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ABSTRACT: We investigated the clinical and pathological features as well as the prognosis of signet ring cell carcinoma (SRC) and gastric mucinous carcinoma (GMC) to lay a foundation for the management of these two diseases. Two thousand four hundred thirty gastric cancer patients, including 288 SRCs and 80 GMCs who had received a gastrectomy between 1997 and 2007, were retrospectively evaluated. There were significant differences in tumor location, distant metastasis status, lymph node dissection, depth of invasion, Borrmann type, pTNM stage, and pathological lymph node status between SRCs and GMC (P = 0.001, 0.003, 0.01, 0.0002, 0.0013, 0.0001, and 0.265, respectively). After prognostic analysis, the cases with GMC received a relatively low 5-year specific survival rate compared to SRC (58.68 % vs. 66.25 %; P = 0.064). After Cox regression analysis, gender, age, lymph node metastatic ratio, pTNM stage, curative operation, and distant metastasis were identified as the independent prognostic factors in SRC. On the other hand, pTNM stage and distant metastasis were identified as the independent prognostic factors in GMC. In conclusion, the clinical and pathological features as well as prognosis of GMC and gastric SRC differed. Therefore, the treatment of the two diseases should be individualized.
Tumor Biology 05/2013; · 1.94 Impact Factor
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ABSTRACT: The prognostic significance of tumor size in gastric cancer is not well defined. The objective of this study was to identify the prognostic value of tumor size in patients with gastric cancer.
We retrospectively reviewed a total of 1800 patients with gastric cancer admitted to our hospital between 1997 and 2007. These patients were divided into two groups according to tumor size: small size group (SSG, tumor ≤5 cm) and large size group (LSG, tumor >5 cm). We compared clinico-pathologic features of the two groups and investigated the prognostic factors by performing univariate, multivariate, and stage- stratified analyses according to tumor size.
LSG had more aggressive clinico-pathologic features than SSG. Tumor size was an independent prognostic indicator in patients with gastric cancer. In a stratified-pT, pN, and pTNM analysis, survival of patients with LSG was significantly worse than that of patients with SSG and advanced stage. Tumor size was not a significant predictor of survival in patients with early stage tumors. Large tumor size was associated with shorter survival in patients with stages N0, N1, N2, and N3, and stages I, II, III, and IV.
Tumor size is a simple and practical prognostic factor in patients with gastric cancer. Tumor size could supplement clinical staging in the future.
PLoS ONE 01/2013; 8(1):e54502. · 4.09 Impact Factor
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Jingcui Yu,
Peng Liu,
Xiaobo Cui,
Yu Sui,
Guohua Ji,
Rongwei Guan,
Donglin Sun,
Wei Ji,
Fangli Liu,
An Liu,
Yuzhen Zhao,
Yang Yu,
Yan Jin,
Jing Bai,
Jingshu Geng, Yingwei Xue,
Jiping Qi,
Ki-Young Lee,
Songbin Fu
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ABSTRACT: Previously, we identified 3 overlapping regions showing loss of heterozygosity (LOH, R(1)-R(3) from 11 to 30 cM) on chromosome 17 in 45 primary gastric cancers (GCs). The data indicated the presence of tumor suppressor genes (TSGs) on chromosome 17 involved in GC. Among the putative TSGs in these regions, HIC1 (in SR(1)) and TOB1 (in SR(3)) remain to be examined in GC. By immunohistochemistry (IHC), methylation-specific PCR (MSP) and western blot, we evaluated the expression and regulation status for HIC1 and TOB1 protein in GC. We narrowed down the deletion intervals on chromosome 17 and defined five smaller LOH subregions, SR(1)-SR(5) (0.54 to 3.42 cM), in GC. We found that HIC1 had downregulated expression in 86% (91/106) and was methylated in 87% (26/30) of primary GCs. Of the primary GCs showing downregulation of HIC1 protein, 75% (18/24) had methylated HIC1 gene. TOB1 was either absent or expressed at reduced levels in 75% (73/97) of the GC samples. In addition, a general reduction was found in total and the ratio of unphosphorylated to phosphorylated TOB1 protein levels in the differentiated GC cell lines. Further analysis revealed significant simultaneous downregulation of both HIC1 and TOB1 protein in GC tissue microarray samples (67%, 52/78) and in primary GCs (65%, 11/17). These results indicate that silencing of HIC1 and TOB1 expression is a common occurrence in GC and may contribute to the development and progression of the disease.
