Oncogenic and immunological role of EDIL3 in human tumours: From pan-cancer analysis to validation in gastric cancer.

Background: Epidermal growth factor-like repeats and discoidin I-like domains 3 (EDIL3) is a secreted extracellular matrix protein implicated in diverse physiological and pathological processes including embryonic development, angiogenesis, and anti-inflammatory responses. Recent reports have indicated that EDIL3 play critical roles in carcinogenesis and progression of many cancers. Herein, we performed a pan-cancer investigation to study the potential functions of EDIL3 in various cancers and experimentally validate its function in gastric cancer (GC). Methods: We analysed EDIL3 expression profiles in different tumours using The Cancer Genome Atlas database. The Kaplan-Meier Plotter was used to investigate the prognostic value of EDIL3, while receiver operating characteristic curve was performed to analyze its diagnostic efficacy. Several bioinformatics tools were used to study the association between EDIL3 and promoter methylation, gene enrichment analysis, immune infiltration, immune-related genes, and drug sensitivity. Molecular biology experiments were conducted to validate the tumorigenic effects of EDIL3. Results: EDIL3 is variably expressed in different cancers and is closely associated with clinical outcomes. An inverse correlation between EDIL3 and DNA methylation has been observed in 13 cancers. Enrichment analysis indicated that EDIL3 is correlated with many cellular pathways such as extracellular matrix receptor interactions and focal adhesion. EDIL3 was tightly associated with immune infiltration and immune checkpoints. EDIL3 knockdown can promote GC calls apoptosis while preventing proliferation, migration, and invasion in vitro. Conclusion: EDIL3 is a promising prognostic, diagnostic, and immunological biomarker in various cancers, which could be applied as a new target for cancer therapy.

CLEC4D as a Novel Prognostic Marker Boosts the Proliferation and Migration of Gastric Cancer via the NF-κB/AKT Signaling Pathway.

Purpose: The functions of C-type lectin domain family 4 member D (CLEC4D), one member of the C-type lectin/C-type lectin-like domain superfamily, in immunity have been well described, but its roles in cancer biology remain largely unknown. Patients and Methods: This study aims to explore the role of CLEC4D in gastric cancer (GC). Bioinformatics preliminarily analyzed the expression of CLEC4D in gastric cancer. Immunohistochemical staining was used to detect the expression level and clinical pathological characteristics of CLEC4D in gastric cancer. The biological function of CLEC4D in gastric cancer cell lines was verified through in vitro and in vivo experiments. Results: In this study, CLEC4D expression was found to be markedly increased in gastric cancer (GC) tissues compared with matched normal gastric tissues, and high CLEC4D expression independently predicted unfavorable overall survival in patients with GC. Knockdown of CLEC4D markedly inhibited GC cell proliferation and migration. Mechanistically, CLEC4D knockdown deactivated the Akt and NF-κB signaling pathways in GC cells. Conclusion: Together, these results demonstrate that aberrantly increased CLEC4D expression promotes cancer phenotypes via the Akt and NF-κB signaling pathways in GC cells.

EDIL3 is a potential prognostic biomarker that correlates with immune infiltrates in gastric cancer.

Background: EDIL3, which contains epidermal growth factor-like repeats and discoidin I-like domains, is a secretory protein that plays an important role in embryonic development and various illnesses. However, the biological function of EDIL3 in gastric cancer (GC) is still unclear. The objective of this research was to explore the role and potential mechanism of EDIL3 in GC. Methods: In this study, we used the GEPIA, HPA, MethSurv, SMART, STRING, GeneMANIA, LinkedOmics TIMER, TIMER2.0, TISIDB, and RNAactDrug databases to comprehensively analyze the roles of EDIL3 in GC. To validate the in silico findings, EDIL3 expression was measured in our collected GC tissues. Meanwhile, several in vitro experiments were performed to test the function of EDIL3 in GC. Results: We found that EDIL3 was highly expressed in GC and associated with adverse clinical features. In vitro assays revealed that EDIL3 promoted the proliferation, migration, and invasion of GC cells. The functions of EDIL3 and co-expression genes were significantly associated with extracellular structure organization and matrix receptor interaction. EDIL3 expression was positively associated with numerous tumor-infiltrating immune cells and their biomarkers. Conclusion: This study determined that EDIL3 may function as an oncogene and is associated with immune infiltration in GC. EDIL3 could be used as a potential therapeutic target for GC.

