ABSTRACT: Despite mass population screening and an incidence of EGC in Japan that is at least double that of the West, there seem to be no genuine differences in the clinicopathological features of the disease between the two regions. The macroscopic appearance, size, depth of invasion, frequency of lymph node invasion, and histology of EGC are all remarkably similar in Japan, Europe and America, as are sex and age distributions. Patients with EGC are a number of years younger than those with advanced cancer. This is not surprising: Tsukuma et al followed 56 cases of EGC that were not surgically treated and estimated that the median "duration of EGC" before becoming advanced was 37 months. This suggests that EGC undergoes a period of slow growth before becoming advanced. Further differences between early and advanced cancers include a higher frequency of synchronous cancers and a longer symptom duration in EGC. Unfavourable prognostic factors in EGC include lymph node invasion, and invasion through the muscularis mucosae, though it is not clear whether these are independent. Repeated attempts have been made to identify other prognostic factors, but no clear pattern has emerged, with the possible exceptions of patient age, tumour size, and the presence of ulceration. The postsurgical outcome of EGC in the West is marginally less favourable than in Japan. In view of the similar clinical and pathological features in the two regions it seems likely, therefore, that this is because of the more aggressive surgical techniques traditionally used in Japan. Conversely, however, EMR has recently emerged as an important technique in Japan. Despite the advantages of low operative mortality and normal function of the postoperative stomach, there are also a number of potential disadvantages. It would seem sensible, therefore, to await the results of long term follow up studies before widespread adoption of EMR in Europe. Nevertheless, this technique should be considered for frail patients unfit for more radical surgery.
Project description:The presence of invasion is a diagnostic criterion of early gastric cancer (EGC) in Korea, whereas diagnosis in Japan is based on enlarged nuclei and prominent nucleoli. Moreover, the depth of invasion is the location of cancer cell infiltration in Korea, whereas it is the location of lymphovascular invasion (LVI) or cancer cell infiltration in Japan. We evaluated the characteristics of EGC with LVI to uncover the effects of different diagnostic criteria.Consecutive T1-stage EGC patients who underwent complete resection were included after endoscopic or surgical resection. The presence of LVI was evaluated.LVI was present in 112 of 1,089 T1-stage EGC patients. LVI was associated with depth of invasion (p<0.001) and age (p=0.017). The prevalence of LVI in mucosal cancer was significantly higher in Korea (p<0.001), whereas that of submucosal cancer was higher in Japan (p=0.024). For mucosal EGC types, LVI was positively correlated with diagnostic criteria applied in Korea (p=0.017). For submucosal EGC types, LVI was positively correlated with Japanese criteria (p=0.001) and old age (p=0.045).The higher prevalence of LVI for mucosal EGC in Korea and for submucosal EGC in Japan indicates that different diagnostic criteria should be considered when reading publications from other countries.
Project description:OBJECTIVES:To investigate the treatment effects of endoscopic submucosal dissection (ESD) versus endoscopic mucosal resection (EMR) for early gastric cancer (EGC). DESIGN:Meta-analysis. METHODS:We systematically searched three electronic databases, including PubMed, EmBase and the Cochrane library for studies published with inception to January 2018. The eligible studies should be evaluated for the efficacy and safety of ESD versus EMR for patients with EGC. The summary ORs and standard mean differences (SMDs) with 95% CIs were employed as effect estimates. Sensitivity analyses were conducted to evaluate the impact of single study on overall analysis. Subgroup analyses were performed for investigated outcomes to evaluate the treatment effects of ESD versus EMR for patients with EGC with specific subsets. RESULTS:Eighteen studies, with a total of 6723 patients with EGC, were included in final analysis. The summary ORs indicated that patients with EGC who received ESD were associated with an increased incidence of en bloc resection (OR: 9.00; 95%?CI: 6.66 to 12.17; p<0.001), complete resection (OR: 8.43; 95%?CI: 5.04 to 14.09; p<0.001) and curative resection (OR: 2.92; 95%?CI: 1.85 to 4.61; p<0.001) when compared with EMR. Furthermore, ESD was associated with lower risk of local recurrence (OR: 0.18; 95%?CI: 0.09 to 0.34; p<0.001). In addition, there was no significant difference between ESD and EMR for the risk of bleeding (OR: 1.26; 95%?CI: 0.88 to 1.80; p=0.203). Though, ESD was correlated with greater risk of perforation (OR: 2.55; 95%?CI: 1.48 to 4.39; p=0.001), and longer operation time (SMD: 1.12; 95%?CI: 0.13 to 2.10; p=0.026) as compared with EMR. Additionally, several different features observed in included studies and patients could bias the effectiveness of ESD versus EMR in patients with EGC. CONCLUSIONS:ESD is superior than EMR for en bloc resection, complete resection, curative resection and local recurrence, while it increased perforation risk and longer operation time.