Molecules and Cells 04/2011; 32(1):47-55. · 2.18 Impact Factor
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ABSTRACT: Matrix metalloproteinases (MMPs) are one of the major classes of proteolytic enzymes involved in tumor invasion and metastasis, being inhibited by naturally occurring tissue inhibitors of metalloproteinases (TIMPs). We examined mRNA expression for MMP-2, MMP-7, MMP-9, MT1-MMP, TIMP-1, and TIMP-2 in human gastric adenocarcinoma tissues, and the correlation between their expression and clinicopathological variables.
Gastric tissue samples from 72 patients with gastric adenocarcinoma were available for this study. To determine mRNA expression for MMP-2, MMP-7, MMP-9, MT1-MMP, TIMP-1, and TIMP-2, semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR) was carried out on tumor and normal tissues, respectively.
Mean MMP-2, MMP-7, MMP-9, MT1-MMP, TIMP-1, and TIMP-2 mRNA expression in the gastric adenocarcinomas was significantly higher than in the normal tissue. In terms of the invasion of the tumor, lymph node metastasis, and tumor stage of gastric adenocarcinoma, the differences in MMP-2, MMP-7, MMP-9, and MT1-MMP mRNA expression levels were significant. MMP-2, MMP-7, MMP-9, MT1-MMP, TIMP-1, and TIMP-2 mRNA expression did not differ significantly in relation to histological type of gastric adenocarcinoma.
The correlation between the increased expression of MMP-2, MMP-7, MMP-9, and MTI-MMP and clinicopathological parameters reflects a role in predicting the aggressive behavior of gastric cancer.
Journal of Surgical Oncology 03/2011; 103(3):243-7. · 2.10 Impact Factor
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ABSTRACT: Reports of clinicopathological features and prognosis in patients with signet ring cell carcinoma of the stomach (SRC) are conflicting. The aim was to describe the clinicopathological features and prognosis of patients with SRC in comparison with non-signet ring cell carcinoma of the stomach (NSRC).
In this retrospective study, we reviewed the records of 1,439 consecutive patients diagnosed with gastric carcinoma who were resected surgically from 1993 to 2003. Among them, 218 patients (15.1%) with SRC were compared with 1,221 patients with NSRC.
There were significant differences in tumor size, tumor location, macroscopic type, depth on invasion, lymph node metastasis, lymphatic invasion, tumor stage, chemotherapy, and curability between the patients with SRC histology and NSRC. The overall 5-year survival of patients with SRC was 44.9% as compared with 36.0% for patients with NSRC (P = 0.013). Multivariate analysis showed that lymph node metastasis and curative resection were significant factors affecting survival. A significant survival benefit for curative resection was observed, with a 5-year survival rate of 58.5% compared with non-curatively resected cases (8.4%).
When stage matched, SRC patients had a similar survival to NSRC patients. Curative resection is recommended to improve the prognosis of patients with SRC.
Journal of Gastrointestinal Surgery 04/2010; 14(4):601-6. · 2.83 Impact Factor
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ABSTRACT: Although the prognosis of stage IV gastric cancer is poor, some patients with stage IV gastric cancer had a long-term survival after gastrectomy. The objective of this study was to subclassify stage IV gastric cancer according to survival differences, evaluate the prognosis by substage, and identify the factors associated with patient survival in each substage.
The data from 1,176 patients who underwent gastric resection for stage IV gastric cancer between 1988 and 2007 at Tumor Hospital of Harbin Medical University were reviewed retrospectively. The patients were divided into three substages according to the survival differences: stage IVa (T1-2N3M0), stage IVb (T3N3M0 and T4N1-2M0), and stage IVc (T4N3M0 and TanyNanyM1). The clinicopathological characteristics as well as survival of the patients were evaluated retrospectively by substage.
