Early Gastric Cancer Metastasis Research Articles

Predictable Factors for Lymph Node Metastasis in Early Gastric Cancer—Analysis of Single Institutional Experience

IntroductionPrediction of lymph node metastasis in early gastric cancer (EGC) is very important to decide treatment strategies preoperatively. The aim of this study was to evaluate factors that predict the presence of lymph node metastasis and to indentify the differences between mucosal and submucosal gastric cancers. MethodsA total of 376 patients with EGC who underwent gastrectomy from March 1999 through December 2007 were retrospectively identified. The clinopathological factors and biological markers (p53, Ki67) were analyzed. ResultsThe rate of lymph node metastasis was 9.6% (mucosal cancer 2.8%, submucosal cancer 18.4%). Tumor size, depth of invasion, macroscopic type, and lymphovascular invasion were related to lymph node metastasis in EGC. When the carcinomas were confined to the mucosal layer, tumor size and lymphovascular invasion showed significant correlation with lymph node metastasis. On the other side, macroscopic type and lymphovascular invasion were association with lymph node metastasis in submucosal carcinoma. ConclusionThe risk factors for lymph node metastasis in EGC are quite different depending on depth of tumor invasion. To predict lymph node metastasis in EGC, it is recommended that distinct assessment according to individual situation should be clearly established.

Genomic Profiling of Submucosal-Invasive Gastric Cancer by Array-Based Comparative Genomic Hybridization

Genomic copy number aberrations (CNAs) in gastric cancer have already been extensively characterized by array comparative genomic hybridization (array CGH) analysis. However, involvement of genomic CNAs in the process of submucosal invasion and lymph node metastasis in early gastric cancer is still poorly understood. In this study, to address this issue, we collected a total of 59 tumor samples from 27 patients with submucosal-invasive gastric cancers (SMGC), analyzed their genomic profiles by array CGH, and compared them between paired samples of mucosal (MU) and submucosal (SM) invasion (23 pairs), and SM invasion and lymph node (LN) metastasis (9 pairs). Initially, we hypothesized that acquisition of specific CNA(s) is important for these processes. However, we observed no significant difference in the number of genomic CNAs between paired MU and SM, and between paired SM and LN. Furthermore, we were unable to find any CNAs specifically associated with SM invasion or LN metastasis. Among the 23 cases analyzed, 15 had some similar pattern of genomic profiling between SM and MU. Interestingly, 13 of the 15 cases also showed some differences in genomic profiles. These results suggest that the majority of SMGCs are composed of heterogeneous subpopulations derived from the same clonal origin. Comparison of genomic CNAs between SMGCs with and without LN metastasis revealed that gain of 11q13, 11q14, 11q22, 14q32 and amplification of 17q21 were more frequent in metastatic SMGCs, suggesting that these CNAs are related to LN metastasis of early gastric cancer. In conclusion, our data suggest that generation of genetically distinct subclones, rather than acquisition of specific CNA at MU, is integral to the process of submucosal invasion, and that subclones that acquire gain of 11q13, 11q14, 11q22, 14q32 or amplification of 17q21 are likely to become metastatic.

Overt bone metastasis and bone marrow micrometastasis of early gastric cancer

Recently we encountered two cases of early gastric cancer (EGC) with bone metastasis after surgery. As they were not accompanied by overt liver, lung, or peritoneal metastasis, we examined the clinical significance of bone metastasis in EGC and its mechanisms by a review of the literature. We found only 10 cases of EGC complicated with overt bone metastasis in the English literature, so we also examined the Japanese reports of such cases. The main histologic type of cases of bone metastasis from EGC was the diffuse type, and there were long intervals between surgery and overt bone metastasis. One reason for such long intervals may have been the tumor dormancy. Two types of dormancy, dynamic and static, and two types of postoperative overt metastases, that of micrometastatic origin (normograde metastatic process) and that of bone marrow origin (retrograde metastatic process), were considered. We speculated that there may be specific routes by which the cancer cells infiltrate the bone marrow directly from EGC or lymph node metastasis. The procedures for diagnosing bone micrometastasis using monoclonal antibodies have recently been improved, but their accuracy rates are still not universally accepted. New, more reliable examinations are required to improve the survival rates of EGC.