Sonic Hedgehog/Gli1 Signaling Pathway Regulates Cell Migration and Invasion via Induction of Epithelial-to-mesenchymal Transition in Gastric Cancer.

Background: The aberrant activation of the Sonic hedgehog (Shh) signaling pathway is involved in progression of several types of cancer, including gastric cancer (GC). However, it remains uncertain whether it also plays a critical role in promoting cancer initiation and progression by inducing epithelial-to-mesenchymal transition (EMT) in GC. Thus, the aim of the present study was to determine whether the Shh pathway is involved in GC, and to investigate the function of the Shh pathway in the induction of EMT in GC. Materials and methods: The expression levels of Shh pathway members and EMT markers were examined in GC tissues by immunohistochemistry. The association between these factors and patient clinicopathological characteristics was analyzed. In addition, Gli-antagonist 61 (GANT61) was used to block Shh/Gli1 pathway activity, and recombinant Shh proteins (N-Shh) were used to activate the Shh pathway in GC cells. Wound healing and Transwell invasion and migration assays were performed to assess the effects of the Shh pathway on the migration and invasion of GC cells in vitro. Furthermore, western blot analysis was used to examine the changes in protein expression. Results: The results demonstrated that these Shh/Gli1 pathway members were upregulated in GC tissues, and that Gli1 upregulation was associated with tumor progression and a poor prognosis. Gli1 expression was negatively associated with E-cadherin (E-Cad) expression, and positively with Vimentin (VIM) expression in GC specimens. Further analysis revealed that when the Shh/Gli1 pathway was activated, the migratory and invasive abilities of GC cells were enhanced, and the expression levels of Gli1 and VIM were increased, while E-Cad expression was decreased. Opposite results were observed when the Shh/Gli1 pathway was blocked by GANT61. Conclusions: The present study indicated that the Shh/Gli1 pathway exhibits an abnormal activation pattern in GC with possible predictive and prognostic significance. The Shh/Gli1 pathway may promote the migratory and invasive potential of GC cells by inducing EMT. The Shh/Gli1 pathway can thus be considered as a potential therapeutic target for GC.

Clinical significance of Stathmin1 expression and epithelial-mesenchymal transition in curatively resected gastric cancer.

In our previous study, it was demonstrated that the Stathmin1 (STMN1) is overexpressed in gastric cancer (GC) and that its high expression level is associated with tumor invasion and metastasis. Epithelial-mesenchymal transition (EMT) has also been shown to be critically involved in GC invasion and metastasis. Certain studies have indicated that STMN1 may serve an important role in the EMT process. However, the association between STMN1 expression and EMT-associated markers, as well as clinicopathological characteristics of patients with GC, remains unclear. The aim of the present study was to investigate the clinicopathological significance and prognostic value of STMN1 and EMT-associated markers in GC. The expression of STMN1 and the EMT-associated proteins E-cadherin (E-Cad) and vimentin (VIM) were analyzed by immunohistochemistry in GC and adjacent non-tumorous tissues. Associations between the expression of these markers and clinicopathological parameters were analyzed. The association between STMN1 expression and EMT-associated markers was investigated in the GC cell lines BGC-803 and SGC-7901. The results revealed that STMN1 was expressed in 63.5% of the 167 GC tissues, which was significantly higher than the percentage observed in the adjacent non-tumorous tissues (P=0.003). The STMN1 expression was demonstrated to be positively associated with the VIM levels (P=0.001) and negatively associated with the E-Cad levels (P=0.022) in GC tissues. The STMN1 expression was associated with Lauren's Classification, invasion depth, lymph node metastasis and pathological Tumor-Node-Metastasis (pTNM) stage (P<0.05). In the univariate analyses, the high E-Cad expression was a positive prognostic indicator for overall survival, whereas the high STMN1 and VIM expression was a negative indicator. COX multiple regression analysis demonstrated that the pTNM stage [hazard ratio (HR) 1.912, 95% confidence interval (CI): 1.282-2.851, P=0.001] and E-Cad expression (HR 0.403, 95% CI: 0.249-0.650, P=0.000) were independent prognostic factors. It was also revealed that the expression level of E-Cad decreased, while the expression level of VIM increased by depleting STMN1 levels in GC cells. The present results suggest that the aberrant expression of STMN1 may promote tumor progression through EMT in GC.