There were no significant differences in survival among T3N3M0, T4N1M0, and T4N2M0 groups (p = 0.884) and between T4N3M0 and TanyNanyM1 groups (p = 0.192). The 5-year survival rates in stage IVa (T1-2N3M0), stage IVb (T3N3M0 and T4N1-2M0), and stage IVc (T4N3M0 and TanyNanyM1) were 22.7%, 9.9%, and 2.2%, respectively (p < 0.001). Multivariate analysis showed the following independent prognostic factors for survival: subclassification, operation type, number of retrieved lymph nodes, curability, and chemotherapy for stage IV gastric cancer; curability, chemotherapy, and number of retrieved lymph nodes for stage IVa and IVb; chemotherapy and operation type for stage IVc. For 406 patients with curative resection in stage IVa and IVb, hematogenous recurrence (35.9%) was the dominant recurrence pattern in stage IVa, whereas the most common patterns of recurrence were peritoneal (40.8%) and locoregional recurrence (31.8%) in stage IVb.
Subclassification of stage IV gastric cancer into IVa (T1-2N3M0), IVb (T3N3M0 and T4N1-2M0), and IVc (T4N3M0, TanyNanyM1) may be helpful to predict the outcome and determine the therapeutic strategies for patients with stage IV gastric cancer.
Journal of Gastrointestinal Surgery 12/2009; 14(3):484-92. · 2.83 Impact Factor
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ABSTRACT: The classification of lymph node metastasis in patients with gastric cancer is still controversial. Our aim was to evaluate the relative merits of four staging systems of lymph node metastasis.
In our study, the nodal status was classified according to the 5th edition of the tumor node metastasis (TNM) system, the Japanese Classification of Gastric Carcinoma (JCGC), the ratio of metastatic lymph nodes, and the size of the largest metastatic lymph node. Each staging system was scored as good (+2), fair (+1), or poor (0) with respect to the theoretical value (extent of the anatomical lymphatic tumor spread), convenience (simplicity), surgical applicability (extent of lymph node dissection), and prognostic value (ability to predict survival rate).
In the multivariate analysis including the four staging systems and other potential prognostic factors, stepwise Cox regression revealed that the ratio of metastatic lymph nodes was the most independent prognostic factor. The TNM, ratio, and size systems were convenient because they had no consideration for the location of the tumor and lymph node. Although the JCGC system had advantages in theoretical value and surgical application, it was most optional due to the complexity of the system.
Although all different staging systems are comparable, the metastatic lymph node ratio system is convenient, reproducible, and has the highest ability to predict survival.
World Journal of Surgery 09/2009; 33(11):2383-8. · 2.36 Impact Factor
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ABSTRACT: To study the expression of cyclooxygenase-2 (COX-2) gene in breast cancer and its clinicopathologic characteristics.
With beta-actin gene as reference, the COX-2 mRNA was monitored in 30 specimens of breast cancer tissue and adjacent normal breast tissue by reverse transcription-polymerase chain reaction (RT-PCR).
The COX-2 mRNA expression was significantly upregulated in most breast cancer tissues with range of 0.05 - 0.91 (median 0.56), which was rare in normal breast tissue with range of 0 - 0.09 (median 0). The difference of COX-2 mRNA expression between cancer and normal breast tissue was significant (rank sum test, P < 0.05). COX-2 overexpression in breast cancer was related to its lymph node metastasis (P < 0.05) but not to age, tumor size, pathologic grade or pathologic type (P > 0.05).
The level of COX-2 mRNA expression is obviously higher in the breast cancer tissue than that in normal breast tissue. COX-2 overexpression may play a crucial role in the carcinogenesis, development of cancer and lymph node metastasis in breast cancer patients.
Zhonghua zhong liu za zhi [Chinese journal of oncology] 12/2002; 24(6):567-9.
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ABSTRACT: This study gives insight into survival predictors and clinicopathological features of carcinoma of the gastric cardia.
The study included 233 patients who underwent operation for carcinoma of the gastric cardia. Clinicopathological prognostic variables were evaluated as predictors of long-term survival by univariate and multivariate analysis. Cox regression was used for multivariate analysis and survival curves were drawn by the Kaplan- Meier method.
Carcinoma of the gastric cardia was characterized by positive lymph node metastasis (77.3%), serosal invasion (83.3%) and more stage III or IV tumors (72.5%). Overall 5-year survival rate was 21.9% and median survival period was 24 months. The 5-year survival rate was influenced by tumor size, depth on invasion, lymph node metastasis, extent of lymph node dissection, disease stage, operation methods and resection margin.