Matrix Metalloproteinase 7 (MMP-7) Expression Predicts the Status of Lymph Node Metastasis in Early Gastric Cancer

Purpose: Accurate prediction of lymph node (LN) status is of crucial importance for appropriate treatment planning in early gastric cancer (EGC). Matrix metalloproteinases (MMPs) have been shown to be involved in the pathogenesis of tumor progression and metastasis in gastric carcinoma. In this study, we investigated the association between MMPs expressions and LN metastasis in EGC. Methods: Thirty-four LN positive and 80 LN negative pT1 tumors were immunohistochemically analyzed for MMP-2, MMP-7, and MMP-9 expression. The relation of MMPs expressions to LN metastasis was analyzed in the univariate and multivariate model. Results: There were 73 men and 41 women with a mean age of 60 years. Among the pathologic characteristics, larger tumor size, submucosal invasion and lymphatic invasion were factors that are significantly associated with LN metastasis in pT1 tumors. Immunohistochemistry showed significantly higher MMP-7 expression (82.4% vs. 54.4%, P=0.005) in LN positive tumors, whereas MMP-9 (85.3% in LN positive vs. 67.5% in LN negative) and MMP-2 (70.6% in LN positive vs. 57.5% in LN negative) expression did not reach statistical significance. Multivariate analysis revealed that MMP-7 expression (OR 4.915, 95% CI 1.375∼17.573) is an independent predictor of LN metastasis in EGCs, along with lymphatic invasion by tumor cells (OR 10.337, 95% CI 2.785∼38.360). Conclusion: Our study shows that MMP-7 expression is significantly associated with LN metastasis in EGC. MMP-7 expression can be used to predict LN status in EGCs in addition to other pathological parameters.

Predictive factors associated with lymph node metastasis in early gastric cancer with submucosal invasion: an analysis of 290 cases

Predictive factors associated with lymph node metastasis in early gastric cancer with submucosal invasion: an analysis of 290 cases

Predictive factors for lymph node metastasis in early gastric cancer

To analyze the predictive factors for lymph node metastasis (LNM) in early gastric cancer (EGC). Data from patients surgically treated for gastric cancers between January 1994 and December 2007 were retrospectively collected. Clinicopathological factors were analyzed to identify predictive factors for LNM. Of the 2936 patients who underwent gastrectomy and lymph node dissection, 556 were diagnosed with EGC and included in this study. Among these, 4.1% of patients had mucosal tumors (T1a) with LNM while 24.3% of patients had submucosal tumors with LNM. Univariate analysis found that female gender, tumors ≥ 2 cm, tumor invasion to the submucosa, vascular and lymphatic involvement were significantly associated with a higher rate of LNM. On multivariate analysis, tumor size, lymphatic involvement, and tumor with submucosal invasion were associated with LNM. Tumor with submucosal invasion, size ≥ 2 cm, and presence of lymphatic involvement are predictive factors for LNM in EGC.

The Extended Indications of Endoscopic Submucosal Dissection (ESD) for Early Gastric Cancer Are Thus Not Entirely Safe

Early gastric cancer (EGC) is defined as tumor invasion confined to the mucosa or submucosa, regardless of the presence of regional lymph node metastasis. Lymph node metastasis is the most powerful and important prognostic factor for gastric cancer. Based on the risk of lymph node metastasis in EGC obtained from a large number of surgical cases in Japan, it was suggested that the criteria for endoscopic mucosal resection (EMR) and endoscopic submucosal resection (ESD) as local treatment for EGC might be extended. However, extending the indications for EMR and ESD remains controversial because the long-term outcomes of these procedures have not been fully documented, and there is a risk for lymph node metastasis. Furthermore, current diagnostic imaging techniques are unsatisfactory for accurately predicting metastasis to lymph nodes. Moreover, the long-term results of standard radical gastrectomy including minimally invasive procedures for stage IA have been increasing and have reached 99 to 100%. To determine the true efficacy of endoscopic resection of EGC, we need more evidence of long-term follow-up, standardization of techniques, and pathological interpretation.