Project description:The consensus of endoscopic therapy for early gastric cancer (EGC) mainly depends on its clinicopathological features. However, the roles of tumor-associated neutrophils (TANs) in EGC remain uncertain. Here, we explored its predictive role for lymph node metastasis (LNM) in EGC. Three hundred twenty-two patients who underwent radical gastrectomy for EGC were enrolled. Preoperative peripheral blood was used to analyze the neutrophil-to-lymphocyte ratio (NLR), and the different status of TANs was determined by hematoxylin-and-eosin staining (H&E) and immunohistochemistry (IHC). TANs, rather than NLR, were positively associated with tumor size, Lauren classification, lymphovascular invasion (LVI), and LNM. Univariate analysis revealed that TANs were associated with LNM as well as tumor size, depth of invasion, Lauren classification, histological classification, LVI, and perineural invasion. In addition to histological classification and LVI, TANs were found to be an independent risk factor for LNM in EGC (P = 0.013). Stratification analysis by depth of invasion showed LVI in SM1 tumor, and both LVI and TANs (P = 0.042) in SM2 tumor were independent risk factors for LNM. In conclusion, TANs in EGC can predict LNM, and TANs may help to estimate LNM precisely in addition to the current criteria.
Project description:The presence of ulcer in early gastric cancer (EGC) is important for the feasibility of endoscopic resection, only a few studies have examined the clinicopathological implications of endoscopic ulcer in EGC.To determine the role of endoscopic ulcer as a predictor of clinical behaviors in EGC.Data of 3,270 patients with EGC who underwent surgery between January 2005 and December 2012 were reviewed. Clinicopathological characteristics were analyzed in relation to the presence and stage of ulcer in EGC. Based on endoscopic findings, the stage of ulcer was categorized as active, healing, or scar. Logistic regression analysis was performed to analyze factors associated with lymph node metastasis (LNM).2,343 (71.7%) patients had endoscopic findings of ulceration in EGC. Submucosal (SM) invasion, LNM, lymphovascular invasion (LVI), perineural invasion, and undifferentiated-type histology were significantly higher in ulcerative than non-ulcerative EGC. Comparison across different stages of ulcer revealed that SM invasion, LNM, and LVI were significantly associated with the active stage, and that these features exhibited significant stage-based differences, being most common at the active stage, and least common at the scar stage. The presence of endoscopic ulcer and active status of the ulcer were identified as independent risk factors for LNM.Ulcerative EGC detected by endoscopy exhibited more aggressive behaviors than non-ulcerative EGC. Additionally, the endoscopic stage of ulcer may predict the clinicopathological behaviors of EGC. Therefore, the appearance of ulcers should be carefully evaluated to determine an adequate treatment strategy for EGC.