The absent of serosal invasion and lymph node metastasis, curative resection should be considered to be the favourable predictors of long-term survival of patients with carcinoma of the gastric cardia.
Hepato-gastroenterology 59(115):930-3. · 0.66 Impact Factor
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ABSTRACT: The accurate diagnosis of lymph node metastasis is necessary in gastric cancer. This study was carried out to identify the risk factors of lymph node metastasis by extreme analysis.
Data from 77 patients with lymph node-positive small gastric cancer and 128 patients with lymph node-negative large gastric cancer were collected. The relationship between the two groups was compared, based on the clinical, pathologic, and preoperative clinical laboratory analysis findings. The independent risk factors influencing lymph node metastasis were determined by multiple logistic regression analysis.
Rural residence, introversive personality, low third gastric cancer, low serum fibrinogen content, serosal invasion, and high serum CEA level were found to be associated with lymph node metastasis. The rural residence, introversive personality, serosal invasion, and high serum CEA level were the independent risk factors for lymph node metastasis in the multivariate logistic regression model.
Rural residence, introversive personality, serosal invasion, and high serum CEA level were significantly and independently related to lymph node metastasis. The limited surgery with potentially incomplete lymph node dissection is not recommended in gastric cancer patients with these risk factors.
Hepato-gastroenterology 57(98):362-6. · 0.66 Impact Factor
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ABSTRACT: Although many authors investigate the prognostic factors of gastric cancer, there are few comprehensive studies on the surgical results and prognostic factors in patients with gastric cancer with peritoneal metastasis. The aim was to describe the clinicopathological features and prognosis of patients with gastric cancer with peritoneal metastasis.
We reviewed the records of 172 consecutive patients diagnosed as having primary gastric cancer with peritoneal metastasis from January 1997 to June 2004. Clinicopathologic prognostic variables were evaluated as predictors of long-term survival by univariate and multivariate analysis.
The tumors were characterized by positive lymph node metastasis (93.0%). The 1-year survival rate of patients was 19.3%, and median survival period was 16 months. The 1-year survival rate was influenced by lymph node metastasis, surgery methods, and chemotherapy. Of these, independent prognostic factors were lymph node metastasis (present vs. absent, relative risk 1.671, p = 0.005) and resection (no vs. yes, relative risk 1.402, p = 0.013).
Lymph node metastasis and resection emerged as two independent prognostic factors for long-term survival in patients with gastric cancer with peritoneal metastasis. Palliative resection of the primary tumor is important for appraising the prognosis of patients with gastric cancer with peritoneal metastasis.
Hepato-gastroenterology 57(101):997-1000. · 0.66 Impact Factor
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ABSTRACT: The prognostic factors and surgical management of gastric cancer invading adjacent organs remains controversial. The aim was to provide valuable prognostic and surgical information on patients with gastric cancer invading adjacent organs.
The retrospectively study included 367 patients who underwent gastric resection for gastric cancer invading adjacent organs. Clinicopathologic variables were evaluated as predictors of long-term survival by univariate and multivariate analyses. Multivariate analysis was performed using Cox's proportional hazards model.
The five-year survival rate was 10.1%, and median survival period was 14 months. The five-year survival rate was influenced by histologic type, lymph node metastasis, liver metastasis, peritoneal dissemination, extent of lymph node dissection and curability of operation. Of these, independent prognostic factors were lymph node metastasis (N2, N3 versus N0, N1, relative risk 2.028, P < 0.001), liver metastasis (present versus absent, relative risk 1.582, P= 0.023) and curative resection (no versus yes, relative risk 1.719, P < 0.001). A significant survival benefit for curative resection was observed with a five-year survival rate of 21.5% compared with non-curatively resected cases (5.1%).
In patients with gastric cancer invading adjacent organs, three independent prognostic factors were lymph node metastasis, liver metastasis, and curative resection. For patients with gastric cancer invading adjacent organs, we recommend performing combined organ resection in patients with locally advanced gastric carcinoma regardless of curability.
ANZ Journal of Surgery 80(7-8):510-4. · 1.25 Impact Factor
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ABSTRACT: To investigate the significance of pathological factors for formation, molecular characterization and prognosis of free gastric cancer cells in the peritoneal cavity.