Management of endoscopic submucosal dissection complications

Endoscopic submucosal dissection (ESD) is a new promising technique that allows endoscopic en bloc resection of premalignant and early malignant lesions in the gastrointestinal tract. In contrast to conventional endoscopic mucosal resection (EMR), lesions can be resected en bloc irrespective of their size. Clear advantages are an improvement in histopathological assessment of R0 resections and a lower risk of recurrence. Large series from Japan have shown significant improvement of en bloc resections after ESD compared with EMR in early gastric cancers [1], colonic lesions [2], and early esophageal neoplasms [3]. Guideline criteria for the resection of early gastric cancers in the pre-ESD era restricted the lesion size to 20 mm or less for conventional EMR [4]. New data on the risk of lymph node metastasis in early gastric cancer and the new ESD technique have allowed an extension of the resection criteria [5] [6]; for differentiated intramucosal cancers, the restriction on size could be lifted completely.

Characteristics of lymph node metastasis and prognostic analysis in 157 early gastric cancer patients

To explore the pattern of lymph node metastasis and its influence on the prognosis of early gastric cancer(EGC). The pattern of lymph node metastasis and the 3-,5-year survival rates in 157 EGC patients undergone surgery from October 1995 to October 2005 were analyzed retrospectively. The SPSS 11.5 statistics software was used to perform univariate and multivariate analysis. Twenty-two cases had lymph node metastasis among 157 EGC patients(14%). Two mucous cancers(2.4%) and 20 submucosal tumors(27.0%) had lymph node metastases (P<0.01). Lymph node metastasis was not seen in minute gastric cancer(diameter < or =0.5 cm). Lymph node metastasis rates were 6.4% in the cancers with diameter 1.1-2.0 cm and 21.5% in the cancers with the diameter >2.0 cm(P<0.01). Besides, lymph node metastasis rate of well-differentiated EGC was 0, of moderate differentiated EGC 11.1%, and poor-differentiated EGC 0.9%(P<0.01). Of 9 cases with vascular cancer embolus, 4 had lymph node metastases. Logistic regression analysis showed that tumor size, vascular cancer embolus, histopathological type and depth of invasion were independent factors of lymph node metastasis in EGC. The 3- and 5-year survival rates of EGC patients with lymph node metastasis were 81.6 % and 79.5% respectively, which were much lower than those without lymph node metastasis(95.7% and 93.2%, P<0.01). Lymph node metastasis in EGC is mainly correlated with depth of infiltration, tumor size, vascular cancer embolus and differentiation. For EGC treatment, choice should be made reasonably based on the risk of lymph node metastasis.

Clinical Significance of Splenic Hilar Lymph Node Metastasis in Proximal Gastric Cancer