Evaluating the clinical feasibility: The direct bisulfite genomic sequencing for examination of methylated status of protocadherin10 (PCDH10) promoter to predict the prognosis of gastric cancer.

OBJECTIVE: To elucidate the clinical significance of the methylated status of CpG site count of PCDH10 promoter in the survival prediction in gastric cancer (GC). METHODS: In the previous study, we demonstrated that the methylated CpG site count was significantly associated with the overall survival (OS) of GC patients by using the bisulfite genomic sequencing (BGS) with no less than five clones per sample. It was so complex and expensive for patients to undergo the BGS clones. In this study, we detected the different CpG site counts (hypermethylated and hypomethylated) of PCDH10 DNA promoter in GC samples of 471 patients by directly bisulfite genomic sequencing (D-BGS) without any clone. Furthermore, we evaluated the relationships between the methylated status of PCDH10 promoter and OS. RESULTS: Two hundred and fifty-seven of 471 (54.6%) GC patients were identified to present with PCDH10 promoter methylation by D-BGS. Patients who presented with 5 or more methylated CpG site counts of PCDH10 promoter had significantly poorer prognosis than patients who with less than 5 methylated CpG site counts of PCDH10 promoter (p= 0.039). With the multivariate survival analysis, we demonstrated that T stage, N stage and the hypermethylated CpG site counts of PCDH10 DNA promoter were the independent predictors of OS of GC patients. In addition, the hypermethylated CpG site counts of PCDH10 DNA promoter had smaller Akaike information criterion (AIC) and Bayesian information criterion (BIC) values than the other two independent predictors of the OS, indicating the hypermethylated CpG site counts of PCDH10 DNA promoter as the best prognostic predictor of GC. CONCLUSIONS: Our present findings suggested that the hypermethylated CpG site counts of PCDH10 DNA promoter for evaluating the prognosis of GC was reasonable by using the D-BGS.

Prognostic nutritional index predicts postoperative complications and long-term outcomes of gastric cancer.

AIM: To investigate the impact of prognostic nutritional index (PNI) on the postoperative complications and long-term outcomes in gastric cancer patients undergoing total gastrectomy. METHODS: The data for 386 patients with gastric cancer were extracted and analyzed between January 2003 and December 2008 in our center. The patients were divided into two groups according to the cutoff value of the PNI: those with a PNI ≥ 46 and those with a PNI < 46. Clinicopathological features were compared between the two groups and potential prognostic factors were analyzed. The relationship between postoperative complications and PNI was analyzed by logistic regression. The univariate and multivariate hazard ratios were calculated using the Cox proportional hazard model. RESULTS: The optimal cutoff value of the PNI was set at 46, and patients with a PNI ≥ 46 and those with a PNI < 46 were classified into PNI-high and PNI-low groups, respectively. Patients in the PNI-low group were more likely to have advanced tumor (T), node (N), and TNM stages than patients in the PNI-high group. The low PNI is an independent risk factor for the incidence of postoperative complications (OR = 2.223). The 5-year overall survival (OS) rates were 54.1% and 21.1% for patients with a PNI ≥ 46 and those with a PNI < 46, respectively. The OS rates were significantly lower in the PNI-low group than in the PNI-high group among patients with stages II (P = 0.001) and III (P < 0.001) disease. CONCLUSION: The PNI is a simple and useful marker not only to identify patients at increased risk for postoperative complications, but also to predict long-term survival after total gastrectomy. The PNI should be included in the routine assessment of advanced gastric cancer patients.