Project description:MicroRNAs (miRNAs) play a critical role in gastric cancer progression and metastasis. This study investigated the role of miRNA-135a in early gastric cancer (EGC) including lymph node (LN) metastasis. We examined the correlation between miRNA-135a expression and clinical outcomes in 59 patients who underwent surgery for EGC. Using gastric cancer cell lines, we performed functional and target gene analyses. miRNA-135a expression was down-regulated in 33.9% of patients. These patients showed a significantly more advanced stage (TNM stage ? IB, 35.0% vs. 12.8%, p?=?0.045) and higher rate of LN metastasis (30.0% vs. 5.1%, p?=?0.014) than those with up-regulation of miRNA-135a expression. In a multivariate analysis, down-regulation of miRNA-135a was an independent risk factor for LN metastasis (adjusted odds ratio, 8.04; 95% confidence interval, 1.08-59.81; p?=?0.042). Functional analyses using gastric cancer cell lines showed that miRNA-135a suppressed cell viability, epithelial-mesenchymal transition, cell invasion, and migration. ROCK1 was a target of miRNA-135a and its expression was inversely correlated to that of miRNA-135a. ROCK1 expression was significantly increased in EGC patients with LN metastasis than in those without LN metastasis. Our results confirm the tumor-suppressive role of miRNA-135a, and demonstrate its role in LN metastasis in EGC. miRNA-135a and its target gene ROCK1 may be novel therapeutic and prognostic targets for EGC.
Project description:This study evaluated the possibility of endoscopic submucosal dissection (ESD) for early gastric cancer with papillary adenocarcinoma (EGC-PAC). PAC, an uncommon pathologic type of stomach cancer, is classified into differentiated-type histology. However, aggressive features, including a high rate of submucosal invasion, lymphovascular invasion (LVI), and lymph node metastasis (LNM), have been reported in studies with surgical specimens. Treatment outcomes of ESD for EGC-PAC have not been precisely demonstrated. Core databases were sought for the following inclusion criteria: studies of endoscopic resection or surgery of EGC-PAC presenting the following therapeutic indicators; en bloc resection, complete resection, curative resection, recurrence, complications associated with procedures, LVI, or LNM that enabled an analysis of ESD possibility. Overall, 15 studies were included for systematic review. Frequent submucosal invasion and high LVI were noted in EGC-PAC. However, PAC was not significantly associated with LNM. Pooled en bloc resection, complete resection, and curative resection rates were 89.7% (95% confidence interval: 55.3%-98.4%), 85.3% (67.7%-94.2%), and 67% (43%-84.5%), respectively. No LNM was observed if EGC-PAC satisfied the curative resection criteria. ESD seems technically feasible, although a high LVI rate results in a lower rate of curative resection.
Project description:Lymph node status is crucial to determining treatment for early gastric cancer (EGC). We aim to establish a nomogram to predict the possibility of lymph node metastasis (LNM) in EGC patients.Medical records of 952 EGC patients with curative resection, from 2002 to 2014, were retrospectively retrieved. Univariate and multivariate analysis were performed to examine risk factors associated with LNM. A nomogram for predicting LNM was established and internally validated.Five variables significantly associated with LNM were included in our model, these are sex (Odd ratio [OR] = 1.961, 95% confidence index [CI], 1.334 to 2.883; P = 0.001), depth of tumor (OR = 2.875, 95% CI, 1.872 to 4.414; P = 0.000), tumor size (OR = 1.986, 95% CI, 1.265 to 3.118; P = 0.003), histology type (OR = 2.926, 95% CI, 1.854 to 4.617; P = 0.000) and lymphovascular invasion (OR = 4.967, 95% CI, 2.996 to 8.235; P = 0.000). The discrimination of the prediction model was 0.786.A nomogram for predicting lymph node metastasis in patients with early gastric cancer was successfully established, which was superior to the absolute endoscopic submucosal dissection (ESD) indication in terms of the clinical performance.