Prophylactic splenectomy for splenic hilar node removal is generally not advised because of the high morbidity and mortality rates and the uncertain impact on patient survival. The aim of this study was to compare the clinicopathologic characteristics and effect on survival of the following two groups: the splenic hilar lymph node metastasis group and the non-metastasis group. Three hundred and nineteen patients with proximal gastric adenocarcinoma who underwent curative total gastrectomy with simultaneous splenectomy and D2 lymph node dissection at the Samsung Medical Center between 1995 and 2004 were analyzed retrospectively. Forty one patients (12.9%) had splenic hilar node metastasis. The splenic hilar metastasis group was shown to have a higher proportion of females (48.8%), Borrmann type IV (34.1%), tumor size >5 cm (82.9%), poorly differentiated adenocarcinoma (51.2%), signet ring cell carcinoma (31.7%), Lauren diffuse-type (80.5%), endolymphatic invasion (65.5%), and nerve invasion (46.4%; p < 0.05). There was no splenic hilar node metastasis in early gastric cancer. The 5-year survival rate was 11.04% for the hilar node metastasis group (p < 0.001), which was significantly lower than in the non-metastasis group, in which it was 51.57%. Multivariate analysis revealed that hilar node metastasis was an independent prognostic factor [hazard ratio 1.671; 95% confidence interval (CI) 1.075-2.595; p = 0.022]. Splenic hilar node metastasis was not apparent in early gastric cancer and had a very poor prognosis, even though curative resection was done, so the effectiveness of prophylactic splenectomy is uncertain.

Endoscopic Resection of Undifferentiated Early Gastric Cancer

Endoscopic resection is one of the curative options for early gastric cancer. However, based on large-scale data about the risk of lymph node metastasis in early gastric cancer, endoscopic resection has been attempted for the following: differentiated intramucosal gastric cancer, regardless of size and without ulcers; differentiated intramucosal cancer, 30 mm in size with ulcers; minute submucosal differentiated cancer

Clinical Significance of VEGF-C and COX-2 Expression in Gastric Carcinoma with Submucosal Invasion

Purpose: Lymph node metastasis is an important factor in determining prognosis and therapeutic options for early gastric cancer (EGC) patients. Vascular endothelial growth factor (VEGF)-C and D are known as lymphangiogenic factors, and cyclooxygenase (COX)-2 is thought to play a role in lymph node metastasis in gastric carcinoma. This study was designed to determine whether the expression of VEGF-C, VEGF-D, and COX-2 is associated with clinicopathologic factors, especially lymph node metastasis in EGCs invading the submucosa. Materials and Methods: Tissue samples were obtained from 85 Patients undergoing standard gastrectomy with lymph node dissection between 1991 and 2007 in the Department of Surgery of Daejeon St. Mary's Hospital in Daejeon, Korea. All patients were diagnosed with gastric cancers and submucosal invasion. We examined the expression of VEGF-C, VEGF-D, and COX-2 using immunohistochemical methods. Results: Of the 85 patients, 16 (18.8%) had lymph node metastasis. VEGF-C, VEGF-D, and COX-2 were positively expressed in 34.1% (29/85), 22.3% (19/85), and 37.6% (32/85) of the patients. VEGF-C and COX-2 expression was significantly correlated with lymph node metastasis (P

Clinicopathological Features Associated with Lymph Node Metastasis in Early Gastric Cancer: Analysis of a Single-Institution Experience in China

An accurate assessment of potential lymph node metastasis is an important issue for the appropriate treatment of early gastric cancer. Minimizing the number of invasive procedures used in cancer therapy is critical for improving the patient's quality of life. To evaluate the clinicopathological features associated with lymph node metastasis of early gastric cancer in patients from a single institution in China. A retrospective review of data from 410 patients surgically treated for early gastric cancer at the First Affiliated Hospital (Nanjing, China) between 1998 and 2007, was conducted. The clinicopathological variables associated with lymph node metastasis were evaluated. Lymph node metastasis was observed in 12.20% of patients. The macroscopic type, tumour size, location in the stomach, depth of gastric carcinoma infiltration, and presence of vascular or lymphatic invasion showed a positive correlation with the incidence of lymph node metastasis by univariate analysis. Multivariate analyses revealed histological classification, macroscopic type, tumour size, depth of gastric carcinoma infiltration, and the presence of vascular or lymphatic invasion to be significantly and independently related to lymph node metastasis. The depth of gastric carcinoma infiltration was the strongest predictive factor for lymph node metastasis. For intramucosal cancer, tumour size was the unique risk factor for lymph node metastasis. For submucosal cancer, histological classification and tumour size were independent risk factors for lymph node metastasis. Histological classification, macroscopic type, tumour size, depth of gastric carcinoma infiltration, and the presence of vascular or lymphatic invasion are independent risk factors for lymph node metastasis in patients with early gastric cancer in China. Minimal invasive treatment, such as endoscopic mucosal resection, may be possible for highly selected cancers.

