benten D, et al. Early gastric cancer— excellent prognosis after curative resection in 87 patients irrespective of submucosal infiltration, lymph-node metastases or tumor size. Langenbecks Arch Surg 2001;386:26 –33. [5] Popiela T, Kulig J, Kolodziejczyk P, et al. Long-term results of surgery for early gastric cancer. Br J Surg 2002;89:1035– 42. [6] Basili G, Nesi G, Barchielli A, et al. Pathologic features and longterm results in early gastric cancer: report of 116 cases 8 –13 years after surgery. World J Surg 2003;27:149 –52. [7] Borie F, Millat B, Fingerhut A, et al. Lymphatic involvement in early gastric cancer. Arch Surg 2000;135:1218 –23. [8] Shimada S, Yagi Y, Shiomori K, et al. Characterization of early gastric cancer and proposal of the optimal therapeutic strategy. Surgery 2001;129:714 –9. [9] Folli S, Margagni P, Roviello F, et al. Risk factors for lymph node metastases and their prognostic significance in early gastric cancer (EGC) for the Italian Research Group for Gastric Cancer (IRGGC). Jpn J Clin Oncol 2001;31:495–9. [10] Abe N, Mori T, Takeuchi H, et al. Laparoscopic lymph node dissection after endoscopic submucosal dissection: a novel and minimally invasive approach to treating early stage gastric cancer. Am J Surg 2005;190:496 –503. [11] Abe N, Watanabe T, Sugiyama M, et al. Endoscopic treatment or surgery for undifferentiated early gastric cancer? Am J Surg 2004; 188:181– 4. [12] Tsujitani S, Oka S, Saito H, et al. Less invasive surgery for early gastric cancer based on the low probability of lymph node metastasis. Surgery 1999;125:148 –54.
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