The peritoneal lavage fluid of 132 patients with gastric cancer (invasion depth < or =T3) was sampled at laparotomy. The detection of free gastric cancer cells was performed by peritoneal lavage cytology (PLC) and detection of cytokeratin 18 (CK18) by immunocytochemistry. The relationship between positive rate of free gastric cancer cells and clinical features was analyzed. The expression of HGF, SP1, VEGF and CD34 were detected in 80 gastric cancer specimens with serosal invasion by immunohistochemistry. Clinical follow-up was performed for all the patients.
The positive rate of free gastric cancer cells by the combination of PLC and immunocytochemistry techniques correlated with tumor size, Borrmann type, differentiation, area, growing pattern, lymph node metastasis and serosal type, but it was not correlated to gender, tumor location, and Lauren type. Positive correlation was observed between microvessel density (MVD) and the expressions of HGF, SP1 and VEGF. The expressions of HGF, SP1 and VEGF and MVD werecorrelated with the clinicopathologic parameters. Single factor analysis showed that the relapse rate of patients receiving gastric cancer radical correction within half a year correlated with the expressions of HGF, SP1 and VEGF, MVD, positive PLC and tumor size.
The combination of PCL and CK18 detection for free gastric cancer cells is sensitive and specific. The positive rate of free gastric cancer cells, expressions of HGF, SP1, VEGF, and MVD correlated with the clinical and pathological factors of gastric cancer. The detection of some relative factors may help to evaluate the stage, and predict the presence of free gastric cancer cells and post-operation relapse.
Hepato-gastroenterology 56(91-92):891-8. · 0.66 Impact Factor
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ABSTRACT: The Wnt/beta-catenin signaling pathway is tightly regulated and has important functions in development, tissue homeostasis, and regeneration. Deregulation of Wnt/beta-catenin signaling is frequently found in various human cancers. This study evaluated the relationship between the expression of Wnt-1, beta-catenin and E-cadherin in gastric cancer and gastric cancer clinicopathological characters.
The cancerous tissues from 180 gastric cancer patients and the adjacent normal tissues from 30 gastric cancer patients hospitalized in our hospital from Jan 2000 to June 2001 were collected. The immunohistochemical SP method was carried out to detect Wnt-1, beta-catenin and E-cadherin. The pathological stage of gastric cancer was evaluated in hematoxylin-eosin staining by the same pathologist.
In the gastric cancerous tissues, the expression percentage of Wnt-1, beta-catenin and E-cadherin is 54.4%, 45.6%, 47.2%, respectively, which is significantly higher than the percentage expression of these genes in normal tissues (p<0.01). The expression levels of these three genes are significantly related to tumor size, tumor invasive depth, lymph node metastasis, pTNM stage, differentiation and five-year survival rate.
Wnt-1, beta-catenin and E-cadherin play an important role in the differentiation, progression, invasion and metastasis in gastric cancer; they are good indicators for evaluating the biological behaviors of gastric cancer. And also, they will be promising targets for developing anti-cancer drug in gastric cancer.
Hepato-gastroenterology 55(84):1126-30. · 0.66 Impact Factor
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ABSTRACT: To improve the treatment results for large gastric carcinoma, it is important to know the characteristics of long-term survivors. The aim of this study was to analyze the clinicopathological features of large gastric carcinoma patients and clarify the prognostic factors associated with long-term survival.
Between December 1996 and December 2002, a total of 334 patients entered the study. They underwent surgery for gastric carcinomas measuring 10cm or more in diameter. We examined 12 clinicopathological factors associated with the patient, tumor and surgery. Multivariate analysis was performed using Cox's proportional hazards model.
The 5-year survival rate was influenced by the extent of lymph node dissection, histological type, depth on invasion, lymph node metastasis, peritoneal dissemination, liver metastasis and disease stage. Of these, two independent prognostic factors were depth on invasion and lymph node metastasis.
Depth on invasion and lymph node metastasis emerged as two independent prognostic factors for the prediction of long-term survival in large gastric carcinoma patients. We can make a suitable treatment strategy for patients with gastric cancer through consideration of the prognostic factors.
Hepato-gastroenterology 58(112):2162-5. · 0.66 Impact Factor