Prognostic value of the lymph node ratio in stage III gastric cancer patients undergoing radical resection.

OBJECTIVE: The aim of this study was to investigate the prognostic value of metastatic lymph node ratio (LNR) in patients having radical resection for stage III gastric cancer. METHODS: A total of 365 patients with stage III gastric cancer who underwent radical resection between 2002 and 2008 at Tianjin Medical University Cancer Institute and Hospital were analyzed. The cut-point survival analysis was adopted to determine the appropriate cutoffs for LNR. Kaplan-Meier survival curves and log-rank tests were used for the survival analysis. RESULTS: By cut-point survival analysis, the LNR staging system was generated using 0.25 and 0.50 as the cutoff values. Pearson's correlation test revealed that the LNR was related with metastatic lymph nodes but not related with total harvested lymph nodes. Cox regression analysis showed that depth of invasion and LNR were the independent predictors of survival (p<0.05). There was a significant difference in survival between each pN stages classified by the LNR staging, however no significant difference was found in survival rate between each LNR stages classified by the pN staging. CONCLUSIONS: The LNR is an independent prognostic factor for survival in stage III gastric cancer and is superior to the pN category in TNM staging. It may be considered as a prognostic variable in future staging system.

Prognostic value of number of examined lymph nodes in patients with node-negative gastric cancer.

AIM: To elucidate the potential impact of examined lymph nodes (eLNs) on long-term survival of node-negative gastric cancer patients after curative surgery. METHODS: A total of 497 node-negative gastric cancer patients who underwent curative gastrectomy between January 2000 and December 2008 in our center were enrolled in this study. Patients were divided into 4 groups according to eLNs through cut-point analysis. Clinicopathological features were compared between ≤ 15 eLNs group and > 15 eLNs group and potential prognostic factors were analyzed. The Log-rank test was used to assess statistical differences between the groups. Independent prognostic factors were identified using the Cox proportional hazards regression model. Stratified analysis was performed to investigate the impact of eLNs on patient survival in each stage. Overall survival was also compared among the four groups. Finally, we explored the recurrent sites associated with eLNs. RESULTS: Patients with eLNs > 15 had a better survival compared with those with eLNs ≤ 15 for the entire cohort. By the multivariate survival analysis, we found that the depth of invasion and the number of eLNs were the independent predictors of overall survival (OS) of patients with node-negative gastric cancer. According to the cut-point analysis, T2-T4 patients with 11-15 eLNs had a significantly longer mean OS than those with 4-10 eLNs or 1-3 eLNs. Patients with ≤ 15 eLNs were more likely to experience locoregional and peritoneal recurrence than those with > 15 eLNs. CONCLUSION: Number of eLNs could predict the prognosis of node-negative gastric cancer, and dissection of > 15 eLNs is recommended during lymphadenectomy so as to improve the long-term survival.

[Interim report of prospective clinical study of two different digestive tract reconstruction after total gastrectomy].