Project description:BACKGROUND:Most lymph node metastasis (LNM) models for early gastric cancer (EGC) include lymphovascular invasion (LVI) as a predictor. However, LVI must be confirmed by postoperative pathology. In this study, we aimed to develop a model for predicting the risk of LNM/LVI in EGC using preoperative factors. METHODS:EGC patients who underwent radical gastrectomy at Fujian Medical University Union Hospital and Sun Yat-sen University Cancer Center (n?=?1460) were selected as the training set. The risk factors of LNM/LVI were investigated. Data from the International study group on Minimally Invasive surgery for GASTRIc Cancer trial (n?=?172) were selected as the validation set. RESULTS:In the training set, the incidence of LNM/LVI was 21.6%. The 5-year cancer-specific survival rates of patients with and without LNM/LVI were 92.4 and 95.0%, respectively, with significant difference (P?=?0.030). Multivariable logistic regression analysis showed that the four independent risk factors for LNM/LVI were female, tumor larger than 20?mm, submucosal invasion and undifferentiated tumor histological type (all P?<? 0.05); the area under the curve (AUC) was 0.694 (95% confidence interval [CI]: 0.659-0.730). Patients were divided into low-risk, intermediate-risk, high-risk and extremely high-risk groups by recursive partitioning analysis; the incidences of LNM/LVI were 5.4, 12.6, 24.2 and 37.8%, respectively (P?<? 0.001). The AUC of the validation set was 0.796 (95%CI, 0.662-0.851) and the predictive performance of the LNM/LVI risk in the validation set was consistent with that in the training set. CONCLUSIONS:The risk of LNM/LVI in differentiated mucosal EGC is low, which indicated that endoscopic resection is a treatment option. The risk of LNM/LVI in undifferentiated mucosal EGC and submucosa EGC are high and gastrectomy with lymph node dissection is suggested.
Project description:Previous studies reported substantial differences between proximal and distal gastric cancer, however, most of the cases included in these studies were advanced gastric cancers (AGCs). The aim of this study was to investigate the unique characteristics of proximal early gastric cancer (EGC) by comparing with distal EGC. From March 2007 to March 2016, proximal and distal EGC patients who underwent endoscopic or surgical resection at our institution were matched 1:3 according to age and sex. We retrospectively analyzed the clinical and histopathological information. A total of 368 patients were enrolled including 92 (25%) in the proximal and 276 (75%) in the distal group. The proportion of patients who underwent surgery (56.5 vs. 20.3%, p<0.001), undifferentiated type (38.0 vs. 19.6%, p<0.001), tumor size (29.5 ±19.4 vs. 20.3 ±16.8 mm, p<0.001) and submucosal (SM) invasion (60.9 vs. 25.7%, p<0.001) were significantly higher in the proximal group than in the distal group. In multivariate analysis, the proximal location of EGC was a significant risk factor for SM invasion in the total population (odds ratio [OR], 3.541; 95% confidence interval [CI], 2.053-6.110; p<0.001), and in subgroup with EGC < 30mm (n = 279) (OR, 5.940; 95% CI, 2.974-11.862; p<0.001). In conclusion, careful therapeutic decision of proximal EGC is essential due to the different histopathological characteristics such as large tumor size and higher potential for SM invasion.
Project description:Endoscopic surgery is increasingly used for early gastric cancer (EGC) treatment worldwide, and lymph node metastasis remains the most important risk factor for endoscopic surgery in EGC patients. Olfactomedin 4 (OLFM4) is mainly expressed in the digestive system and upregulated in several types of tumors. However, the role of OLFM4 in EGC has not been explored. We evaluated OLFM4 expression by immunohistochemical staining in 105 patients with EGC who underwent gastrectomy. The clinicopathological factors and OLFM4 expression were co-analyzed to predict lymph node metastasis in EGC. The metastatic mechanism of OLFM4 in gastric cancer was also investigated. We found that OLFM4 was upregulated in EGC tumor sections, and relatively low expression of OLFM4 was observed in patients with lymph node metastasis. OLFM4 expression as well as tumor size and differentiation were identified as independent factors, which could be co-analyzed to generate a better model for predicting lymph node metastasis in EGC patients. In vitro studies revealed that knockdown of OLFM4 promoted the migration of gastric cancer cells through activating the NF-?B/interleukin-8 axis. Negative correlation between OLFM4 and interleukin-8 expression was also observed in EGC tumor samples. Our study implies that OLFM4 expression is a potential predictor of lymph node metastasis in EGC, and combing OLFM4 with tumor size and differentiation could better stratify EGC patients with different risks of lymph node metastasis.