Histopathological predictor for regional lymph node metastasis in gastric cancer

Regional lymph node metastasis in gastric cancer is a definitive indicator of the patient's prognosis. The goal of this study was to identify the predictors for lymph node metastasis among all the possible histopathological parameters, especially by conducting an objective discrimination of the lymphatic and blood vessels. A total of 210 resected primary gastric cancers with or without lymph node metastasis were evaluated based on the conventional histopathological parameters together with immunohistochemistry using antisera-recognizing lymphatic endothelial hyaluronan receptor-1 (LYVE-1), von Willebrand factor, and lymphangiogenesis promoter vascular endothelial growth factor-C (VEGF-C) antibodies. A multivariate regression analyses of the results indicated that only lymphatic invasion was a significant independent predictor of lymph node metastasis at any stage of cancer invasion. VEGF-C expression was partially related to lymph node metastasis in early gastric cancer. The identification of lymphatic invasion by LYVE-1 antibody is therefore useful to predict regional lymph node metastasis in gastric cancer.

Predicting lymph node status in early gastric cancer

Accurate prediction of lymph node (LN) status is of crucial importance for appropriate treatment planning in patients with early gastric cancer (EGC). However, there is no definitive consensus yet on which patient and/or tumor characteristics are associated with LN metastasis. A systematic search for studies investigating the relationship between patient and/or tumor characteristics and LN metastasis in EGC was performed in PubMed/MEDLINE. Patient and/or tumor characteristics associated with LN metastasis were identified by meta-analyzing results of individual studies. Forty-five studies were included. Variables significantly associated with LN metastasis in gastric cancer limited to the mucosa were: age younger than 57 years, tumor location in the middle part of the stomach, larger tumor size, macroscopically depressed tumor type, tumor ulcerations, undifferentiated tumors, diffuse tumor type according to the Lauren classification, lymphatic tumor invasion, tumors with a proliferating cell nuclear antigen (PCNA) labeling index of more than 25%, and matrix metalloproteinase-9-positive tumors. Variables significantly associated with LN metastasis in gastric cancer limited to the submucosa were: female sex, tumor location in the lower part of the stomach, larger tumor size, undifferentiated tumors, increasing depth of submucosal invasion, lymphatic tumor invasion, vascular tumor invasion, increased submucosal vascularity, tumors with a PCNA labeling index of more than 25%, tumors with a gastric mucin phenotype, and vascular endothelial growth factor-C-positive tumors. We identified several variables associated with LN metastasis in EGC. These variables should be included in future research, in order to assess which of these variables remain as significant predictors of LN metastasis.

Preliminary experiences of application of sentinel lymph node navigation technique in early gastric cancer

To investigate the feasibility and clinical significance of sentinel lymph node (SLN) navigation limited surgery in early gastric cancer (EGC). Thirty-nine patients confirmed with EGC between January 2002 and December 2006 were randomly divided into tailored surgery group (20 cases) and conventional surgery group (19 cases). By combining the mapping agents of (99m)Tc labeled sulfur colloid solution and blue violet, SLN biopsy was conducted in tailored surgery group, in which a limited gastric resection with D0-D1 lymphadenectomy was performed in 17 cases with negative SLN examined by routine HE staining during operation; standard radical gastrectomy with lymphadenectomy (D2) was conducted in the other 3 cases with positive SLN and in all the cases of conventional surgery group. The diagnostic accuracy and false-negative rate of SLN status were calculated respectively. The operation outcome and postoperative complication and survival rate were compared between the two groups. SLNs were detected in all 20 patients with a successful detection rate of 100% in tailored surgery group. The number of detected SLNs ranged from 1 to 3, with a mean of 2.2 per case. The diagnostic accuracy and false-negative rate was 95% and 5%, respectively. The hospital stay and recovery time of gastrointestinal functions in patients undergoing limited surgery were significantly shorter than in conventional surgery group and with similar postoperative survival and less complications. SLN biopsy may provide an accurate diagnostic procedure for detecting lymph node metastasis in EGC. Patients with node-negative EGC receiving limited surgery are likely to benefit from minimally invasive approach with the similar survival as standard radical surgery.