OBJECTIVE: To compare post-operative long-term complications and quality of life of two digestive reconstruction procedures after total gastrectomy. METHODS: A total of 109 gastric cancer patients in Tianjin Medical University Cancer Hospital from March 2012 to February 2013 were prospectively enrolled and randomly divided into functional jejunal interposition (FJI) group (52 cases) and Roux-en-Y (R-Y) group (57 cases). The post-operative complications, nutritional status, and the quality of life were compared between two groups. RESULTS: One, 3 and 6 months after operation, the incidence of R-S syndrome in FJI group was lower as compared to R-Y group[13% (6/45) vs. 37% (18/49), 3% (1/30) vs. 42% (14/33), 5% (1/21) vs. 48% (11/23), all P<0.01], while 3 months after operation, the incidence of reflux and heartburn in FJI group was higher[53% (16/30) vs. 21% (7/33), P<0.01; 37% (11/30) vs. 12% (4/33), P<0.05]. There were no significant differences in quality of life questionnaire QLQ-C30 between R-Y and FJI groups. QLQ-STO22 stomach module revealed in FJI group, the eating score was better, but reflux score was worse as compared to R-Y group 3 months after operation (all P<0.01). CONCLUSIONS: Functional jejunal interposition keeps intestinal continuity preserving and food duodenal passing, which is a reasonable digestive reconstruction procedure.

Effects of extended lymphadenectomy and postoperative chemotherapy on node-negative gastric cancer.

AIM: To investigate the effects of extended lymphadenectomy and postoperative chemotherapy on gastric cancer without lymph node metastasis. METHODS: Clinical data of 311 node-negative gastric cancer patients who underwent potentially curative gastrectomy with more than 15 lymph nodes resected, from January 2002 to December 2006, were analyzed retrospectively. Patients with pT4 stage or distant metastasis were excluded. We analyzed the relationship between the D2 lymphadenectomy and the 5-year survival rate among different subgroups stratified by clinical features, such as age, tumor size, tumor location and depth of invasion. At the same time, the relationship between postoperative chemotherapy and the 5-year survival rate among different subgroups were also analyzed. RESULTS: The overall 5-year survival rate of the entire cohort was 63.7%. The 5-year survival rate was poor in those patients who were: (1) more than 65 years old; (2) with tumor size larger than 4 cm; (3) with tumor located in the upper portion of the stomach; and (4) with pT3 tumor. The survival rate was improved significantly by extended lymphadenectomy only in patients with pT3 tumor (P = 0.019), but not in other subgroups. Moreover, there was no significant difference in survival rate between patients with and without postoperative chemotherapy among all of the subgroups (P > 0.05). CONCLUSION: For gastric cancer patients without lymph node metastasis, extended lymphadenectomy could improve the survival rate of those who have pT3-stage tumor. However, there was no evidence of a survival benefit from postoperative chemotherapy alone.

Overexpression of stathmin 1 is associated with poor prognosis of patients with gastric cancer.

Recently, stathmin 1 has been proposed to function as an oncogene based on some relevant studies in multiple types of human cancers. However, the role of stathmin 1 in gastric cancer carcinogenesis has not been elucidated yet. The aim of this study was to investigate the expression of stathmin 1 as well as its association with overall survival of gastric cancer patients. The expression of stathmin 1 was detected by real-time quantitative reverse transcription polymerase chain reaction and Western blotting in gastric cancer and adjacent nontumor tissues. In addition, stathmin 1 expression was analyzed by immunohistochemistry in paraffin samples from 210 primary gastric cancer patients. The expression levels of stathmin 1 mRNA and protein in gastric cancer tissues were both significantly higher than those in adjacent nontumor tissues. In addition, the expression of stathmin 1 is correlated with Lauren's classification, depth of invasion, lymph node metastases, and tumor node metastasis (TNM) stage (all P < 0.05). Univariate analysis showed that high stathmin 1 expression was associated with poor prognosis in gastric cancer patients (P = 0.040). Multivariate analysis demonstrated that only lymph node metastasis and TNM stage were the independent prognostic indicators for gastric cancer. Stathmin 1 expression status is not an independent prognostic factor for patients with gastric cancer. Further subgroup analysis revealed that stathmin 1 expression was significantly correlated with prognosis in diffuse type gastric cancer. This research showed that the stathmin 1 overexpression might play an important role in the pathogenesis and subsequent progression of gastric cancer. Stathmin 1 could also be a potential therapeutic target in gastric cancer, especially for diffuse type gastric cancer.

[Prognosis analysis of 310 patients with pathological stage pN3 gastric cancer].