Predictive Factors for Lymph Node Metastasis in Early Gastric Cancer With Submucosal Invasion

An accurate assessment of a potential lymph node metastasis is an important issue for the appropriate treatment of early gastric cancer. Minimizing the amount of invasive procedures used in cancer treatment is critical for improving the patient's quality of life. Therefore, this study analyzed the predictive risk factors for a lymph node metastasis in early gastric cancer with a submucosal invasion. The data from 1043 patients surgically treated for early gastric cancer with submucosal invasion between 2002 and 2005 were reviewed retrospectively. The patients were divided into 3 layers according to their depth: SM1, SM2, and SM3. The clinicopathological variables predicting a lymph node metastasis were evaluated. A lymph node metastasis was observed in 19.4% of patients. The tumor size, histologic type, Lauren classification, tumor depth, and perineural invasion showed a positive correlation with the rate of lymph node metastasis and N category by univariate analysis. Multivariate analyses revealed the tumor size (>or=2 cm) and lymphatic involvement to be significantly and independently related to lymph node metastasis. The presence of lymphatic involvement was the strongest predictive factor for a lymph node metastasis, being observed in 43.8% of cases in which a lymph node metastasis had been revealed. No lymph node metastasis was observed in the 12 cases with no lymphatic involvement, SM1 invasion, and tumor size <1 cm. Lymphatic involvement and tumor size are independent risk factors for a lymph node metastasis in early gastric cancer with submucosal invasion. Minimal invasive treatment, such as endoscopic mucosal resection, may be possible in highly selective submucosal cancers with no lymphatic involvement, SM1 invasion, and tumor size <1 cm.

Relationship between preoperative clinicopathologic characteristics and lymph node metastasis in early gastric cancer

Objective To investigate the features of the preoperative clinicopathologic characteristics in correlation with lymph node metastasis.

Analysis of Clinicopathological Factors Associated with Lymph Node Metastasis in Early Gastric Cancer

Analysis of Clinicopathological Factors Associated with Lymph Node Metastasis in Early Gastric Cancer

Significance of Lymphatic Invasion on Regional Lymph Node Metastasis in Early Gastric Cancer Using LYVE-1 Immunohistochemical Analysis

It has been reported that lymphatic invasion is a predictor for lymph node metastasis in early gastric cancer (EGC); however, it has been impossible to differentiate between lymphatic invasion and blood vessel invasion using current staining techniques. We studied the significance of lymphatic invasion on regional lymph node metastasis in EGC by using human lymphatic vessel endothelial hyaluronan receptor-1 (LYVE-1) antibody, specific to lymphatic vessels, and von Willebrand factor (vWF) antibody, specific to the blood vessels, to clearly distinguish these vascular tissues. EGC tissues were obtained from 66 node-positive and 66 node-negative subjects and were matched by age and sex. These tissues were immunostained with antibodies against LYVE-1 and vWF. Multivariate logistic regression analysis demonstrated that lymphatic invasion was a significant independent predictor for regional lymph node metastasis (odds ratio, 4.667; P = .0094), whereas blood vessel invasion was not. Thus, lymphatic invasion identified by LYVE-1 antibody could predict the existence of regional lymph node metastasis in EGC.