OBJECTIVE: To investigate the clinicopathological characteristics and prognostic factors of patients with pathological stage pN3 gastric cancer. METHODS: A retrospective study of 310 patients with histologically confirmed pN3 stage gastric cancer undergoing radical gastrectomy from January 2000 to December 2006 in our department was performed. The Kaplan-Meier method was used to analyze the survival. Log-rank test and Cox regression model were carried out for univariate and multivariate analyses. RESULTS: All the patients were followed up for 2 to 103 (mean 35.7) months. The overall 5-year survival rate was 14.6%. There were 201 cases with stage pN3a and 109 cases with stage pN3b, and the 5-year survival rates were 16.8% and 10.3% respectively (P=0.013). Univariate analysis showed that tumor location, Borrmann type, depth of tumor invasion, surgical method, metastatic lymph node ratio, and pN stage were associated with postoperative survival (all P<0.05). The multivariate analysis revealed that depth of tumor invasion, surgical method and metastatic lymph node ratio were independent prognostic factors, while the pN stage was not. The difference of 5-year survival rate between pN3a and pN3b subgroups was significant in pT4a patients (16.1% vs. 12.8%, P=0.001), while such difference was not significant in pT4b patients (8.6% vs. 3.1%, P=0.137). CONCLUSIONS: Prognosis of patients with pN3 stage gastric cancer after radical resection is poor. Depth of tumor invasion and surgical method are independent prognostic factors for pN3 stage gastric cancer. Metastatic lymph node ratio is valuable to predict the prognosis of pN3 stage patients. The pN3 staging of the 7th UICC provides a more accurate prediction of prognosis.

Validity and necessity of sub-classification of N3 in the 7th UICC TNM stage of gastric cancer.

BACKGROUND: The 7th TNM staging is the first authoritative standard for evaluation of effectiveness of treatment of gastric cancer worldwide. However, revision of pN classification within TNM needs to be discussed. In particular, the N3 sub-stage is becoming more conspicuous. METHODS: Clinical data of 302 pN3M0 stage gastric cancer patients who received radical gastrectomy in Tianjin Medical University Cancer Institute and Hospital from January 2001 to May 2006 were retrospectively analyzed. RESULTS: Location of tumor, depth of invasion, extranodal metastasis, gastric resection, combined organs resection, lymph node metastasis, rate of lymph node metastasis, negative lymph nodes count were important prognostic factors of pN3M0 stage gastric cancers. TNM stage was also associated with prognosis. Patients at T2N3M0 stage had a better prognosis than other sub-classification. T3N3M0 and T4aN3aM0 patients had equal prognosis which followed the T2N3M0. T4aN3bM0 and T4bN3aM0 had lower survival rate than the formers. T4bN3bM0 had worst prognosis. In multivariate analysis, TNM stage group and rate of lymph node metastasis were independent prognostic factors. CONCLUSIONS: The sub-stage of N3 may be useful for more accurate prediction of prognosis; it should therefore be applied in the TNM stage system.

[Clinicopathological characteristics and prognostic analysis of bone metastasis in gastric cancer patients].

OBJECTIVE: To investigate the clinicopathological characteristics and prognostic factors of bone metastasis in gastric cancer patients. METHODS: Clinicopathological data of 66 gastric cancer patients with bone metastasis, who were treated at the Tianjin Medical University Cancer Institute and Hospital from October 1997 to September 2011, were analyzed retrospectively. The clinicopathological characteristics of the primary cancer and bone metastasis were summarized and the prognosis was analyzed. RESULTS: Of 66 patients, 4 underwent operation, 28 chemotherapy, 32 inhibitors of bone resorption,8 local treatment and 23 symptomatic treatment alone. The median survival time of these 66 patients was 5 months (95%CI:3.3-6.7 months). The 1-, 2- and 3-year survival rates were 9.1%, 3.0% and 1.5%, respectively. Univariate Log-rank test indicated that gender, bone metastasis combined with other distant metastasis and chemotherapy were significant prognostic factors (all P<0.05). Multivariate analysis revealed bone metastasis combined with other distant metastasis was an independent prognostic factor (P=0.011, RR=2.067, 95%CI:1.178-3.626). CONCLUSIONS: Prognosis of patients with bone metastasis from gastric cancer is poor. Chemotherapy-based comprehensive treatment may improve the prognosis of these patients.

[Treatment and prognostic analysis of early stage of primary gastric diffuse large B-cell lymphoma].

OBJECTIVE: To explore the prognostic factors and to compare chemotherapy alone versus surgical resection plus chemotherapy for early stage primary gastric diffuse large B-cell lymphomas (DLBCL). METHODS: Clinical data of 75 patients who were diagnosed as primary gastric DLBCL between January 1993 and August 2008 in Cancer Institute and Hospital of Tianjin Medical University were reviewed retrospectively. RESULTS: Among these 75 patients, 20 patients received chemotherapy alone and 55 underwent surgical resection plus chemotherapy. Complete remission rates were 65.0% (13/20) and 83.6% (46/55), effective rates were 75.0% (15/20) and 92.7% (51/55), and 5-year survival rates were 86.9% and 78.7% respectively in chemotherapy alone group and resection plus chemotherapy group, while the differences were not statistically significant (all P>0.05). Multivariate Cox regression model showed that international prognosis index (IPI) was the only independent prognostic factor (P<0.05, HR=11.350, 95%CI:1.011-127.371). CONCLUSIONS: In early stage of DLBCL, IPI is the only independent prognostic factor. The clinical outcomes are comparable between chemotherapy alone and surgical resection plus chemotherapy.

[Prognostic analysis of 280 patients with T4a gastric cancer who underwent curative resection].

OBJECTIVE: To evaluate the predicators of survival and recurrence after curative resection for gastric cancer patients with serosal invasion. METHODS: Clinical and follow-up data of 280 patients with T4a gastric cancer(according to the 7th UICC TNM Classification for gastric cancer) who underwent curative resection for gastric cancer between January 1997 and December 2003 were analyzed retrospectively. RESULTS: Five-year survival rate of these 280 patients was 50.0% and 158 patients (56.4%) presented with recurrence after surgery. The 3-year disease-free survival rate was 57.5%. The number of lymph node metastasis and metastatic lymph node ratio(MLR) were identified as the independent predicators for overall survival(P<0.05). The extent of lymph node metastasis was identified as the independent predicators for disease free survival (P<0.05). The extent of lymph node metastasis, the number of lymph node metastasis, and MLR were identified as the independent predicators for recurrence after surgery(P<0.05). CONCLUSIONS: The number of lymph node metastases, extent of lymph node metastasis and MLR are independent predictors of overall survival and recurrence in T4a gastric cancer patients after curative resection.

[A retrospective analysis of clinic-pathological characteristics and prognostic factors for 204 cases of primary gastric lymphoma].

OBJECTIVE: To explore the clinicopathological characteristics and prognostic factors of primary gastric lymphoma (PGL). METHODS: The clinical data of 204 patients with PGL was reviewed and analyzed. There were 106 males and 98 females, their age were 19 to 85 years (average age was 53.7 years). The Focal areas included gastric fundus lesions 41 cases (20.1%), stomach body lesions 127 cases (62.3%), distal gastric lesions 105 cases (51.5%), cardia lesions 13 cases (6.4%), duodenal bulb lesion 1 cases (0.5%). The clinical characteristics and the outcomes in patients with influence were analysed. RESULTS: In 204 PGL patients, the most common complaints were abdominal pain (62.3%) and weight loss (52.9%). Most of the PGL patients appeared ulcerative (76.0%) and results showed that 62.7% patients involved single location. As to the factors of cellulate grading and pathological characteristics, most patients (87.7%) show low-grade or intermediate-grade lymphoma, Musshoff stages I and II (74.0%). In 186 patients with complete follow-up data, survival rates of 1-, 3- and 5-year were 75.8%, 63.4% and 60.2% respectively. The median overall survival time was 50.0 months. In univariate survival analysis, age (χ(2) = 5.030), level of LDH (χ(2) = 40.084), cellulate grading (χ(2) = 35.238), Musshoff stage (χ(2) = 71.601), tumor diameter (χ(2) = 12.018) and option of managements (χ(2) = 14.140) were obviously correlated with the prognosis (all P < 0.05). Musshoff stage (RR = 2.230, 95%CI: 1.372 - 3.625) and cellulate grading (RR = 1.892, 95%CI: 1.010 - 3.543) were independent prognostic factors in multivariable analysis (both P < 0.05). There was no prognostic difference between surgery and chemotherapy in stage I and II (χ(2) = 1.223, P = 0.542). CONCLUSIONS: Musshoff stage and grade malignancy are independent prognostic factors. For patients with stage I and II, surgical resection is not the first-choice for clinical therapy.

[Risk factors for early recurrence after radical resection of proximal gastric cancer].

OBJECTIVE: To explore the risk factors for early recurrence (recurrence within 2 years) of proximal gastric cancer after radical resection. METHODS: The clinical data of 367 proximal gastric cancer patients who underwent radical resection in the Cancer Institute and Hospital of Tianjin Medical University between January 2000 and May 2006 were reviewed. Among them, there are 71 patients (19.3%) with early recurrence. Univariate analysis and multivariate analysis were applied to investigate risk factors for early recurrence. RESULTS: Univariate analysis showed that Borrmann type (P<0.01), histology type (P<0.01), depth of invasion (P<0.05), negative lymph nodes count (P<0.05) were risk factors for early recurrence of proximal gastric. On multivariate analysis, histology type (P<0.05), depth of invasion (P<0.05), negative lymph nodes counts (P<0.05) were independent risk factors for early recurrence of proximal gastric cancer. Negative lymph nodes in early recurrence patients were 8.4 ± 7.2, which were significantly less as compared to patients without early recurrence (10.7 ± 8.7) (P<0.05). CONCLUSION: For T3 proximal gastric adenosquamous cancer, extended resection and lymphadenectomy should be considered. Intraoperative or postoperative adjuvant treatment should be administered as routine.

[Use of uncut Roux-en-Y reconstruction after distal gastrectomy for gastric cancer].

OBJECTIVE: To evaluate the clinical efficacy of uncut Roux-en-Y reconstruction after distal gastrectomy for gastric cancer. METHODS: Clinical data of 419 patients who underwent distal gastrectomy for gastric cancer with complete follow-up data between March 2005 and March 2008 in the Cancer Institute and Hospital of Tianjin Medical University. Patients were divided into B I (138 cases with Billroth I reconstruction), M-B II (108 cases with modified Billroth II reconstruction), RY (46 cases with Roux-en-Y reconstruction) and Uncut RY (127 cases with uncut Roux-en-Y reconstruction) according to reconstructive methods. RESULTS: Patients in the Uncut RY group had a larger tumor diameter, more T3, and poorer stage of disease compared to those in the B I (P<0.05). In Uncut RY group, the operative time and postoperative hospital stay were(132.6±19.2) minutes and (10.4±1.2) days respectively, shorter than those in RY group (142.5±11.7) minutes and (12.1±3.7) days(both P<0.05), alkaline reflex gastritis rate was 3.2%, lower than that in B I group (24.6%, P<0.05) and M-B II group (25.9%, P<0.05). Marginal ulcer rate in uncut RY group was lower compared to M-B II group (P=0.019), and incidence of Roux-en-Y stasis syndrome was less compared to RY group (P=0.000). CONCLUSIONS: The uncut Roux-en-Y reconstruction is both feasible and safe. It can prevent alkaline reflex gastritis and Roux-en-Y stasis syndrome. It may be the preferred technique for reconstruction after distal gastrectomy.